Search

Malaria-elimination interventions aim to extinguish hotspots and prevent transmission to nearby areas. Here, we re-analyzed a cluster-randomized trial of reactive, focal interventions (chemoprevention using artemether-lumefantrine and/or indoor residual spraying with pirimiphos-methyl) delivered within 500 m of confirmed malaria index cases in Namibia to measure direct effects (among intervention recipients within 500 m) and spillover effects (among non-intervention recipients within 3 km) on incidence, prevalence and seroprevalence. There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power. There was the strongest evidence of spillover effects of combined chemoprevention and indoor residual spraying. Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20-59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6-95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20-45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%. Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemotherapy and protect against chemotherapy-induced toxicity due to its scavenging properties. Furthermore, chemical compounds in cardamom, including limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, and diindolylmethane, primarily target the programmed cell death lignin-1 gene, which is more prevalent in cancer cells than in healthy cells. This review provides the medicinal properties and pharmacological uses of cardamom, its cellular effects, and potential therapeutic uses in cancer prevention and treatment, as well as its use in reducing drug resistance and improving the overall health of cancer patients. Based on previous preclinical studies, cardamom shows significant potential as an anti-cancer agent, but further exploration for clinical use is warranted due to its diverse mechanisms of action.

BACKGROUND: Early initiation of venous thromboembolism (VTE) chemoprophylaxis in adults with blunt solid organ injury (BSOI) has been demonstrated to be safe but this is controversial in adolescents. We hypothesized that adolescent patients with BSOI undergoing non-operative management (NOM) and receiving early VTE chemoprophylaxis (eVTEP) (≤ 48 h) have a decreased rate of VTE and similar rate of failure of NOM, compared to similarly matched adolescents receiving delayed VTE chemoprophylaxis (dVTEP) (> 48 h). METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for adolescents (12-17 years of age) with BSOI (liver, kidney, and/or spleen) undergoing NOM. We compared eVTEP versus dVTEP using a 1:1 propensity score model, matching for age, comorbidities, BSOI grade, injury severity score, hypotension on arrival, and need for transfusions. We performed subset analyses in patients with isolated spleen, kidney, and liver injury. RESULTS: From 1022 cases, 417 (40.8%) adolescents received eVTEP. After matching, there was no difference in matched variables (all p > 0.05). Both groups had a similar rate of VTE (dVTEP 0.6% vs. eVTEP 1.7%, p = 0.16), mortality (dVTEP 0.3% vs. eVTEP 0%, p = 0.32), and failure of NOM (eVTEP 6.7% vs. dVTEP 7.3%, p = 0.77). These findings remained true in all subset analyses of isolated solid organ injury (all p > 0.05). CONCLUSIONS: The rate of VTE with adolescent BSOI is exceedingly rare. Early VTE chemoprophylaxis in adolescent BSOI does not increase the rate of failing NOM. However, unlike adult trauma patients, adolescent patients with BSOI receiving eVTEP had a similar rate of VTE and death, compared to adolescents receiving dVTEP.

ImportanceRepeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions.ObjectiveTo evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.Design, setting, and participantsThis cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities.InterventionsCommunities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023.Main outcomes and measuresThe primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.ResultsA total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months.Conclusions and relevanceMortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.Trial registrationClinicalTrials.gov Identifier: NCT03676764.

The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.

AbstractHydroxyurea (HU) exerts unique and diverse biological effects as an anti-leukemic agent, irradiation sensitizer, and HbS inducer in patients with sickle cell anemia. Herein, we assessed the potential toxicogenic and/or oxidant effects of hydroxyurea associated with ascorbic acid by in vivo examinations in Allium cepa and human cancer cells and systemically on mice tissues. Growing A. cepa roots and HCT-116 colorectal tumor cells were examined after HU and HU plus ascorbic acid exposure. DNA damage and antioxidant enzymatic activity were quantified in peripheral blood mononuclear cells (PBMC), bone marrow leukocytes and livers of mice after 7 day-HU treatment (7.5, 15 and 30 mg/kg/day) and Vitamin C 2 μM. Hydroxyurea presented toxic effects on meristematic Allium cepa cells, causing chromosomal abnormalities and reduction of mitotic index, killed HCT-116 colorectal carcinoma cells and induced DNA injuries upon mice cells (hepatocytes, bone marrow leukocytes and PBMC). Simultaneously, hydroxyurea decreased levels of CAT and GSH activities and expand lipid peroxidation. All these biochemical and physiological changes were ameliorated when associated with ascorbic acid, indicating it restored antioxidant enzymes, decreased MDA levels, removed peroxides and, consequently, presented cytoprotection against HU-provoked cellular damage in normal cells. On the other hand, antioxidants compounds may interfere on effectiveness of HU during anticancer chemotherapies. [ABSTRACT FROM AUTHOR]

Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012–2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (I51R59N108 - G437) was the most common (72.6%), and the fully resistant haplotype (I51R59N108 - G437E540) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype I51R59N108 - V431A436G437G581S613 deserve more attention. In areas of high SP resistance, the intervention still reduces low birthweight and maternal anaemia. SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi). [ABSTRACT FROM AUTHOR]

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies. Our study aimed to investigate the influence of common medication intake and modifiable risk factors on FE gene expression using a colonic mucosa sample dataset of healthy individuals (BarcUVa-Seq). We applied expression enrichment analysis of the FE genes for each studied medication and factor. Both observational and instrumental (Mendelian randomization) analysis were conducted, and the results were validated using independent datasets. The findings from the observational and instrumental analyses consistently showed that medication intake, especially metformin, considerably downregulated the FE genes. Chemopreventive effects were also noted for antihypertensive drugs targeting the renin–angiotensin system. Conversely, benzodiazepines usage might upregulate FE genes, thus fostering a tumor-promoting microenvironment. In contrast, the findings from the observational and instrumental analyses on modifiable risk factors showed some discrepancies. The instrumental results indicated that obesity and smoking might promote a tumor-favorable microenvironment. These findings offer insights into the biological mechanisms through which risk factors might influence CRC development and highlight the potential chemopreventive roles of metformin and antihypertensive drugs in CRC risk. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To understand how lower limb immobilisation creates a risk of deep vein thrombosis and the individual risk factors that can compound this risk • To familiarise yourself with the methods of pharmacological thromboprophylaxis that may be used • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein, causing disruption or complete occlusion of blood flow. People who require lower limb immobilisation – for example after an injury such as metatarsal fracture, Achilles tendon rupture or malleolar fracture – are at increased risk of DVT, since epithelial injury and stasis will be present. Various patient-related and admission-related risk factors can further increase the risk of DVT. It is crucial that patients are individually assessed to determine their risk of DVT and their need for pharmacological thromboprophylaxis. This article discusses the indications for lower limb immobilisation, the mechanisms by which lower limb immobilisation creates a risk of DVT and the individual risk factors that compound the risk of thrombosis. It also outlines the importance of individualised risk assessments, the methods of pharmacological thromboprophylaxis and the nurse’s role in providing patient education. [ABSTRACT FROM AUTHOR]

Caffeic acid is a common phenolic acid found in coffee and numerous fruits and vegetables. Known for its antioxidant properties, it is widely used as a dietary supplement as part of a polyphenol mixture or as an extract in the form of a capsule or powder. It is also available in liquid form as a homeopathic supplement. Caffeic acid phenethyl ester (CAPE) is an active component of propolis produced by honey bees. Propolis extract is used as a supplement and is available in various forms. The present paper is a comprehensive review of the biomedical literature, showing that caffeic acid effects are hormetic and occur in numerous biological models and cell types for a broad range of endpoints including many aging-related processes. Hormesis is a biphasic dose/concentration response displaying a low concentration/dose stimulation and a high concentration/dose inhibition. Complex alternative search strategies for caffeic acid were used since publications rarely used the terms hormesis or hormetic. Evaluation of the data provides the first assessment of caffeic acid-induced hormetic concentration/dose responses and their quantitative features. Their mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications are discussed. Suggestions for future research are presented. [ABSTRACT FROM AUTHOR]

