Nevin Manimala

G Ital Cardiol (Rome). 2024 Nov;25(11):775-782. doi: 10.1714/4352.43387.

ABSTRACT

Long-lasting epidemiological studies showed that prevention of coronary artery disease (CAD) is highly feasible with the management of several conditions called “risk factors”, such as hypertension, cholesterol, smoking, etc. Nevertheless, risk stratification for primary prevention using a statistical combination of risk factors is suboptimal, as conventional risk factors are age-dependent, so that their treatment would be too late to be effective. Genetic risk stratification, built on the genetic variants linked to CAD, has the advantage of being embedded in DNA and then it is independent of age. The rapid advancement of DNA analysis techniques has made it possible to identify many variants and to produce easily a statistical combination of them to obtain a polygenic risk score (PRS). Prospective clinical trials based on risk stratification for CAD using the PRS have shown that statin therapy is associated with a higher reduction in cardiac events in the high genetic risk group compared with the low genetic risk group. A wide clinical use of the PRS, however, is presently not possible, basically due to the lack of a standard in production and validation of the PRS, but genetic risk stratification has the potential to revolutionize primary prevention.

PMID:39450457 | DOI:10.1714/4352.43387

Clin Exp Dent Res. 2024 Dec;10(6):e948. doi: 10.1002/cre2.948.

ABSTRACT

OBJECTIVE: This study investigated the effects of adding tricalcium silicate nanoparticles (TCSNp) to the universal G2 bond adhesive (G2BU) in self-etch (SE) mode on shear bond strength (SBS) to orthodontic brackets, cytotoxicity, and degree of conversion (DC).

MATERIAL AND METHODS: A total of 176 human teeth were divided into four groups based on TCSNp concentration in G2BU adhesive: 0% (control), 1%, 3%, and 5%. The G2BU adhesive consists of a hydrophilic primer (P) and a hydrophobic bonding agent (2B). TCSNp were added to the 2B component by mixing 0.1, 0.3, and 0.5 g of TCSNp with 9.9, 9.7, and 9.5 g of 2B, respectively. SBS was assessed after 24 h of water storage and 5000 thermocycles using a universal testing machine. Cytotoxicity was evaluated using the MTT assay on rat embryo fibroblast cells, and DC was measured using fourier-transform infrared spectroscopy. Statistical analysis included one-way ANOVA and Tukey’s post-hoc test, with significance set at p < 0.05.

RESULTS: After 24 h, mean SBS values were 15.58 MPa (control), 13.66 MPa (1% TCSNp), 15.99 MPa (3% TCSNp), and 12.04 MPa (5% TCSNp). After 5000 thermocycles, SBS values decreased to 12.91 MPa (control), 12.42 MPa (1% TCSNp), 11.11 MPa (3% TCSNp), and 10.21 MPa (5% TCSNp). ANOVA showed significant differences between groups (p < 0.05), except between the control and 3% TCSNp groups. Cell viability increased with higher TCSNp concentrations, with significant differences at 72 h between control and 5% TCSNp groups (p = 0.014). Mean DC values were 51.66% (control), 49.33% (1% TCSNp), 49.66% (3% TCSNp), and 48% (5% TCSNp). ANOVA indicated no significant differences between groups.

CONCLUSIONS: Adding TCSNp to G2BU in SE mode maintains clinically acceptable SBS levels and enhances cytocompatibility. Higher TCSNp concentrations may reduce SBS and DC slightly. Further studies are needed to evaluate long-term effects.

PMID:39450452 | DOI:10.1002/cre2.948

J Exp Bot. 2024 Oct 25:erae435. doi: 10.1093/jxb/erae435. Online ahead of print.

