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The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3-5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations., (© 2024 Wiley Periodicals LLC.)

Objective: Several studies have reported a high prevalence of hypovitaminosis D in orthopedic patients. The purpose of this prospective observational study was to report on the prevalence of hypovitaminosis D in patients scheduled for elective primary total knee arthroplasty (TKA) and its associated risk factors., Methods: In this monocentric cohort study, 25(OH) vitamin D serum levels were measured in 687 consecutive patients undergoing primary total knee arthroplasty (TKA) over a period of twelve months. Vitamin D levels were classified into deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), and sufficiency (≥30 ng/mL). The study assessed the association of vitamin D levels with demographic and clinical factors, including age, sex, BMI, smoking status, and season of measurement. Statistical analyses included chi-square tests, correlation analyses, and multiple linear regression to identify significant predictors of vitamin D levels., Results: The cohort had a mean age of 67.70 ± 8.95 years and a mean BMI of 31.00 ± 5.71 kg/m 2 . Collectively, 33.9% of patients were vitamin D deficient, a further 32.9% were insufficient, and only 33.2% were sufficient. Vitamin D levels varied significantly with the season and were associated with obesity and smoking. Specifically, there was a small significant inverse correlation between BMI and vitamin D levels (r = -0.17, p < 0.01). Furthermore, regular nicotine abuse was linked to lower vitamin D levels (r = 0.14, p < 0.01). Multiple linear regression analysis reveals that age, BMI, nicotine abuse, and season were small significant predictors of preoperative vitamin D levels (R 2 = 0.15, adjusted R 2 = 0.12). A total of 121 (17.61%) patients reported routine vitamin D intake prior to surgery. Supplementing patients had a significantly higher mean serum vitamin D level and a significant reduction in the mean length of in-hospital stay ( p < 0.01)., Conclusions: The prevalence of vitamin D insufficiency and deficiency in patients undergoing elective primary TKA is alarmingly high. In ongoing efforts to optimize the efficacy and outcome of the TKA procedure, orthopedic surgeons should be advised to strongly implement the role of perioperative vitamin D levels in their routine practice.

Introduction: The management of Peyronie's disease (PD) is a challenge for the clinician. Despite the lack of etiologic therapy, different nonsurgical approaches have often been empirically proposed. The most used treatment is based on nutraceutical drugs with antioxidant activity, although such an intervention remains controversial., Objectives: We reviewed the evidence from the randomized controlled trials included in the recommendations of the American Urological Association (AUA), Canadian Urological Association (CUA), European Association of Urology, and International Society for Sexual Medicine., Methods: We searched PubMed, Scopus, Web of Science, and Cochrane Library for randomized controlled trials, reviews, and guidelines on nutraceutical interventions for PD., Results: Our analysis provides detailed information on potential interventions, underlying the inconsistent evidence. Acetyl esters of carnitine, although not recommended by any of the available guidelines, showed potential benefit in some selected studies. Omega-3 fatty acids are not recommended due to withdrawn study evidence. The CUA and AUA were the only societies to consider the use of coenzyme Q10. While the CUA suggested that it might be offered as a treatment option, the AUA refrained from taking a definitive stance due to insufficient evidence. Similarly, conflicting recommendations have been produced on potassium para-aminobenzoate. While the CUA considers potassium para-aminobenzoate potentially useful in slowing PD progression, the AUA deems the evidence insufficient. Conversely, both the International Society for Sexual Medicine and European Association of Urology do not recommend its use., Conclusion: This critical comparative analysis of the most recent guidelines produced by the leading scientific societies highlights some inconsistencies in the recommendations on nutraceutical intervention for PD, even within a background of overall ineffectiveness of this treatment approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: Cognitive impairment is an intermediate state between normal aging and dementia, and its detection in the early stages is essential to prevent dementia, an incurable pathology. The aim of this study is to screen and estimate the prevalence of cognitive impairment, including dementia, and its correlated factors in a community-based sample of the Albanian population over 50 years old., Methods: We carried out a door-to-door neuropsychological screening of Albanian residents older than 50 years from November 2023 to June 2024 in 12 Albanian districts. Participants completed the Early Dementia Questionnaire (EDQ) and the Mini Mental State Examination (MMSE)., Results: The overall estimating prevalence of cognitive impairment and early dementia among the Albanian population over 50 years old was 14.04% using the MMSE, with 2.31% for MMSE ≤18 (serious cognitive impairment), 5.51% for MMSE 19-22 (mild cognitive impairment (MCI)), and 6.22 for MMSE 23-24 (suspected cognitive impairment or dementia),respectively. The prevalence of early dementia using the EDQ was significantly higher (53.99%).The number of male participants with MMSE scores of 23-24 (suspected cognitive impairment or early dementia) was 2.5 times higher with respect to female participants. Smoking and alcohol consumption decreased the MMSE scores. The number of participants with normal cognitive function (MMSE scores 25-30) was lower among participants with hypertension, diabetes, hyperlipidemia, and cerebral ischemia., Conclusions: A diagnostic evaluation, including a clinical examination, neuroimaging, and laboratory studies, is further required for a diagnosis. Despite limitations, the data provided in this study are the only ones reported for a large community-based sample of the older adult Albanian population, which can help health care providers to diagnose cognitive impairment.