Objective We evaluated if venous thromboembolism (VTE) prophylaxis in the inpatient antepartum period was associated with wound hematomas, VTE occurrence, and other adverse outcomes. Study Design This study is a secondary analysis of a retrospective cohort of patients who delivered at University of Alabama at Birmingham (UAB). Patients receiving outpatient anticoagulation (AC) were excluded. We grouped patients into those who received inpatient antepartum prophylactic AC and those who did not. The primary outcome was wound hematomas from delivery to 6 weeks postpartum (PP). Secondary outcomes included VTE occurrence and select adverse outcomes, including other wound complications, unplanned procedures, mode of anesthesia, and intensive care unit (ICU) admission. Analyses were performed with no AC group as the reference. A sensitivity analysis excluding those who received inpatient PP AC was performed. Results Of 1,035 included patients, only 169 patients received inpatient prophylactic AC. They were older, had higher body mass indices, and more comorbidities. Patients receiving inpatient antepartum AC had higher wound hematomas (adjusted odds ratio [aOR] 23.81; 95% confidence interval [CI] 7.04–80.47). They had similar risk for developing VTE as the control group (aOR 2.68; 95% CI 0.19–37.49) but were more likely to have wound complications (aOR 2.36; 95% CI 1.24–4.47), maternal deaths (p < 0.05), and require PP ICU admission (aOR 13.38; 95% CI 4.79–37.35). When excluding those receiving any PP AC, there was no difference in bleeding complications between the two groups and VTE rates remained unchanged. Rates of maternal deaths and PP ICU admissions remained higher in those who received inpatient antepartum AC prophylaxis. Conclusion In this small cohort study, increased wound hematomas were found in those who received inpatient antepartum AC prophylaxis with no difference in VTE occurrence. While adverse events were increased in the inpatient AC group, this was mostly associated with PP AC prophylaxis. Larger studies should be conducted to describe the true benefits and risks of antepartum AC prophylaxis and determine efficacy of this widely used practice. Key Points Peripartum chemoprophylaxis is associated with increased wound hematomas. VTE is rare, despite its association with significant peripartum morbidity/mortality. Large studies are needed to guide practices that optimize the risk/benefit ratio of chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Broccoli (Brassica oleracea var. italica) is one of the most consumed cruciferous crops in the world, with China and Spain acting as the main producers from outside and within the EU, respectively. Broccoli florets are edible, while the leaves and stalks, discarded in the field and during processing, are by-products. Therefore, the objective of this study was to conduct a comprehensive review of the nutrient and phytochemical composition of broccoli and its by-products, as well as its beneficial effects. In addition, the study highlights the revalorization of broccoli by-products through innovative green technologies and explores their potential use in bakery products for the development of functional foods. The studies suggested that broccoli is characterized by a high content of nutrients and bioactive compounds, including vitamins, fiber, glucosinolates, and phenolic compounds, and their content varied with various parts. This high content of value-added compounds gives broccoli and its various parts beneficial properties, including anti-cancer, anti-inflammatory, antioxidant, antimicrobial, metabolic disorder regulatory, and neuroprotective effects. Furthermore, broccoli and its by-products can play a key role in food applications by improving the nutritional profile of products due to their rich content of bioactive compounds. As a result, it is essential to harness the potential of the broccoli and its by-products that are generated during its processing through an appropriate agro-industrial revalorization, using environmentally friendly techniques. [ABSTRACT FROM AUTHOR]

Common digestive precancerous lesions, including oral potentially malignant disorders (OPMDs), gastric ulcers and colorectal adenoma, harbor high risk of cancerous transformation. Early intervention of these lesions is significant to prevent carcinogenesis and improve patients’ prognosis. Lycopene, a carotenoid predominantly accumulated in tomatoes, is clinically recommended with its cis structure; as lycopene harbors the most potent antioxidative effects among carotenoids, its chemopreventive effects on the premalignant lesions is noted. Despite several reviews have assessed lycopene’s efficacy for OPMDs, emerging studies have reported varying efficacy for digestive precancerous lesion with no comprehensive summary. Therefore, this review initially evaluates the efficacy and underlying mechanisms of lycopene for management of digestive precancerous lesions. According to the included studies, lycopene may show high promise in the management of digestive precancerous lesions, such as relieving mouth opening and burning sensation of oral submucous fibrosis (OSF), presenting potentially equivalent efficacy on managing oral lichen planus (OLP) as steroids and alleviating gastrointestinal precancers’ symptoms, meanwhile lowering colon cancer risk. Moreover, its mechanisms for managing digestive precancerous lesions are concretely summarized, including anti-oxidative stress effects, anti-inflammatory response and regulation of cell proliferation and apoptosis, especially its modifications on TLR4/TRIF/NF-κB signaling pathway and p53-dependent cell cycle control and apoptosis. More studies are warranted to confirm its long-term efficacy and preventive role against malignant transformation of digestive precancerous lesions as evidence is insufficient. [ABSTRACT FROM AUTHOR]

