General Screening Research Articles

Selection of Leptin Surrogates by a General Phenotypic Screening Method for Receptor Agonists.

There is a high demand for agonist biomolecules such as cytokine surrogates in both biological and medicinal research fields. These are typically sourced through natural ligand engineering or affinity-based screening, followed by individual functional validation. However, efficient screening methods for identifying rare hits within immense libraries are very limited. In this research article, we introduce a phenotypic screening method utilizing biological receptor activation-dependent cell survival (BRADS). This method offers a high-throughput, low-background, and cost-effective approach that can be implemented in virtually any biochemical laboratory setting. As a proof-of-concept, we successfully identified a surrogate for human leptin following a two-week cell culture process, without the need for specialized high-throughput equipment or reagents. This surrogate effectively emulates the activity of native human leptin in cell validation assays. Our findings not only underscore the effectiveness of BRADS but also suggest its potential applicability to a broad range of biological receptors, including Notch and GPCRs.

Cancer prevention in people experiencing homelessness: ethical considerations and experiences from the CANCERLESS project.

The incidence of cancer in Europe has been increasing in recent years. Despite this, cancer prevention has remained a low priority in health policies. Cancer is one of the main causes of mortality among people experiencing homelessness, who continue to have difficulties accessing prevention programs. A strategy that has been tested to favor cancer prevention is the health navigator figure. The objective of CANCERLESS project is to implement this model among populations experiencing homelessness in four European countries to foster the prevention and early detection of cancer. In this perspective, a presentation of CANCERLESS project is made, and its ethical aspects are discussed according to the ethics of public health, the ethics of care, solidarity, relational autonomy, and the social recognition of the virtue of just generosity. The ethical foundations of CANCERLESS project are rooted in social justice and in equity in access to health systems in general and cancer screening programs in particular. The ethics of public health guided by utilitarianism are insufficient in serving the interests of the most disadvantaged groups of the population. Hence, it is necessary to resort to relational bioethics that includes the ethics of care and solidarity and that recognizes the moral identity of socially excluded persons, reaffirming their position of equality in society. Relational autonomy therefore provides a broader conception by including the influence of living conditions in decisions. For this reason, the CANCERLESS project opts for a dialogue with those affected to incorporate their preferences and values into decisions about cancer prevention.

Generalizability of Deep Neural Networks for Vertical Cup-to-Disc Ratio Estimation in Ultra-Widefield and Smartphone-Based Fundus Images.

To develop and validate a deep learning system (DLS) for estimation of vertical cup-to-disc ratio (vCDR) in ultra-widefield (UWF) and smartphone-based fundus images. A DLS consisting of two sequential convolutional neural networks (CNNs) to delineate optic disc (OD) and optic cup (OC) boundaries was developed using 800 standard fundus images from the public REFUGE data set. The CNNs were tested on 400 test images from the REFUGE data set and 296 UWF and 300 smartphone-based images from a teleophthalmology clinic. vCDRs derived from the delineated OD/OC boundaries were compared with optometrists' annotations using mean absolute error (MAE). Subgroup analysis was conducted to study the impact of peripapillary atrophy (PPA), and correlation study was performed to investigate potential correlations between sectoral CDR (sCDR) and retinal nerve fiber layer (RNFL) thickness. The system achieved MAEs of 0.040 (95% CI, 0.037-0.043) in the REFUGE test images, 0.068 (95% CI, 0.061-0.075) in the UWF images, and 0.084 (95% CI, 0.075-0.092) in the smartphone-based images. There was no statistical significance in differences between PPA and non-PPA images. Weak correlation (r = -0.4046, P < 0.05) between sCDR and RNFL thickness was found only in the superior sector. We developed a deep learning system that estimates vCDR from standard, UWF, and smartphone-based images. We also described anatomic peripapillary adversarial lesion and its potential impact on OD/OC delineation. Artificial intelligence can estimate vCDR from different types of fundus images and may be used as a general and interpretable screening tool to improve community reach for diagnosis and management of glaucoma.

Prevalence of gestational diabetes mellitus in Germany: Temporal trend and differences by regional socioeconomic deprivation.