Vitamin D is crucial for ideal bone health and good muscle function, both essential requirements for successful joint arthroplasty. Hence, vitamin D deficiency has recently been identified as a predictor of poorer outcomes in patients scheduled to undergo total joint arthroplasty (TJA). Moreover, there is ample evidence today that vitamin D deficiency is associated with periprosthetic joint infection. Yet, vitamin D deficiency seems to be frequent in patients who are scheduled to undergo TJA. However, the prevalence of hypovitaminosis D in patients who require revision arthroplasty (rTJA) is largely unknown. Further, risk factors of vitamin D deficiency in these patients remain to be elucidated. For this reason, the primary objective of this study was to assess the vitamin D status of patients scheduled to undergo rTJA of the hip, knee and shoulder. The secondary objective was to identify potential risk factors for hypovitaminosis D in these patients. Serum vitamin D [25(OH)D] levels of 249 patients who were scheduled for rTJA were assessed over a period of twelve months at a high-volume TJA centre. Collectively, 23% of patients reported a routine intake of vitamin D supplements (58/249). Notably, 81% of patients (155/191) who did not report a routine vitamin D intake presented with insufficient vitamin D levels (below 30 ng/mL), while only 19% of patients (36/191) had sufficient vitamin D levels. Of those who reported a routine vitamin D intake, 75% (43/58) had sufficient vitamin D levels, while 25% (15/58) showed insufficient vitamin D status. Patients who did not routinely take any vitamin D supplements had significantly lower vitamin D levels compared to patients who reported regular vitamin D intake (19.91 ng/mL vs. 40.66 ng/mL). Further, BMI and nicotine abuse were identified as potential risk factors for hypovitaminosis D in patients without vitamin D supplementation. Moreover, the season of spring seems to be a risk factor in patients with vitamin D supplementation, while age itself did not appear to be a significant risk factor for low vitamin D levels. In conclusion, we found an alarmingly high rate of vitamin D deficiency in patients scheduled to undergo rTJA. Notably, reported routine vitamin D supplementation showed significantly increased serum vitamin D levels compared to patients with no reported supplementation. Due to the high prevalence of vitamin D deficiency, we believe that vitamin D status should routinely be assessed in patients who are scheduled to undergo rTJA.

Objective: Starvation in early life can cause poor bone health and metabolic aberrations in bone minerals, leading to abnormal bone development. Holocaust survivors have been exposed to starvation and malnutrition before and during World War II. This paper aims to provide the current state of knowledge on the osteoporosis risk in Holocaust survivors and their descendants., Methods: The PubMed and Scopus databases were searched. Papers that reported original data on the risk of osteoporosis in Holocaust survivors and in their offspring were included in the study., Results: Ten studies were included in this review. The majority of studies were case-control ones (n=7) versus two self-reported and one longitudinal study. Despite the limited cohort numbers and the small number of studies in the literature, the data showed a potential increased risk of osteoporosis in Holocaust survivors and especially in their descendants., Conclusions: The review of these studies showed a higher prevalence of osteoporosis among Holocaust survivors and their offspring. Knowledge of the trans-generational inheritance of osteoporosis in the descendants of Holocaust survivors should increase the awareness of primary care health workers on osteoporosis screening and early diagnosis and implementation of preventive measures, including adequate vitamin D and calcium supplementation, and pharmacological treatment.

Background: Procedures on reporting adverse drug reactions (ADRs) in Albania are not yet standardised with the European Union despite continuous legislative changes. The aim of this study was to assess for the first time in Albania the reporting of ADRs by dentists and dental patients and to evaluate the frequency and timing of ADRs., Methods: We conducted a questionnaire-based survey for dentists and dental patients in Albania on their knowledge on ADR signalling. Dentists and their patients were randomly reached in private dental clinics. Ninety-five dentists and 640 dental patients from 5 different cities in Albania agreed to participate in the study. Only dentists who were actively working on their dental clinics and who volunteered to participate in the study were considered eligible., Results: The response rates were 95.0% and 91.4% for dentists and dental patients, respectively. In addition, 7.36% of dentists reported to have been informed on the national ADR signalling through conferences, but when asked about the procedures only 28.6% of them reported to have knowledge on the concrete process. None of the dental patients knew how to report ADRs., Conclusions: The findings demonstrate the complete lack of information on ADR signalling in a randomly selected group of 640 dental patients and 95 dentists surveyed. The results of the study are concerning and show that knowledge on ADR signalling should massively increase through public and social media., Competing Interests: Conflict of Interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to iron overload and multiorgan failure., Objectives: The aim of this systematic review was to provide up-to-date evidence of all the current data on the costs and cost effectiveness of screening and treatment for HH., Methods: We searched PubMed, Cochrane Library, National Health Service Economic Evaluation Database (NHSEED), Cost-Effectiveness Analysis Registry (CEA Registry), Health Technology Assessment Database (HTAD), Centre for Reviews and Dissemination (CRD), and Econlit until April 2023 with no date restrictions. Articles that reported cost-utility, cost-description, cost-minimization, cost-effectiveness, or cost-benefit analyses for any kind of management (drugs, screening, etc.) were included in the study. Patients with HH, their siblings, or individuals suspected of having HH were included in the study. All screening and treatment strategies were included. Two authors assessed the quality of evidence related to screening (either phenotype or genotype screening) and treatment (phlebotomy and electrophoresis). Narrative synthesis was used to analyse the similarities and differences between the respective studies., Results: Thirty-nine papers were included in this study. The majority of the studies reported both the cost of phenotype screening, including transferrin saturation (TS), serum ferritin, and liver biopsy, and the cost of genotype screening (HFE screening, C282Y mutation). Few studies reported the cost for phlebotomy and erythrocytapheresis treatment. Data revealed that either phenotype or genotype screening were cost effective compared with no screening. Treatment studies concluded that erythrocytapheresis might be a cost-effective therapy compared with phlebotomy., Conclusions: Economic studies on either the screening, or treatment strategy for HH patients should be performed in more countries. We suggest that cost-effectiveness studies on the role of deferasirox in HH should be carried out as an alternative therapy to phlebotomy., (© 2024. The Author(s).)