Malaria is preventable, but the burden of disease remains high with over 249 million cases and 608,000 deaths reported in 2022. Historically, the most important protective interventions have been vector control and chemopreventive medicines with over 50 million children receiving seasonal malaria chemoprevention in the year 2023. Two vaccines are approved and starting to be deployed, bringing additional protection for children up to 36 months. However, the impact of these currently available tools is somewhat limited on various fronts. Vaccines exhibit partial efficacy, are relatively costly, and not accessible in all settings. The challenges encountered with chemoprevention are barriers to acceptability and feasibility, including frequency of dosing, and the lack of options in the first trimester of pregnancy and for women living with HIV. Also, the emergence of resistance against chemopreventive medicines is concerning. To address these limitations, a target product profile (TPP) is proposed as a road map to guide innovation and to boost the quest for novel chemopreventive alternatives. This TPP describes the ideal product attributes, while acknowledging potential trade-offs that may be needed. Critically, it considers the target populations most at risk; primarily infants, children, and pregnant women. Malaria control and elimination requires appropriate chemoprevention, not only in areas of high endemicity and transmission, but also in lower transmission areas where immunity is declining, as well as for travellers from areas where malaria has been eliminated. New medicines should show acceptable safety and tolerability, with high and long protective efficacy. Formulations and costs need to support operational adherence, access, and effectiveness. Next generation long-acting oral and injectable drugs are likely to constitute the backbone of malaria prevention. Therefore, the perspectives of front-line experts in malaria prevention, researchers, and those involved in drug development are captured in the TPP. This inclusive approach aims at concentrating efforts and aligning responses across the community to develop new and transformative medicines. [ABSTRACT FROM AUTHOR]

Seasonal Malaria Chemoprevention consisting of monthly administration of amodiaquine/sulfadoxine-pyrimethamine to children aged 3–59 months during the transmission season could promote SP-resistance. Mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes were assessed before and after SMC adoption in Burkina Faso. A total of 769 dried blood spots were selected from studies conducted in Nanoro, Burkina Faso, between 2010 and 2020. Of those, 299 were pre-SMC (2010–2012) and 470 were post-SMC-samples. Pfdhps and Pfdhfr genes were PCR-amplified and sequenced. A systematic review/meta-analysis of published studies conducted in Burkina Faso (2009–2023) was additionally performed. In Nanoro, the prevalence of Pfdhfr triple mutations (CIRNI) rose from 43.6% pre-SMC to 89.4% post-SMC (p < 0.0001). There was no mutation in Pfdhfr 164 and Pfdhps 540; Pfdhps A437G mutation increased from 63.9% (2010–2012) to 84.7% (2020) (p < 0.0001). The VAGKGS haplotype was 2.8% (2020). Pfdhfr/Pfdhps quintuple mutant IRN-436A437G rose from 18.6% (2010–2012) to 58.3% (2020) (p < 0.0001). Meta-analysis results from Burkina Faso showed an increase in mutations at Pfdhfr N51I, C59R, S108N, and Pfdhps A437G after SMC adoption. Post-SMC, the pyrimethamine-resistance marker prevalence increased, while the sulfadoxine-resistance marker prevalence remained stable. Detection of emerging PfdhpsVAGKGS haplotypes in 2020 underscores the importance of continuous SP-resistance monitoring. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Design and Setting Main Outcome Measures Results Conclusion Acute otitis media (AOM) is a common childhood infection. Recurrent AOM affects a subset of children, resulting in an adverse impact on quality of life, socioeconomic disadvantage, and risk of long‐term sequelae. Antimicrobial chemoprophylaxis is used in some settings but is increasingly controversial due to an awareness of adverse long‐term effects and contribution to global antibiotic resistance.A comprehensive literature search was undertaken using Medline (1946–October 2023) and Embase (1974–October 2023). The primary aim was to assess the efficacy of antimicrobial chemoprophylaxis on AOM episodes in children < 18 years of age. Bias and quality assessment was performed. Dichotomous data were analysed using risk ratio with 95% confidence intervals. Meta‐analysis was carried out using random‐effects models for pooled analysis, independent of heterogeneity. Heterogeneity was assessed using the I2 statistic.The effect of antimicrobial chemoprophylaxis in children with rAOM on the number of individual AOM episodes. Secondary outcomes: assessment of antimicrobial agents and outcomes in children with risk factors.Assessment of qualitative data was performed on 20 studies (n = 2210). No controlled trials were identified post‐multivalent pneumococcal conjugate vaccine (PCV) introduction, restricting current generalisability. Quantitative meta‐analysis on nine pre‐PCV studies (n = 1087) demonstrated antimicrobial chemoprophylaxis reduced any episode of AOM with a risk ratio 0.59 (95% CI 0.45–0.77).Families and clinicians must balance marginal short‐medium term benefit (based on pre‐PCV data), and the potential for adverse effects to that individual, and the societal risk of antimicrobial resistance with prolonged antibiotic use. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P <.01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% (P =.002), with the trauma and acute care surgery (TACS) show an increase of 6.6% (P <.001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% (P =.002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients. [ABSTRACT FROM AUTHOR]