Gestational diabetes mellitus (GDM) increases the risk for adverse pregnancy outcomes. In 2012, a general screening for GDM was introduced in Germany. The analysis is based on data from the external inpatient quality assurance for obstetrics from the years 2013 to 2021. Women with pregestational diabetes were excluded. GDM was defined either by documentation in the maternity record or by ICD diagnosis O24.4 during hospitalisation. We reported the prevalence stratified by year, maternal age and regional socioeconomic deprivation. The age-standardized prevalence of GDM continuously rose from 4.7 % in 2013 to 8.5 % in 2021. The increase was observed in all age groups. In 2021, this corresponded to 63,563 women with GDM. The prevalence was higher in highly deprived regions than in low deprived regions. A steady increase in GDM prevalence and evidence of health inequalities emphasise the need for primary prevention strategies for GDM.

Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea.

Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. We screened &gt;10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. The hazard ratio of death was significantly high in both the eGFR &lt;60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

ОСОБЕННОСТИ ПРЕПОДАВАНИЯ ДИСЦИПЛИНЫ ТОКСИКОЛОГИЧЕСКАЯ ХИМИЯ СТУДЕНТАМ, ОБУЧАЮЩИМСЯ ПО СПЕЦИАЛЬНОСТИ 32.05.01 МЕДИКО-ПРОФИЛАКТИЧЕСКОЕ ДЕЛО

The question of organizing the learning process for students of the medical and preventive faculty at the Institute of Pharmacy is significant for the teacher. Compared to students of the Faculty of Pharmacy, they do not have sufficient knowledge in chemistry, so it is necessary to search for additional teaching methods. After the transition to training according to the Bologna system, classroom lessons were reduced and student independent work was increased. The classroom load of students is 36 hours a week, leaving almost no time for independent work. Because students are poorly prepared in chemistry, instructors typically upgrade their knowledge to proficiency levels by providing preparatory materials in toxicological chemistry. According to the curriculum in toxicological chemistry, 42 contact-hours of work are allocated (10 hours of lectures + 32 hours of seminars and practical classes). How can a teacher at the Institute of Pharmacy motivate a medical student to study a medical discipline? One of the possible ways to increase interest in this way is through research work in a medical laboratory and, as an option, involving students in joint scientific work at university departments. The training was organized on the basis of lectures, seminars (round table) and practical exercises. The lectures covered only problematic and review material intended to test theoretical knowledge about compliance with remote disciplinary measures. At the Institute of Pharmacy of Kazakh State Medical University, the round table method was used when conducting seminars. Students go into the topic in advance. When preparing for employment, use scientific and professional information from a variety of sources. In practical classes, students acquired sample preparation skills for identifying toxic substances, developed skills in isolating toxic substances, and used chemical and instrumental methods of analysis. Students mastered modern physicochemical and chromatographic methods of analysis used in the system of general and private screening of chemical substances. During the last lesson, educational and research work is carried out. Based on the results of mastering the discipline, students of the Faculty of Preventive Medicine acquired a colossal amount of knowledge, which they will later use in practical work.

Lipid-Restricted Culture Media Reveal Unexpected Cancer Cell Sensitivities.

Cancer cell culture models frequently rely on fetal bovine serum as a source of protein and lipid factors that support cell survival and proliferation; however, serum-containing media imperfectly mimic the in vivo cancer environment. Recent studies suggest that typical serum-containing cell culture conditions can mask cancer dependencies, for example, on cholesterol biosynthesis enzymes, that exist in vivo and emerge when cells are cultured in media that provide more realistic levels of lipids. Here, we describe a high-throughput screen that identified fenretinide and ivermectin as small molecules whose cytotoxicity is greatly enhanced in lipid-restricted media formulations. The mechanism of action studies indicates that ivermectin-induced cell death involves oxidative stress, while fenretinide likely targets delta 4-desaturase, sphingolipid 1, a lipid desaturase necessary for ceramide synthesis, to induce cell death. Notably, both fenretinide and ivermectin have previously demonstrated in vivo anticancer efficacy despite their low cytotoxicity under typical cell culture conditions. These studies suggest ceramide synthesis as a targetable vulnerability of cancer cells cultured under lipid-restricted conditions and reveal a general screening strategy for identifying additional cancer dependencies masked by the superabundance of medium lipids.