Background: The prevention of myelomeningocele (MMC) and meningocele (MC) is a public health concern. A systematic review on economic factors associated with MMC and MC can help the policy makers to evaluate the cost-effectiveness of screening and treatment. To our knowledge, this is the first systematic review to provide up-to date pharmacoeconomic evidence of all economic studies present in literature on different aspects of MMC and MC., Methods: We searched in the National Health Service Economic Evaluation Database (NHSEED), PubMed, Cost-effectiveness Analysis Registry (CEA Registry), Centre for Reviews and Dissemination (CRD), Health Technology Assessment Database (HTAD), Cochrane Library, and Econlit. The PRISMA guidelines were followed in the search and evaluation of literature. Only articles in English not limited by the year of publication that fulfilled the eligibility criteria were included in this systematic review., Results: Nineteen papers were included in the study. The studies were very heterogeneous and reported a comparison of the costs between prenatal versus postnatal repair, the cost of fetoscopic approach versus open surgery, the cost of ventriculoperitoneal shunting (VPS) versus endoscopic third ventriculostomy (ETV), and ETV with choroid plexus cauterization (ETV/CPC), the cost of hospitalization, and the cost of diagnosis for MMC., Conclusion: The results of this study can help in implementing new policies in different countries to assist MC and MMC patients with the cost of treatment and screening., Competing Interests: The authors declare that they have no competing interests for this work., (© 2024 Hoxha et al.)

Background : this study aims to investigate the accuracy and completeness of ChatGPT in answering questions and solving clinical scenarios of interceptive orthodontics. Materials and Methods : ten specialized orthodontists from ten Italian postgraduate orthodontics schools developed 21 clinical open-ended questions encompassing all of the subspecialities of interceptive orthodontics and 7 comprehensive clinical cases. Questions and scenarios were inputted into ChatGPT4, and the resulting answers were evaluated by the researchers using predefined accuracy (range 1-6) and completeness (range 1-3) Likert scales. Results : For the open-ended questions, the overall median score was 4.9/6 for the accuracy and 2.4/3 for completeness. In addition, the reviewers rated the accuracy of open-ended answers as entirely correct (score 6 on Likert scale) in 40.5% of cases and completeness as entirely correct (score 3 n Likert scale) in 50.5% of cases. As for the clinical cases, the overall median score was 4.9/6 for accuracy and 2.5/3 for completeness. Overall, the reviewers rated the accuracy of clinical case answers as entirely correct in 46% of cases and the completeness of clinical case answers as entirely correct in 54.3% of cases. Conclusions : The results showed a high level of accuracy and completeness in AI responses and a great ability to solve difficult clinical cases, but the answers were not 100% accurate and complete. ChatGPT is not yet sophisticated enough to replace the intellectual work of human beings.

Introduction: The two main psychological issues that people with end-stage renal disease (ESRD) experience are depression and anxiety. We conducted this study to determine both the prevalence of depression and anxiety, and the factors associated with them, among hemodialysis patients., Methods: Patients aged 18 years or older, who had received hemodialysis in a hemodialysis center in Elbasan, for at least 3 months were included in this study. Beck Anxiety Inventory and Beck Depression Inventory Instruments were used to assess hemodialysis patients levels of depression and anxiety., Results: Overall, 107 hemodialysis patients (men 65.4%) with a mean age of 57 ± 8.9 years were enrolled in the study. The prevalence of anxiety and depression resulted to be 85.98, and 84.11%, respectively. We found a significant difference in depression and anxiety scores in patients age groups of 61-70 years old (OR = 1.8; 95% CI [0.7-3.7]; p  = 0.041), in non-smoking patients (OR 3.4; 95% CI [1.09-8.2]; p  = 0.04), in diabetic patients (OR 3.4; 95% CI [1.09-8.2]; p  = 0.04), and in patients with a time in dialysis of 6-10 years and >11 years, respectively, (OR 3.4; 95% [1.5-9.0]; p  = 0.01), (OR1.3; 95% CI [0.4-3.6]; p  = 0.04)., Conclusion: Our study shows that the prevalence of mental disorders (depression and anxiety) is high among patients with ESRD on maintenance hemodialysis. We recommend a routine screening and referral to psychological health specialists to evaluate the mental health disorders among hemodialysis patients with the primary aim of improving their quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elezi, Abazaj, Zappacosta and Hoxha.)