The resistance of colorectal cancer (CRC) to conventional therapeutic modalities, such as radiation therapy and chemotherapy, along with the associated side effects, significantly limits effective anticancer strategies. Numerous epigenetic investigations have unveiled that naturally occurring stilbenes can modify or reverse abnormal epigenetic alterations, particularly aberrant DNA methylation status, offering potential avenues for preventing or treating CRC. By modulating the activity of the DNA methylation machinery components, phytochemicals may influence the various stages of CRC carcinogenesis through multiple molecular mechanisms. Several epigenetic studies, especially preclinical research, have highlighted the effective DNA methylation modulatory effects of stilbenes with minimal adverse effects on organisms, particularly in combination therapies for CRC. However, the available preclinical and clinical data regarding the effects of commonly encountered stilbenes against CRC are currently limited. Therefore, additional epigenetic research is warranted to explore the preventive potential of these phytochemicals in CRC development and to validate their therapeutic application in the prevention and treatment of CRC. This review aims to provide an overview of selected bioactive stilbenes as potential chemopreventive agents for CRC with a focus on their modulatory mechanisms of action, especially in targeting alterations in DNA methylation machinery in CRC. [ABSTRACT FROM AUTHOR]

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration [ABSTRACT FROM AUTHOR]

Malaria Consortium supports delivery of seasonal malaria chemoprevention (SMC) to children ages 3–59 months using sulfadoxine–pyrimethamine plus amodiaquine. Lot quality assurance sampling (LQAS) was adapted as a cost-efficient method for end-of-cycle SMC monitoring surveys across supported countries and an implementation challenges reporting system was established in Nigeria. We present a case study of its application in Nasarawa State. LQAS facilitated timely local performance assessment across 16 indicators. Development of new reporting tools has played a key role in stimulating national-level discussions on improvements to SMC supervisory processes and implementer training and provided a framework for engagement with local stakeholders. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) accounts for roughly 85% of all malignant kidney cancer. Therapeutic options for RCC have expanded rapidly over the past decade. Targeted therapy and immunotherapy have ushered in a new era of the treatment of RCC, which has facilitated the outcomes of RCC. However, the related adverse effects and drug resistance remain an urgent issue. Natural compounds are optional strategies to reduce mobility. Natural compounds are favored by clinicians and researchers due to their good tolerance and low economic burden. Many studies have explored the anti‐RCC activity of natural products and revealed relevant mechanisms. In this article, the chemoprevention and therapeutic potential of natural compounds is reviewed and the mechanisms regarding natural compounds are explored. [ABSTRACT FROM AUTHOR]