Development of label-free triboelectric nanosensors as screening platforms for anti-tumor drugs

This study introduces a general label-free drug screening platform with potential to support high-throughput drug screening for any protein target. Its innovation lies in quantifying the affinity of molecule-molecule interactions via voltage output variation, which achieves unprecedented selectivity and sensitivity. It combines computational analysis complemented by experimental substantiation with a solid-liquid triboelectric nanosensor. Owing to its high binding affinity, FKBP-rapamycin is used as a model system to demonstrate the platform's sensitivity. Subsequently, the research is extended to study drug interactions with an oncogenic protein ATG4B. The findings unveil the binding of S130 and Tioconazole to ATG4B, a critical cysteine protease involved in autophagy, while revealing that Dexamethasone does not bind ATG4B. This binding exerts a specific inhibitory effect on autophagic flux and triggers cancer cell apoptosis. The results support the previously verified inhibitory effects of these drugs and the effectiveness of a newly developed self-powered drug screening platform, leveraging the principles of solid-liquid contact electrification. This approach adeptly confronts enduring challenges in traditional drug development methods where biochemical assays need to be designed for each individual protein target or only time-consuming and concentration-demanding molecular interaction measurements were made available.

Detection of Islet Autoantibodies in Whole Blood by Antibody Detection by Agglutination-PCR (ADAP) Technology Is Sensitive and Suitable for General Population Screening Programs

Background. Detection of type 1 diabetes (T1D) at the preclinical stage is possible by detecting islet autoantibodies (IAs) years before the appearance of symptomatic diabetes. The Antibody Detection Israeli Research is a general population screening program searching for children with multiple IAs who are at risk of developing T1D. IAs are measured in capillary or venous whole blood (WB) samples using the novel ultrasensitive antibody detection by agglutination-PCR (ADAP) technology. Objective. To assess the accuracy and reliability of the ADAP assay in venous and capillary WB. Materials and Methods. In total, 50 children with T1D and 50 healthy controls participated in the study. Venous and capillary blood samples were drawn from participants with T1D, while only venous blood was drawn from the controls. The ADAP assay in venous and capillary blood was compared to the currently used assays in their ability to detect glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), and insulin autoantibodies (IAAs). Results. The area under the curve using the receiver operating characteristic curves was comparable between the ADAP assay in WB and standard enzyme-linked immunosorbent assay (ELISA)/radioimmunoassay (RIA) for all three IAs GADA 0.946 (95% CI: 0.900–0.991) vs. 0.949 (0.906–0.992), P=0.873; IA-2A 0.747 (0.649–0.844) vs. 0.666 (0.587–0.744), P=0.106; IAA 1.000 (1.000–1.000) vs. 1.000 (1.000–1.000), P=1.000. The correlation between the levels of IA in venous and capillary WB using ADAP was R2 = 0.958 (P &lt;0.01), R2 = 0.943 (P &lt;0.01), and R2 = 0.711 (P &lt;0.01) for GADA, IA-2A, and IAA, respectively. IA levels in venous and capillary WB using ADAP were comparable without a proportional bias in Bland–Altman’s plots of agreement, suggesting the two methods may be used interchangeably. Conclusions. The ADAP assay is reliable in detecting IA in venous and capillary WB samples with comparable performance to standard RIA and ELISA. These findings open avenues for widespread use of the ADAP assay in future general population screening programs to detect children at risk of developing T1D.

Interesting case report on Chiari network

The Chiari network is a congenital remnant that is typically found in the right atrium and is generally not associated with significant pathophysiological implications. Usually, this is detected on general routine health checkup screening or casual examination. But, occasionally in certain cases, it is possible for this condition to results in diagnostic ambiguity when assessing right atrial disorders. Additionally, it has potential to contribute to the development of thromboembolism by inducing flow blockage. The Chiari network can be accurately diagnosed by echocardiography. This network appear as a highly mobile, highly reflectant echo target at many regions in the right atrium during transthoracic and transesophageal echocardiography. In this study, we provide a case involving an 18 year old male students studying cardiac technology who was diagnosed incidentally during echocardiography practical classes with Chiari network, mild TR and mild PR. The value and precision of echocardiography are becoming more widely recognized and being used more frequently. The potential for finding normal anatomical variations and their potential incorrect interpretation as pathological states coincides with the wider implementation of this imaging method.

DépistaFest: The evaluation of an inclusive, positive, and playful STBBI screening campaign's effectiveness.