Background: Thoracocentesis of pleural effusion is a simple technique for pleural fluid examination through cytology. In addition to cytological examination to assess the nature of pleural fluid content, we can also perform more detailed examinations through cytoblocks of residual fluid. These paraffin-embedded cytoblock samples are important because we can perform examinations as in other bioptic samples. In these samples, immunohistochemical and molecular analyses can be performed., Methods: Two hundred fifty-five cytological samples from patients with pleural effusion were examined. In cases in which the presence of malignant cells was identified in the cytological examination, as well as cases that were suspicious but not definitive for the presence of a malignant effusion, a cytoblock was prepared. Histological examination and immunohistochemical analysis were performed., Results: Among 255 cases with pleural effusion, 152 had the presence of malignant cells and 6 cases were suspicious, but uncertain for the presence of malignant cells, while 86 cases had inflammatory pleural effusion or other pathologies but were not malignant. After histological analysis of the cytoblock and immunohistochemical analysis, we identified 82 malignant tumors of the lung, 8 malignant tumors of the gastrointestinal tract, 15 malignant tumors of the breast, and 6 malignant tumors of the female genital tract, as well as 24 tumors of undetermined origin., Conclusions: Cytoblocks are important for the diagnosis of the primary nature of malignant pleural effusions. The highest importance is primary lung tumors, as well as those tumors in which the primary site of the tumor cannot be determined clinically., (© 2023 Wiley Periodicals LLC.)

Purpose: This investigation describes the outcomes of pediatric ganglion cysts in a prospective cohort that elected not to undergo cyst aspiration or surgical treatment. Our primary aim was to investigate the rate of spontaneous resolution over time among the subset of patients who did not undergo specific treatments., Methods: Children (aged ≤18 years) who presented to the clinic with ganglion cysts of the hand or wrist were enrolled in a prospective two-center registry between 2017 and 2021. Enrolled subjects who never elected to undergo cyst aspiration or surgical treatment were analyzed. The data collected included age, sex, cyst location and laterality, hand dominance, Wong-Baker pain scale scores, and Patient-Reported Outcome Measurement Information System upper-extremity scores. Follow-up surveys were completed for up to 5 years., Results: A total of 157 cysts in 154 children, with an average age of 9.4 years and a female-to-male ratio of 1.4:1, were eligible. The most common ganglion location was dorsal wrist (67/157, 42.7%), followed by volar wrist (49/157, 31.2%), the flexor tendon sheath (29/157, 18.5%), and the extensor tendon synovial lining (8/157, 5.1%). The average follow-up duration was 2.5 years after initial presentation to the clinic, and 63.1% (99/157) of the patients responded to follow-up surveys. Among them, 62.6% (62/99) of cysts spontaneously resolved; the resolution rates ranged from 51.9% of volar wrist ganglions to 81% of flexor tendon sheath cysts, with an average time to resolution of 14.1 months after cyst presentation. Cysts were more likely to resolve in the hand than in the wrist (84.0% vs 55.4%, respectively). Cysts present for >12 months at initial evaluation were less likely to resolve spontaneously (41.2% vs 67.1%)., Conclusions: Of children who elected not to undergo aspiration or surgical treatment, approximately two-thirds of families reported that their child's ganglion cyst resolved spontaneously. Cysts that resolve spontaneously usually do so within 2 years of presentation., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023. Published by Elsevier Inc.)