ABSTRACT

Nonhost resistance (NHR) is the most durable and robust form of innate immunity, with a surge of interest in crop improvement. Of the NHR genes identified against rice blast, a devastating disease caused by Magnaporthe oryzae, Arabidopsis PEN2 is indispensable for pre-penetration resistance against M. oryzae, while a consortium of genes orchestrates post-penetration resistance via lesser-known mechanisms. We identified M. oryzae-susceptible mosA (mthfr2 pen2-3) from a randomly mutagenized Arabidopsis pen2-3 population using forward genetics. Analysis of T-DNA inserted mthfr2 lines and pen2-3 complemented mosA lines enunciated that MTHFR2-dependent resistance to M. oryzae is independent of PEN2. MTHFR2-defective plants exhibited higher ROS accumulation and expression of SA-dependent defense markers. MTHFR2-ligand docking revealed that A55V nonsynonymous substitution in mosA altered ligand binding efficiency. This further affected the metabolomic profile of mosA, effectively allowing in vitro germination and development of M. oryzae conidia. Moreover, the loss of function mutation in mthfr2 (involved in 1C metabolic pathway) potentiated mosA immunity against Pst DC3000. In conclusion, our findings assert MTHFR2 as a positive modulator of NHR against M. oryzae. This work documents another layer of conserved yet divergent metabolomic defense in Arabidopsis regulated by folate-mediated 1C metabolism that has the potential to revolutionize crop improvement.

PMID:39450434 | DOI:10.1093/jxb/erae435

Am J Health Syst Pharm. 2024 Oct 25:zxae302. doi: 10.1093/ajhp/zxae302. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Clinical pharmacists are embedded into the care for patients admitted to internal medicine floors at Cleveland Clinic. The existing practice model utilized by the internal medicine pharmacy team had an uneven distribution of clinical activities among the various pharmacist roles. A study was completed to evaluate a potential adjustment to the pharmacy practice model. The objective of this study was to assess the type and quantity of clinical activities performed by each pharmacist role. These data were then utilized to evaluate the need for redistribution of care activities among the pharmacist roles and to determine the need for additional pharmacist full-time equivalents.

METHODS: From January to February 2023, data pertaining to the amount and type of clinical activities completed by the 9 internal medicine pharmacist roles was either manually collected or extracted from the electronic medical record. The data were then utilized to calculate a responsibility score for each role. Descriptive statistics were also calculated to assess the results.

RESULTS: Each pharmacist role cared for an average of 34.4 patients (minimum, 24.4; maximum, 57.7) during the study period. The average responsibility score for each pharmacist role was 309.8 (minimum, 237.5; maximum, 447.8).

CONCLUSION: On the basis of the data collected during the 4-week study period, a new pharmacy practice model was developed that incorporated 2 additional full-time equivalents. This model balanced patient care responsibilities among the pharmacist roles and moved the practice model from a location-based to a team-based coverage model.

PMID:39450432 | DOI:10.1093/ajhp/zxae302

Histopathology. 2024 Oct 25. doi: 10.1111/his.15353. Online ahead of print.

ABSTRACT

Myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukaemia (AML) are neoplastic haematopoietic cell proliferations that are diagnosed and classified based on a combination of morphological, clinical and genetic features. Specifically, the percentage of myeloblasts in the blood and bone marrow is a key feature that has historically separated MDS from AML and, together with several other morphological parameters, defines distinct disease entities within MDS. Both MDS and AML have recurrent genetic abnormalities that are increasingly influencing their definitions and subclassification. For example, in 2022, two new MDS entities were recognised based on the presence of SF3B1 mutation or bi-allelic TP53 abnormalities. Genomic information is more objective and reproducible than morphological analyses, which are subject to interobserver variability and arbitrary numeric cut-offs. Nevertheless, the integration of genomic data with traditional morphological features in myeloid neoplasm classification has proved challenging by virtue of its sheer complexity; gene expression and methylation profiling also can provide information regarding disease pathogenesis, adding to the complexity. New machine-learning technologies have the potential to effectively integrate multiple diagnostic modalities and improve on historical classification systems. Going forward, the application of machine learning and advanced statistical methods to large patient cohorts can refine future classifications by advancing unbiased and robust previously unrecognised disease subgroups. Future classifications will probably incorporate these newer technologies and higher-level analyses that emphasise genomic disease entities over traditional morphologically defined entities, thus promoting more accurate diagnosis and patient risk stratification.