Young adults are disproportionately affected by sexually transmitted and blood-borne infections (STBBIs), and rates of STBBI screening in this population are persistently low. The present study examined the effectiveness of Club Sexu's social marketing campaign, DépistaFest, in increasing STBBI screening, screening intentions, and general STBBI and STBBI screening knowledge among young adults in Quebec, Canada. Grounded in the health belief model, the campaign provided practical and scientifically accurate information on STBBIs and screening using an inclusive, positive, and playful approach. A sample of 686 participants (M = 28.0years old) was recruited through Club Sexu's social media to complete an online survey assessing campaign exposure, recent STBBI screening, screening intentions, and general STBBI and screening knowledge. Logistic regressions and ANCOVAs were performed to examine group differences on outcome variables. Compared to nonexposed participants, those who were exposed to the campaign were 2.11 times more likely to report having been tested in the past 6months, and 2.07 times more likely to report planning to get tested in the next 6months. Exposed participants were also more likely to correctly answer general STBBI knowledge questions and reported higher levels of self-perceived STBBI screening knowledge than nonexposed participants. The findings support the effectiveness of an STBBI prevention campaign grounded in the health belief model. Future STBBI prevention campaigns aimed at young adults would benefit from destigmatizing STBBIs and normalizing STBBI screening using an inclusive, positive, and playful approach.

Coupling thin layer chromatography with mass spectrometry for detection and identification of sertraline and its metabolite in the urine

The aim of the study was to detect sertraline and its metabolites in urine under standardized thin layer chromatography (TLC) screening conditions and identify the metabolites using the mass spectrometry method. Materials and methods. Urine samples, collected within 30 hours in portions of 20–50 mL, commenced from the seventh hour after the administration of a single therapeutic dose of the drug. The sample preparation process involved dilute acid hydrolysis, followed by the extraction of the native compound and metabolites with chloroform at a pH of 8–9. Thin layer chromatography studies of the extracts were conducted using four unified TLC systems recommended by The International Association of Forensic Toxicologists for general drug screening. Chromatograms were subjected to color reactions with a variety of chromogenic reagents. For the analysis of eluates from chromatograms, a Varian 1200 L mass spectrometer (Netherlands) equipped with a dual quadrupole mass analyzer was employed. Identification was performed through direct sample introduction into the ion chamber, electron-impact ionization (70 eV), and full ion scanning mode. Results. The spot of the native drug on the chromatogram was identified by the Rf, value. Metabolite of sertraline was identified as N-desmethyltrihydroxysertraline by the molecular ion peak in the mass spectrum. Conclusions. The study demonstrated the ability of TLC to detect sertraline and its metabolite, N-desmethyltrihydroxysertraline, in urine after the administration of a single therapeutic dose of the drug. The chromatographic mobility of the native compound and N-desmethyltrihydroxysertraline in the unified TLC screening systems, along with the results of their visualization using chromogenic reagents for toxicological drug screening, was determined. Furthermore, the potential of coupling TLC with mass spectrometry for the separation, detection, and confirmatory identification of sertraline and its metabolic products in urine was established.

Developing a General Population Screening Programme for Paediatric Type 1 Diabetes: Evidence from a Qualitative Study of the Perspectives and Attitudes of Parents

Introduction. With reliable tests and preventative treatments now available the United Kingdom has introduced a prototype population-based paediatric (ages 3–13) screening programme for type 1 diabetes (T1D). To aid its ethical and sustainable implementation this work explores parental views around the concept of this programme to determine how their involvement might be encouraged and supported. Research Design and Methods. Qualitative interviews were undertaken with 38 parents and the data were analysed using a purposely developed “Burden of Screening” framework, which presented the data within three domains describing the various elements of screening participation; pre-screening tasks designated to participants; factors influencing engagement with screening; and consequences of screening participation. Results. Regarding pre-screening tasks designated to participants, the importance of clear communication about the condition were apparent with parents expressing uncertainty of the benefits of screening against the potential anxiety engendered. In factors influencing their engagement with screening participants described their preference for less invasive testing techniques, the reassurance of structured support from healthcare professionals inherent within the programme, and the potential benefit of peer support. Regarding the consequences of screening participation parents described how a positive result might lead to overly protective behaviours, and anxiety from watching and waiting for the onset of symptomatic T1D. Conclusions. The benefits of T1D screening need to be clearly communicated to facilitate uptake. To this end the use of decision-support tools and better targeted educational materials should be explored. Post-testing, parents expressed preferences for peer support and access to psychological counselling.

Validation research of pressure decay test method for internal leakage detection of hydraulic cylinder

Leakage test is one of the acceptance tests to ensure hydraulic cylinder reliability. Under the consideration of economic and technical maturity conditions, the existing internal leakage detection methods may be difficult to achieve rapid screening. After research, the pressure decay test method is a common method of quickly testing hydraulic cylinders for internal leakage in the manufacturing industry. However, the validity of the pressure decay test method has not been theoretically verified, limiting the versatility of the method. This paper will theoretically validate the effectiveness of the pressure decay test method and provide important theoretical support for its use as a general rapid screening method for internal leakage, thereby improving the reliability and safety of hydraulic systems. Both simulation and experimental results show that there is a linear relationship between the pressure decay rate and the internal leakage rate. Especially for working pressures greater than 16 MPa, the pressure factor has an insignificant impact on the application of this method.