Meteoropathy is no longer considered a popular myth, but a new disease that significantly impacts daily life, particularly in individuals who experience mental illness, cardiovascular disorders, and respiratory conditions. However, there are very limited data on this condition. This study aimed to comprehensively review and analyze existing in vivo animal studies and human clinical trials investigating the effects of meteoropathy on health and its pharmacological treatment. A thorough literature search was conducted across databases such as PubMed and Scopus to gather relevant information. Our analysis primarily focused on the relationship between meteoropathy and mental health, including the influence on affective temperaments. Additionally, we explored various treatment approaches, emphasizing the combination of muscle exercises, pharmacological interventions, and naturopathy, which have shown promise in alleviating pain among individuals affected by meteoropathy. Future research in meteoropathy should shed light on synthesizing new pharmacological compounds., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Human endogenous retroviruses (HERVs) are transposable genomic elements generally repressed through DNA methylation. HERVs can be demethylated and expressed in response to environmental stimuli. Therefore, more research is needed to understand the influence of environmental exposures on HERV methylation. Air pollutants are commonly linked with global hypomethylation, and as HERVs comprise of nearly 8% of repetitive elements in the human genome, our objective was to examine the association between air pollutant exposure and HERV methylation. We investigated 180 students with asthma participating in the School Inner-City Asthma Intervention Study, which evaluated the efficacy of classroom air filters and school-wide pest management on air pollutant/allergen exposure and asthma. Both air pollutants measured in classrooms and asthma outcomes assessed by surveys were collected pre- and post-intervention. Buccal swabs were also collected pre- and post-intervention, and methylation levels from 9 transposable genomic elements (HERV-E, -FRD, -K, -L, -R, -W, -9, and HRES and LINE1) were measured. Adjusting for relevant covariates, the overall air pollutant mixture was cross-sectionally associated with higher HERV-W and lower HERV-L and LINE1 methylation. Coarse PM was cross-sectionally associated with higher HERV-K methylation and CO2 with lower LINE1 methylation. These results suggest that exposure to air pollutants is associated with HERV-W and HERV-K hypermethylation and HERV-L and LINE1 hypomethylation in children with asthma. Future studies are needed to characterize the links between HERV methylation and possible adverse outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE 1 and PGE 2 ), PGF 2α , and their specific 19-hydroxy derivatives, 18,19-dehydro derivatives of PGE 1 and PGE 2 . The objective of this study is to synthesize the available literature of in vivo animal studies and human clinical trials on the association between the AA pathway and male fertility. PGE is significantly decreased in the semen of infertile men, suggesting the potential for exploitation of PGE agonists to improve male fertility. Indeed, ibuprofen can affect male fertility by promoting alterations in sperm function and standard semen parameters. The results showed that targeting the AA pathways could be an attractive strategy for the treatment of male fertility.

Background: Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn)., Methods: The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup&#95;PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ&#95;PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA&#95;changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships., Results: In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA&#95;changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup&#95;PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA&#95;changes (p < 0.0001) which is in turn triggered by Occup&#95;PAHs and Environ&#95;PAHs., Conclusions: Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented., (© 2023. The Author(s).)

Colorectal cancer (CRC) is the third leading cause of mortality in cancer patients. The role of fatty acids (FA) and their metabolism in cancer, particularly in CRC raises a growing interest. In particular, dysregulation of synthesis, desaturation, elongation, and mitochondrial oxidation of fatty acids are involved. Here we review the current evidence on the link between cancer, in particular CRC, and fatty acids metabolism, not only to provide insight on its pathogenesis, but also on the development of novel biomarkers and innovative pharmacological therapies that are based on FAs dependency of cancer cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoxha and Zappacosta.)

The impact of exposure to respirable particulate matter (PM) during pregnancy is a growing concern, as several studies have associated increased risks of adverse pregnancy and birth outcomes, and impaired intrauterine growth with air pollution. The molecular mechanisms responsible for such effects are still under debate. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues (e.g., pulmonary environment and placenta), might play an important role in PM-induced risk. We sought to determine whether the levels of PM with aerodynamic diameters of ≤10 µm (PM 10 ) and ≤2.5 µm (PM 2.5 ) are associated with changes in plasmatic EV release and EV-miRNA content by investigating 518 women enrolled in the INSIDE study during the first trimester of pregnancy. In all models, we included both the 90-day averages of PM (long-term effects) and the differences between the daily estimate of PM and the 90-day average (short-term effects). Short-term PM 10 and PM 2.5 were associated with increased concentrations of all seven EV types that we assayed (positive for human antigen leukocyte G (HLA-G), Syncytin-1 (Sync-1), CD14, CD105, CD62e, CD61, or CD25 determinants), while long-term PM 10 showed a trend towards decreased EV concentrations. Increased Sync-1 + EV levels were associated with the plasmatic decrease of sVCAM-1, but not of sICAM-1, which are circulating biomarkers of endothelial dysfunction. Thirteen EV-miRNAs were downregulated in response to long-term PM 10 and PM 2.5 variations, while seven were upregulated (p-value < 0.05, false discovery rate p-value (qFDR) < 0.1). Only one EV-miRNA (hsa-miR-221-3p) was downregulated after short-term variations. The identified PM-modulated EV-miRNAs exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia, as highlighted by miRNA target analysis. Our findings strongly support the hypothesis that EVs have an important role in modulating PM exposure effects during pregnancy, possibly through their miRNA cargo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance is a threat to global public health. The use of prolonged infusions in the hospital setting for certain antimicrobials is widely increasing in order to improve their efficacy and safety, including resistance development. Due to limited vascular access, it is important to clarify whether they can be infused through the same line with other drugs during Y-site administration., Aim: The aim of this review is to update and summarize the evidence on Y-site compatibility of antibacterial agents administered as prolonged infusions in intensive care units (ICUs)., Study Design: A literature review of PubMed, EMBASE and Trissel's Handbook on Injectable Drugs databases was conducted on the compatibility of selected antimicrobials administered simultaneously at a Y-site connection with parenteral nutrition and other widely used drugs in ICUs. All articles published up to October 30, 2021, in English or Spanish were included, regardless of the type of publication (original articles, case reports, letters, etc.). Eligible antimicrobials were those that can be administered as prolonged infusions: ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ceftolozane/tazobactam, ceftaroline, cloxacillin, ceftobiprole, vancomycin and fosfomycin., Results: A total of 1302 drug-to-drug potential combinations were explored, 196 (15.05%) were found to be incompatible, and in 541 (41.55%), data were not available. The results were presented in a simple 2-dimensional consultation chart as a quick reference for health care professionals., Conclusions: This review provides useful and reliable information on the compatibility of antimicrobials administered as Y-site infusion with other drugs commonly used in the critical setting. This review contributes to patient safety in nursing practice., Relevance to Clinical Practice: To our knowledge, this is the first review on Y-site compatibility of antimicrobials used as prolonged infusions with other commonly used drugs, including anti-emetics, analgesics and anti-epileptic and parenteral nutrition. The results of the current review need to be addressed to promote the knowledge sharing between health professionals and improve the quality and safety of patients. We believe that this review may serve as a simple and effective 2-dimensional updated drug-to-drug compatibility reference chart for critical care nurses., (© 2022 British Association of Critical Care Nurses.)