Mental health and HIV risk behavior have been studied with ecological momentary assessment (EMA), but this approach has not been combined with tracking of activity space (where people go and what they encounter there) in people with HIV and their social relations, who may be HIV+ or HIV−. Activity space represents a modifiable risk or protective factor for behavior related to health status and quality of life, in both clinical and nonclinical populations. We conducted an observational study with 286 participants (243 HIV+ and 43 HIV−), roughly matched for socioeconomic status and neighborhood of residence via three waves of snowball sampling. Each participant carried a smartphone for up to 4 weeks, making 5 randomly prompted entries and 1 end-of-day entry each day, plus self-initiated event-contingent entries for sexual activity and drug use. Responses to randomly prompted items provided subjective evaluations of the safety of the participant's current social and physical environment (the place they were and the people they were with). GPS-based location tracking—coupled with publicly available statistic indicating neighborhood-level physical disorder and socioeconomic disadvantage—provided an indicator of each participant's exposure to objective psychosocial hazard. We examined possible relationships of these objective and subjective environmental exposures with risky sexual and intravenous drug-use behavior, knowledge and utilization of antiretroviral treatment and prophylaxis, and momentary mental health (mood and stress, which relate to risky behavior and overall well-being). We found that both risky behavior and mental health were more related to participants' subjective evaluations of their activity space than to objective measures of neighborhood-level disorder, suggesting that, even within an objectively hazardous neighborhood, people who find a niche they perceive as socially and physically safe may engage in less risky behavior and have better well-being. Trial registration Clinicaltrials.gov Identifier NCT01571752. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore molecular measures of P. falciparum malaria burden (FOI and MOI) in the context of seasonal malaria chemoprevention. We analyzed malaria cases collected as part of a longitudinal cohort study. The cohort included P. falciparum-negative children aged 1.5 to 12, as confirmed by PCR 21 days after a radical cure using DHA-PQ or AS. Children were followed up for six months using active and passive case detection methods. At each visit, dried blood spots and blood smears were collected by finger prick, along with clinical data. Parasite DNA was extracted and analyzed by nested PCR for detection and genotyping of P. falciparum parasites. A total of 458 P. falciparum isolates collected during follow-up from October 2020 to March 2021 were genotyped. During the follow-up, children contracted 1.05 (95% IC [0.81–1.30]) new P. falciparum infections/child/time of exposure, and the MOI value was 3.00 (SD 1.60). Age is a protective factor (IRR: 0.74; 95% CI: 0.61, 0.90) against the occurrence of an episode of malaria, unlike an increase in MOI (IRR: 1.63; 95% CI: 1.04, 1.99), which is a favorable factor (p < 0.05). This study confirms the reduction in malaria transmission in our study area, probably due to the massive deployment of control tools. [ABSTRACT FROM AUTHOR]

Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by in vitro kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models in vivo. Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization 2022 malaria chemoprevention guidelines recommend providing a full course of antimalarial treatment at pre-defined intervals, regardless of malaria status to prevent illness among children resident in moderate to high perennial malaria transmission settings as perennial malaria chemoprevention (PMC) with sulfadoxine-pyrimethamine (SP). The dhps I431V mutation circulating in West Africa has unknown effect on SP protective efficacy. Methods: This protocol is for a three-arm, parallel, double-blinded, placebo-controlled, randomised trial in Cameroon among children randomly assigned to one of three directly-observed treatment groups: (i) Group 1 (n = 450) receives daily artesunate (AS) placebo on days − 7 to -1, then active SP plus placebo amodiaquine (AQ) on day 0, and placebo AQ on days 1 and 2; (ii) Group 2 (n = 250) receives placebo AS on days − 7 to -1, then active SP and AQ on day 0, and active AQ on days 1 and 2; and (iii) Group 3 (n = 200) receives active AS on days − 7 to -1, then placebo SP on day 0 and placebo AQ on days 0 to 2. On days 0, 2, 5, 7, and thereafter weekly until day 28, children provide blood for thick smear slides. Dried blood spots are collected on the same days and weekly from day 28 to day 63 for quantitative polymerase chain reaction (qPCR) and genotype analyses. Discussion: Our aim is to quantify the chemopreventive efficacy of SP, and SP plus AQ, and measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP chemoprevention. We will report unblinded results including: (i) time-to-parasite clearance among SP and SP plus AQ recipients who were positive on day 0 by qPCR and followed to day 63; (ii) mean duration of SP and SP plus AQ protection against infection, and (iii) mean duration of symptom-free status among SP and SP plus AQ recipients who were parasite free on day 0 by qPCR. Our study is designed to compare the 28-day follow-up of the new WHO malaria chemoprevention efficacy study protocol with extended follow-up to day 63. Trial registration: ClinicalTrials.gov NCT06173206; 15/12/2023. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AhR) is an environmentally sensitive transcription factor (TF) historically associated with carcinogenesis initiation via the activation of numerous carcinogens. Nowadays, the AhR has been attributed to multiple endogenous functions to maintain cellular homeostasis. Moreover, crosstalk, often reciprocal, has been found between the AhR and several other TFs, particularly estrogen receptors (ERs) and nuclear factor erythroid 2-related factor-2 (Nrf2). Adequate modulation of these signaling pathways seems to be an attractive strategy for cancer chemoprevention. Several naturally occurring and synthetically modified AhR or ER ligands and Nrf2 modulators have been described. Sulfur-containing derivatives of glucosinolates, such as indole-3-carbinol (I3C), and stilbene derivatives are particularly interesting in this context. I3C and its condensation product, 3,3′-diindolylmethane (DIM), are classic examples of blocking agents that increase drug-metabolizing enzyme activity through activation of the AhR. Still, they also affect multiple essential signaling pathways in preventing hormone-dependent cancer. Resveratrol is a competitive antagonist of several classic AhR ligands. Its analogs, with ortho-methoxy substituents, exert stronger antiproliferative and proapoptotic activity. In addition, they modulate AhR activity and estrogen metabolism. Their activity seems related to a number of methoxy groups introduced into the stilbene structure. This review summarizes the data on the chemopreventive potential of these classes of phytochemicals, in the context of AhR and its crosstalk modulation. [ABSTRACT FROM AUTHOR]

Simple Summary: Natural polyphenols are well-known dietary supplements that have been used for medical purposes for a long time. Consuming foods and beverages of plant origin, especially those rich in polyphenolic compounds, may have chemopreventive and therapeutic effects on cancer due to the health-promoting properties of these compounds. Polyphenols are characterized by high structural diversity, which contributes to their wide range of therapeutic effects, including anti-oxidant and anti-cancer activities. These compounds can modulate the expression and activity of many proteins, including enzymes, and regulate multiple cell signaling pathways. Among the molecular targets of anti-cancer agents are matrix metalloproteinases, particularly metalloproteinase-2 and metalloproteinase-9, and nuclear factor-kappa B. Matrix metalloproteinases can degrade the protein components of the extracellular matrix and play key roles in physiological processes such as tissue repair and morphogenesis, as well as in carcinogenesis and other pathological processes. The inhibition of their synthesis and activity is closely related to a reduction in the metastasis and invasion of cancer cells. This review discusses the current state of knowledge concerning the anti-invasive and anti-metastatic potential of selected polyphenols, with a focus on in vitro and in vivo evidence. Polyphenols are natural compounds found in many plants and their products. Their high structural diversity bestows upon them a range of anti-inflammatory, anti-oxidant, proapoptotic, anti-angiogenic, and anti-metastatic properties, and a growing body of research indicates that a polyphenol-rich diet can inhibit cancer development in humans. Polyphenolic compounds may modulate the expression, secretion, or activity of compounds that play a significant role in carcinogenesis, including type IV collagenases, such as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), by suppressing cellular signaling pathways such as nuclear factor-kappa B. These enzymes are responsible for the degradation of the extracellular matrix, thus promoting the progression of cancer. This review discusses the current state of knowledge concerning the anti-cancer activity of polyphenols, particularly curcumin, resveratrol, epigallocatechin-3-gallate, genistein, and quercetin, with a specific focus on their anti-invasive and anti-metastatic potential, based on the most recent in vitro and in vivo studies. It appears that polyphenols may be valuable options for the chemoprevention and treatment of cancer via the inhibition of MMP-2 and MMP-9 and the suppression of signaling pathways regulating their expression and activity. [ABSTRACT FROM AUTHOR]