PMID:39450427 | DOI:10.1111/his.15353

Emerg Med Australas. 2024 Oct 25. doi: 10.1111/1742-6723.14516. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the use and impact of pathology tests in patients who present to the ED with mental health-related complaints. The primary objective is to measure the proportion of patients undergoing pathology tests and assess whether these tests trigger a change in management.

METHODS: In this retrospective study, we reviewed all recorded mental health presentations to our regional ED between January and June 2021. Patient characteristics, pathology tests, subsequent change in management, treatment costs and time to Emergency Physician and Psychiatrist were extracted. Descriptive statistics and multivariate analysis were used to explore associations between variables of interest, ED length of stay (LOS) and change in management.

RESULTS: Of 37 900 ED visits, 1462 (3.9%) were mental health-related presentations. Pathology tests were conducted in 47.7% of cases, with 3% leading to a change in management. Pathology tests were associated with increased treatment costs (45% increase for blood tests, 17% for urine), and increased ED LOS (48%). Patients with coexisting medical conditions were three times more likely to have a change in management.

CONCLUSION: Pathology tests should be reserved for patients with high-risk features and based on clinical assessment. Strategic use of pathology tests could avoid unnecessary delays and costs, enhancing patient care in mental health-related ED presentations.

PMID:39450423 | DOI:10.1111/1742-6723.14516

Front Netw Physiol. 2024 Oct 10;4:1467180. doi: 10.3389/fnetp.2024.1467180. eCollection 2024.

ABSTRACT

INTRODUCTION: Statistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective.

METHODS: Preliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification.

RESULTS: As expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset.

DISCUSSION: This study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses.

PMID:39450419 | PMC:PMC11499088 | DOI:10.3389/fnetp.2024.1467180

Front Public Health. 2024 Oct 10;12:1432370. doi: 10.3389/fpubh.2024.1432370. eCollection 2024.

ABSTRACT

INTRODUCTION: Infectious diseases can spread rapidly in the globalized world, and the complex intersection of individual, social, economic, and cultural factors make it difficult to identify vulnerabilities in the face of pandemics.

METHODS: Therefore, this study aimed to identify vulnerability factors to infection and worse outcomes associated with COVID-19. This is a scoping review study of six databases that selected publications between 2019 and 2023, focusing on individual, social, and programmatic dimensions of vulnerability. The results were recorded in a spreadsheet and analyzed, considering the interrelationships among these dimensions.

RESULTS: A total of 45 articles were included in the review. Content analysis was conducted using the theoretical framework of health vulnerability, which divides vulnerability into individual, social, and programmatic dimensions. Race/ethnicity, homelessness, incarceration, socioeconomic level, food insecurity, and remote areas were classified as social dimensions. On the other hand, cancer, cardiovascular disease, HIV/AIDS, alcoholism, advanced age, obesity, mental disorders, diabetes, kidney disease, and pregnancy were classified as individual dimensions. None of the publications found explicitly mentioned programmatic vulnerabilities.

DISCUSSION: The research found that social vulnerabilities reinforce individual vulnerabilities, creating a vicious cycle. In addition, programmatic vulnerabilities reinforce this relationship. This study emphasizes that public policies should address these different dimensions of vulnerability. It suggests that this information should be incorporated into health surveillance and future decision-making to face new pandemics.

SYSTEMATIC REVIEW REGISTRATION: https://archive.org/details/osf-registrations-wgfmj-v1.

PMID:39450391 | PMC:PMC11499102 | DOI:10.3389/fpubh.2024.1432370

Front Public Health. 2024 Oct 10;12:1398980. doi: 10.3389/fpubh.2024.1398980. eCollection 2024.

ABSTRACT

BACKGROUND: In the contemporary landscape, college students have emerged as a demographic increasingly vulnerable to AIDS. Recognizing that heightened awareness and progressive attitudes toward HIV are pivotal in its prevention, this study was conceived with the intent to meticulously evaluate the level of HIV understanding amongst college students, gauge their sentiments toward people living with HIV (PLHIV), and scrutinize factors influencing these perceptions.