The possibility of characterizing the extracellular vesicles (EVs) based on parental cell surface markers and their content makes them a new attractive prognostic biomarker. Thus, our study aims to verify the role of EVs as relevant prognostic factors for acute and mid-term outcomes in ischemic stroke. Forty-seven patients with acute ischemic stroke were evaluated at admission (T0), immediately after recanalization treatment or after 2 h in non-treated patients (T1) and after one week (Tw) using the National Institutes of Health Stroke Scale (NIHSS), and after 3 months using the Modified Rankin Scale (mRS). Total count and characterization of EVs were assessed by Nanosight analysis and flow cytometry. The relationships between stroke outcomes and EV count were assessed through multivariable negative binomial regression models. We found that the amount of platelet-derived EVs at admission was positively associated with the severity of ischemic stroke at the onset as well as with the severity of mid-term outcome. Moreover, our study revealed that T-cell-derived EVs at admission were positively related to both early and mid-term ischemic stroke outcomes. Finally, T-cell-derived EVs at T1 were positively related to mid-term ischemic stroke outcome. The present study suggests that specific EV subtypes are associated with stroke severity and both short- and long-term outcomes. EVs could represent a valid tool to improve risk stratification in patients with ischemic stroke and post-recanalization treatment monitoring.

Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient's immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy.

Objective: To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate., Design: Prospective cohort study., Setting: Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico., Patients: 181 women aged 37-39 years who underwent IVF at a single-centre between January 2017 and December 2018., Interventions: On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation., Main Outcome Measures: This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles., Results: TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 ± 4.2 and 37.3 ± 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82-0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82-0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83-1.00, p = 0.048)., Conclusion: DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Somigliana reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, personal fees from Gedeon-Richter, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials, as detailed online in your guide for authors. All the other authors have no competing interests in relation to this study.

Background: Extracellular vesicles (EV) concentration is generally increased in patients with cardiovascular diseases, although the protective role of EVs in atherosclerosis has been reported. Among the specific cargo of EVs, miRNAs contribute to different stages of atherosclerosis. Aim of the present report has been to investigate, in individuals with obesity, the interplay among EVs derived from cells relevant for the atherosclerotic process (i.e., platelets, endothelium, monocytes/macrophages, and neutrophils), their miRNA content and proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the main regulators of low-density lipoprotein receptor (LDLR). Methods and Results: EVs have been isolated from 936 individuals with obesity (body mass index = 33.6 ± 5.6 Kg/m 2 ) and a raised cardiovascular risk (e.g., LDL-C = 131.6 ± 36.4 mg/dL, HOMA-IR = 3.1, and roughly 50% on anti-hypertensive medications). PCSK9 levels were negatively associated with EV count in the range 150-400 nm and with those derived from macrophages (CD14 + ), endothelium (CD105 + ), and neutrophils (CD66 + ). The association between PCSK9 and platelet-derived EVs (CD61 + ) was modified by platelet counts. PCSK9 was significantly associated with five EV-derived miRNAs (hsa-miRNA-362-5p,-150,-1244,-520b-3p,-638). Toll-like receptor 4 and estrogen receptor 1 were targeted by all five miRNAs and LDLR by four. The effect on LDLR expression is mainly driven by hsa-miR-150. Considering the implication of EV in atherosclerosis onset and progression, our findings show a potential role of PCSK9 to regulate EV-derived miRNAs, especially those involved in inflammation and expression of low-density lipoprotein receptor (LDLR) receptor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PM declared a shared affiliation, with one of the authors LV to the handling editor at the time of the review., (Copyright © 2022 Macchi, Greco, Favero, Dioni, Cantone, Hoxha, Vigna, Solazzo, Corsini, Banach, Pesatori, Bollati and Ruscica.)

Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors (SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.2) likewise expressed in the pre-post synapsis of neurons and inflammatory cells, thereby affecting their proliferation and activity. KATP channels are involved in amyloid-β (Aβ)-induced pathology, therefore emerging as therapeutic targets against Alzheimer's and related diseases. The modulation of these channels can represent an innovative strategy for the treatment of neurodegenerative disorders; nevertheless, the currently available drugs are not selective for brain KATP channels and show contrasting effects. This phenomenon can be a consequence of the multiple physiological roles of the different varieties of KATP channels. Openings of cardiac and muscular KATP channel subunits, are protective against caspase-dependent atrophy in these tissues and some neurodegenerative disorders, whereas in some neuroinflammatory diseases, benefits can be obtained through the inhibition of neuronal KATP channel subunits. For example, glibenclamide exerts an anti-inflammatory effect in respiratory, digestive, urological, and central nervous system (CNS) diseases, as well as in ischemia-reperfusion injury associated with abnormal SUR1-Trpm4/TNF-α or SUR1-Trpm4/ Nos2/ROS signaling. Despite this strategy being promising, glibenclamide may have limited clinical efficacy due to its unselective blocking action of SUR2A/B subunits also expressed in cardiovascular apparatus with pro-arrhythmic effects and SUR1 expressed in pancreatic beta cells with hypoglycemic risk. Alternatively, neuronal selective dual modulators showing agonist/antagonist actions on KATP channels can be an option., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by destruction of oligodendrocytes, immune cell infiltration and demyelination. Inflammation plays a significant role in MS, and the inflammatory mediators such as eicosanoids, leukotrienes, and superoxide radicals are involved in pro-inflammatory responses in MS. In this systematic review, we tried to define and discuss all the findings of in vivo animal studies and human clinical trials on the potential association between arachidonic acid (AA) pathway and multiple sclerosis., Methods: A systematic literature search across Pubmed, Scopus, Embase and Cochrane database was conducted. This systematic review was performed according to PRISMA guidelines., Results: A total of 146 studies were included, of which 34 were conducted on animals, 58 on humans, and 60 studies reported the role of different compounds that target AA mediators or their corresponding enzymes/receptors, and can have a therapeutic effect in MS. These results suggest that eicosanoids have significant roles in Experimental Autoimmune Encephalomyelitis (EAE) and MS. The data from animal and human studies elucidated that PGI 2 , PGFI 2α , PGDI 2 , isoprostanes, PGEI 2 , PLAI 2 , and LTs are increased in MS. PLAI 2 inhibition modulates the progression of the disease. PGE1 analogues can be a useful option in the treatment of MS., Conclusion: All studies reported the beneficial effects of COX and LOX inhibitors in MS. The hybrid compounds, such as COX-2 inhibitors/TP antagonists and 5-LOX inhibitors, can be an innovative approach for multiple sclerosis treatment. Future work in MS should shed light on synthesizing new compounds targeting the arachidonic acid pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Reduced telomere length (TL) has been associated with increased risk of age-related diseases, most likely through oxidative stress and inflammation, which have also been claimed as mechanisms underlying health effects of air pollution exposure. We aimed to verify whether exposure to particulate matter with diameter ≤10 µm (PM 10 ) affects TL. We recruited 1792 participants with overweight/obesity in Milan (Italy) in 2010-2015 who completed a structured questionnaire on sociodemographic data, gave a blood sample for TL measurement by real-time PCR, and were assigned air pollution and meteorological data of their residential address. In multivariate mixed-effects linear models (with a random intercept on PCR plate), we observed a -0.51% change in TL (95% confidence interval (CI): -0.98; -0.05)) per 10 µg/m 3 increase in PM 10 at the day of recruitment. A similar decreasing trend in TL was observed up to two weeks before withdrawal, with percentage changes as low as -1.53% (average exposure of the 12 days before recruitment). Mean annual exposure to PM 10 was associated with -2.57% TL reduction (95%CI: -5.06; -0.08). By showing consistent associations between short- and long-term PM 10 exposures and reduced TL, our findings shed light on the potential mechanisms responsible for the excess of age-related diseases associated with air pollution exposure.

Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in improving childhood behavioral outcomes and underline its role as a modifiable risk factor for autism spectrum disorders. The aim of this systematic review is to both elucidate the potential role of folic acid in autism spectrum disorders and to investigate the mechanisms involved. Studies have pointed out a potential beneficial effect of prenatal folic acid maternal supplementation (600 µg) on the risk of autism spectrum disorder onset, but opposite results have been reported as well. Folic acid and/or folinic acid supplementation in autism spectrum disorder diagnosed children has led to improvements, both in some neurologic and behavioral symptoms and in the concentration of one-carbon metabolites. Several authors report an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children. Furthermore, methylene tetrahydrofolate reductase (MTHFR) polymorphisms showed a significant influence on ASD risk. More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.