Rapid antibiotic screening based on E. coli apoptosis using a potentiometric sensor array

Phenotypic antimicrobial susceptibility testing enables reliable antibiotic screening but requires multiple strategies to identify each phenotypic change induced by different bactericidal mechanisms. Bacteria apoptosis with typical phenotypic features has never been explored for antibiotic screening. Herein, we developed an antibiotic screening method based on the measurement of antibiotic-induced phosphatidylserine (PS) exposure of apoptotic bacteria. Phosphatidylserine externalization of E. coli that can be widely used as an apoptosis marker for antibiotics with different antibacterial mechanisms was explored. A positively charged PS-binding peptide was immobilized on magnetic beads (MBs) to recognize and capture apoptotic E. coli with PS externalization. Apoptotic E. coli binding led to the charge or charge density change of MBs-peptide, resulting in a potential change on a magneto-controlled polymeric membrane potentiometric sensor. Based on the detection of apoptotic E. coli killed by antibiotics, antibiotic screening for different classes of antibiotics and silver nanoparticles was achieved within 1.5 h using a potentiometric sensor array. This approach enables sensitive, general, and time-saving antibiotic screening, and may open up a new path for antibiotic susceptibility testing.

Use of General Health Examination and Cancer Screening among People with Disability Who Need Support from Others: Analysis of the 2016 Comprehensive Survey of Living Conditions in Japan.

Research on preventive healthcare services among people with disability in Japan is scarce. This study aimed to (1) examine the relationship between disability and the use of general health examination (GHE) and cancer screening (lung, gastric, colorectal, breast and cervical cancer) and (2) explore the reasons for not using GHE. This cross-sectional study used secondary data from individuals aged 20-74 years (n = 15,294) from the Comprehensive Survey of Living Conditions of 2016. Binomial logistic regression analysis was conducted to examine the relationship between disability and non-participation in preventive services. In addition, a descriptive analysis was conducted to explore the reasons for non-participation in GHE. Consequently, disability was identified as an independently associated factor for non-participation in GHE (odds ratios (OR): 1.73; 95% confidence interval (95%CI): 1.14-2.62) and screening for colorectal (OR: 1.78; 95%CI: 1.08-2.94), gastric (OR: 2.27; 95%CI: 1.27-4.05), cervical (OR: 2.12; 95%CI: 1.04-4.32) and breast cancer (OR: 2.22; 95%CI: 1.04-4.72), controlling for confounding factors. The most dominant reason for non-participation was "I can go to see the doctor anytime, if I am worried (25/54, 46.3%)." Our findings imply the existence of disability-based disparity in preventive healthcare service use in Japan.

Management of Rumex dentatus L. in Vicia faba L. cultivations via Ononis vaginalis Vahl. As a potential bioherbicide

Biological control of undesirable weeds associated with crop cultivation is a sustainable approach that can reduce chemical herbicide dependence. The current study aimed to assess the bio-herbicidal potential of the donor species Ononis vaginalis Vahl. on germination efficiency as well as various growth and physiological parameters of the recipient species Rumex dentatus L., a major broad bean pest (Vicia faba L.). To assess the greatest inhibitory allelopathic effect on the recipient species in mixed (Rumex dentatus L. and Vicia faba L.) and pure cultures (each one separately), two experiments were conducted under laboratory conditions. A Petri dish experiment using O. vaginalis shoot aqueous extract (5%, 10%, 20%, and 40%) and a pot experiment using O. vaginalis shoot crude powder (1%, 2%, 5%, and 10%) were conducted to investigate its biological activity on some growth and physiological parameters of both crop and weed species. O. vaginalis underwent a general phytochemical screening that revealed a high production of allelochemicals, which are secondary metabolites and may have a function like that of natural herbicides. The result showed that the germination of V. faba seeds in both pure and mixed cultures was not significantly affected by low levels of O. vaginalis shoot aqueous extract treatments in pure and mixed cultures, in contrast, those recorded for R. dentatus gradually dropped as levels of O. vaginalis increased in both cultures. Results recorded a significant increase in total phenolics of V. faba shoots and roots under different treatments, except at the high concentrations of crude powder at the donor species level (5 and10%). A reduction in the total phenolic and flavonoid fractions was observed in R. dentatus roots under varying concentration treatments. Conversely, under high concentration treatments, flavonoids decreased in the roots of the mixed culture of R. dentatus but increased in the shoots. In conclusion, allelopathy can be used to suppress weeds in field crops. The study confirmed the use of O. vaginalis into current weed control techniques. O. vaginalis could be explored further for weed suppression in the field.