METHOD: This study used an anonymous online questionnaire to collect data through a cross-sectional survey. The sample size for the survey was 4,193 students from four colleges and universities in Xuzhou City, Jiangsu Province, China, covering a variety of demographic characteristics. The survey focused on students’ level of knowledge related to HIV and their attitudes toward PLHIV. The study used descriptive statistics to describe the demographic characteristics of the sample, chi-square tests to examine differences within categorical variables, and logistic regression to investigate the associations between knowledge levels and attitudes.

RESULTS: A total of 4,193 university students were surveyed, among whom the majority (96.85%) demonstrated a high level of knowledge related to AIDS. Moreover, 55.52% of the participants reported positive attitudes toward individuals with AIDS. The multiple regression analysis revealed that female students (OR = 0.49, p < 0.001), those enrolled in medical programs (OR = 1.56, p = 0.014), students of Han Chinese ethnicity (OR = 2.46, p = 0.009), and individuals with fewer romantic involvements (OR = 1.57, p < 0.001) possess greater HIV/AIDS awareness. Moreover, lower grade levels (OR = 1.12, p < 0.001), reduced monthly living costs (OR = 1.14, p = 0.014), lack of sexual experience (OR = 0.75, p = 0.015), and a higher degree of HIV/AIDS knowledge (OR = 1.617, p = 0.007) were positively correlated with supportive attitudes toward PLHIV.

CONCLUSION: Overall, the awareness rate of college students in Xuzhou City about HIV/AIDS infection awareness is high. However, only about half of the university students have positive attitudes toward PLHIV. In order to ensure that a thorough understanding of HIV/AIDS is matched by positive attitudes, it is important to implement targeted educational measures aimed at bridging the gap between knowledge and attitudes toward HIV/AIDS in order to develop a more informed and empathetic student body.

PMID:39450388 | PMC:PMC11500070 | DOI:10.3389/fpubh.2024.1398980

Front Public Health. 2024 Oct 10;12:1431001. doi: 10.3389/fpubh.2024.1431001. eCollection 2024.

ABSTRACT

BACKGROUND: Research on the correlation between exposure to per- and polyfluoroalkylated substances (PFASs)/heavy metals and bone health during childhood and adolescence is limited. Considering their role as endocrine disruptors, we examined relationships of six PFASs and three heavy metals with bone mineral density (BMD) in children and adolescents using representative samples from the National Health and Nutrition Examination Survey (NHANES).

METHODS: The study included 622 participants aged 12-19. The relationship between single pollutant and lumbar spine and total BMD was studied using linear regression analyses. Additionally, Bayesian Kernel Machine Regression (BKMR) models were applied to assess the joint effects of multiple PFASs and heavy metals exposure on the lumbar spine and total BMD.

RESULTS: Statistically significant differences were noted in the serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), blood lead (Pb), and blood manganese (Mn) between male and female participants (all p < 0.05). Single-exposure studies have shown that Mn was negatively correlated with lumbar spine BMD and total BMD. Multivariate linear regression models revealed that, in the male group, total bone density decreased as the blood PFOA levels [95% CI = (-0.031, -0.001), p = 0.040] and blood manganese levels [95% CI = (-0.009, -0.002), p = 0.004] increased. Similarly, lumbar spine bone density decreased as the blood manganese levels [95% CI = (-0.011, -0.002), p = 0.009] increased. In the female group, total bone density decreased as the serum PFNA levels [95% CI = (-0.039, 0.000), p = 0.048] increased. As shown in the BKMR model, the joint effects of pollutant mixtures, including Mn, were negatively associated with both the lumbar spine and total BMD. Among the pollutants analyzed, Mn appeared to be the primary contributor to this negative association.

CONCLUSION: This study suggests that exposure to certain PFASs and heavy metals may be associated with poor bone health. Childhood and adolescence are crucial stages for bone development, and improper exposure to PFASs and heavy metals during these stages could potentially jeopardize future bone health, consequently raising the risk of osteoporosis in adulthood.

PMID:39450387 | PMC:PMC11499139 | DOI:10.3389/fpubh.2024.1431001