Infants with congenital diaphragmatic hernia (CDH) are at high risk of postnatal mortality due to lung hypoplasia and arterial pulmonary hypertension. In severe cases, prenatal intervention by fetal endoscopic tracheal occlusion (FETO) can improve survival by accelerating lung growth. However, postnatal mortality remains in the range of about 50% despite fetal treatment, and there is currently no clear explanation for this different clinical response to FETO. We evaluated the concentration of extracellular vesicles (EVs) and associated microRNA expression in amniotic and tracheal fluids of fetuses with CDH undergoing FETO, and we examined the association between molecular findings and postnatal survival. We observed a higher count of EVs in the amniotic fluid of non-survivors and in the tracheal fluid sampled in utero at the time of reversal of tracheal occlusion, suggesting a pro-inflammatory lung reactivity that is already established in utero and that could be associated with a worse postnatal clinical course. In addition, we observed differential regulation of four EV-enclosed miRNAs (miR-379-5p, miR-889-3p; miR-223-3p; miR-503-5p) in relation to postnatal survival, with target genes possibly involved in altered lung development. Future research should investigate molecular therapeutic agents targeting differentially regulated miRNAs to normalize their expression and potentially improve clinical outcomes.

Duchenne muscular dystrophy (DMD) is a muscular disease characterized by progressive muscle degeneration. Life expectancy is between 30 and 50 years, and death is correlated with cardiac or respiratory complications. Currently, there is no cure, so there is a great interest in new pharmacological targets. Sirtuin1 (SIRT1) seems to be a potential target for DMD. In muscle tissue, SIRT1 exerts anti-inflammatory and antioxidant effects. The aim of this study is to summarize all the findings of in vivo and in vitro literature studies about the potential role of SIRT1 in DMD. A systematic literature search was performed according to PRISMA guidelines. Twenty-three articles satisfied the eligibility criteria. It emerged that SIRT1 inhibition led to muscle fragility, while conversely its activation improved muscle function. Additionally, resveratrol, a SIRT1 activator, has brought beneficial effects to the skeletal, cardiac and respiratory muscles by exerting anti-inflammatory activity that leads to reduced myofiber wasting.

Objectives: In Italy, the pandemic of COVID-19 resulted in congestion of hospitals and laboratories and probably determined an underestimation of the number of infected subjects, as the molecular diagnosis of SARS-CoV-2 infection was mainly performed on hospitalised patients. Therefore, limited data are available about the number of asymptomatic/paucisymptomatic subjects in the general population across time. To understand SARS-CoV-2 infection in the general population, we have developed a cross-sectional study (the 'UNIversity against CORoNavirus study') to investigate infection trends in asymptomatic/paucisymptomatic subjects in Milan (Italy), between March and June 2020., Participants: The study population included 2023 subjects asymptomatic at the enrolment., Primary Outcome Measures: A nasal mid-turbinate swab for the detection of SARS-CoV-2 RNA and blood specimen for testing serum antibodies (immunoglobulin M (IgM) and IgG) were collected., Results: Subjects showing positivity for the SARS-CoV-2 RNA and/or for anti-SARS-CoV-2 Ig is 237 (11.7%). Only 1.2% (n=25) of the total population had a positive nasal swab for SARS-CoV-2 and the large majority (21/25) of them were observed in March. A total of 226 subjects (11%) had IgM (n=19; 0.9%), IgG (n=155; 7.7%) or both (n=52; 2.6%) against SARS-CoV-2. Subjects with a present or past SARS-CoV-2 infection did not differ from other subjects as regards the number of cohabiting family members, travels, fever and upper and lower respiratory infection episodes., Conclusions: Results from the present study support the hypothesis that the actual spread of the virus in Lombardy was underestimated in the official records. However, as it is not known how long Ig persist, numbers should be taken cautiously., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on eight hundred adult asthmatic patients 18 years or older in Albania, equally distributed into two cohorts, exposed or nonexposed to montelukast usage, matched by age and gender according to information reported in the data collection. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. In summary, 37 (4.6%) of the asthmatic patients, 32 nonexposed, and five exposed to montelukast suffered a major cardiovascular event during the 3-year observation period. All the cardiovascular events, in either group, occurred among patients with an increased cardiovascular risk. Our analyses demonstrate that, independent from gender, exposure to montelukast remained a significant protective factor for incident ischemic events (78% or 76% risk reduction depending on type of analysis). The event-free Kaplan-Meier survival curves confirmed the lower cardiovascular event incidence in patients exposed to montelukast. Our data suggest that there is a potential preventative role of montelukast for incident cardiac ischemic events in the older asthmatic population, indicating a comorbidity benefit of montelukast usage in asthmatics by targeting cysteinyl leukotriene-driven cardiac disease inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a shared affiliation, though no other collaboration, with one of the authors JE., (Copyright © 2021 Hoxha, Tedesco, Quaglini, Malaj, Pustina, Capra, Evans, Sala and Rovati.)

Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases, including cardiovascular disease (CVD), inflammation, neurological diseases, cancer, and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation, as shown by the development of CVD, following the imbalance of its metabolites. This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. In silico literature searches were performed on PubMed and Scopus as main sources. Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI2), thromboxane (TXA), epoxyeicosatrienoic acids (EETs), and hydroxyeicosatetraenoic acids (HETEs). It is believed that by targeting Hcy in the AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for a dietician to manipulate diets to improve health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)