Glaucoma Screening Guidelines Worldwide.

Recommendations for glaucoma screening vary significantly from organization to organization, and while worldwide screening is currently not recommended, there is support in many organizations for screening at-risk subgroups of the general population. To summarize and compare current glaucoma screening protocols of major national and international, governmental, and non-governmental organizations. A general review of the major medical, and more specifically ophthalmic, organizations within North America, South America, Europe, Asia, and Africa was undertaken. Protocols from recent international and regional meetings were reviewed and summarized and a comparative analysis was employed to highlight differences between national and regional policies. In general, it was found that worldwide screening for glaucoma is currently of limited clinical utility and unlikely to be cost-effective. However, a more targeted approach is recommended by some major organizations, including the American Academy of Ophthalmology, the Pan-American Association of Ophthalmology, and the International Council of Ophthalmology in conjunction with a group of prominent ophthalmologists based in Sub-Saharan Africa recommend a targeted approach to screening specific populations that are deemed to be at higher risk of developing glaucoma. General population screening for glaucoma has been adopted as a recommendation by only a few organizations and only in specific situations. It is the screening of high-risk populations that has been demonstrated to be not only clinically useful in diagnosing and treating larger proportions of the general population benefiting from a higher positive-predictive value for screening protocols in these groups but also cost-effective. Further research is needed to create cost-effective protocols to successfully screen these high-risk populations for glaucoma using methods that are sufficiently sensitive and specific.

Application of advanced high resolution mass spectrometric techniques for the analysis of losartan potassium regarding known and unknown impurities

Recalls of medicinal products can cause supply bottlenecks. This is often due to the findings of unexpected impurities that pose a health risk to patients. A recent example is losartan potassium which was contaminated with azido-impurities. The choice of the analytical method determines which substances can be detected and thus controlled. In this study a combination of an untargeted screening approach for impurities and a targeted evaluation of high-resolution mass spectrometry data was applied to search for impurities not described so far, leaving out a precise quantification. Six losartan potassium samples were studied regarding known and unknown impurities and hence highlight the applicability and capability of the approach. For separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and an electrospray ionization in positive and negative mode for mass spectrometric detection was used. An information-dependent acquisition method was applied for the measurement of losartan potassium samples. The untargeted data evaluation using general unknown comparative screening revealed the presence of N-methyl-2-pyrrolidone (NMP) and another impurity from synthesis. The identity of NMP was corroborated by a spiking experiment and the amount was estimated by means of standard addition. A targeted data evaluation by generating extracted ion chromatograms resulted in finding of four additional impurities. Combined approaches like this are needed to detect and respond to changes in the quality of drugs precociously.

Impact of Smoking and Alcohol Consumption on Early-Onset Gastric Cancer Development in Young Koreans: A Population-Based Study.

Although smoking and alcohol consumption are known risk factors for gastric cancer (GC), studies assessing their effects on early-onset GC are limited. In this nationwide, population-based, prospective cohort study, we assessed the effects of smoking and alcohol consumption on early-onset GC in patients aged <50 years. We analyzed data of patients aged 20-39 years who underwent cancer and general health screening in the Korean National Health Screening Program between 2009 and 2012. We calculated the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for GC incidence until December 2020. We enrolled 6,793,699 individuals (men:women=4,077,292:2,716,407) in this cohort. The mean duration of follow-up was 9.4 years. During follow-up, 9,893 cases of GC (men:women=6,304:3,589) were reported. Compared with the aHRs (95% CI) of never-smokers, those of former and current-smokers were 1.121 (1.044-1.205) and 1.282 (1.212-1.355), respectively. Compared with the aHRs (95% CI) of non-consumers, those of low-moderate- and high-risk alcohol consumers were 1.095 (1.046-1.146) and 1.212 (1.113-1.321), respectively. GC risk was the highest in current-smokers and high-risk alcohol consumers (1.447 [1.297-1.615]). Interestingly, alcohol consumption and smoking additively increased the GC risk in men but not in women (Pinteraction=0.002). Smoking and alcohol consumption are significant risk factors for early-onset GC in young Koreans. Further studies are needed to investigate sex-based impact of alcohol consumption and smoking on GC incidence in young individuals.