Background: Post-discharge malaria chemoprevention (PDMC) is an intervention aimed at reducing morbidity and mortality in patients hospitalized with severe anaemia, with its effectiveness established in several clinical trials. The aim of this study was to better understand factors that would influence the scale up of this intervention, and to identify preferences for two delivery mechanisms, facility-based or community-based. Methods: Forty-six qualitative individual interviews were conducted in five sub-Saharan countries amongst malaria key opinion leaders and national decision makers. Findings were analysed following a thematic inductive approach. Results: Half of participants were familiar with PDMC, with a satisfactory understanding of the intervention. Although PDMC was perceived as beneficial by most respondents, there was some unclarity on the target population. Both delivery approaches were perceived as valuable and potentially complementary. From an adoption perspective, relevant evidence generation, favorable policy environment, and committed funding were identified as key elements for the scale up of PDMC. Conclusions: The findings suggest that although PDMC was perceived as a relevant tool to prevent malaria, further clarification was needed in terms of the relevant patient population, delivery mechanisms, and more evidence should be generated from implementation research to ensure policy adoption and funding. [ABSTRACT FROM AUTHOR]

Background: Perennial malaria chemoprevention (PMC) is a chemoprevention strategy endorsed by the World Health Organization (WHO) and is increasingly being adopted by National Malaria Programmes. PMC aims to reduce morbidity and mortality caused by malaria and anaemia in in young children through provision of antimalarial drugs at routine contact points with the local health system. This study aims to evaluate the impact of the programmatically-implemented country-tailored PMC programmes targeting children up to two years of age using sulfadoxine-pyrimethamine (SP) on the incidence of malaria and anaemia in children in Cameroon and Côte d'Ivoire. Methods: We will assess the impact of PMC using passive and active monitoring of a prospective observational cohort of children up to 36 months of age at recruitment in selected study sites in Cameroon and Côte d'Ivoire. The primary and secondary outcomes include malaria, anaemia and malnutrition incidence. We will also conduct a time-series analysis of passively detected malaria and anaemia cases comparing the periods before and after PMC introduction. This study is powered to detect a 30% and 40% reduction of malaria incidence compared to the standard of care in Cameroon and Côte d'Ivoire, respectively. Discussion: This multi-country study aims to provide evidence of the effectiveness of PMC targeting children in the first two years of life on malaria and anaemia and will provide important information to inform optimal operationalization and evaluation of this strategy. Trial Registration: Cameroon - NCT05889052; Côte d'Ivoire - NCT05856357. [ABSTRACT FROM AUTHOR]

Patients with severe burn injuries are at risk of venous thromboembolism (VTE) and associated sequelae. Burn-injured patients may require larger doses of VTE prophylaxis so underdosing may occur with standard regimens. Monitoring anti-factor Xa (AFXa) levels may allow tailoring of dosage but is currently uncommon. The purpose of this systematic review was to methodically review the available literature with respect to AFXa in severe burn-injured patients, and thereby assess its efficacy. Using PRISMA guidelines, "Xa" and "burns" were used to systematically review MEDLINE (1946 - present) and EMBASE (1974 - present) databases for publications regarding the monitoring of AFXa levels for thromboprophylaxis in burn-injured patients. Eight studies (432 patients) met inclusion. Peak AFXa level at initial measurement was reported in all studies and was within the range for prophylaxis in 184 of 432 cases (42.6%), below range in 246 of 432 cases (56.9%) and above range for 2/432 (0.5%). Complications were reported in 7 studies (412 patients), with a total of 30 (7.3%) complications, comprising of 16 (53.3%) VTE events and 14 (46.7%) mortalities. Three studies comprising 270 patients compared complications between patients who were within the reference range with patients who were below the range. There were 164 patients from the 'within the reference range' groups that had a total of 6 (3.7%) complications, comprised of 4 (66.7%) VTE events and 2 (33.3%) mortalities. There were 106 patients from the 'below reference range group' that had a total of 11 (10.4%) complications, comprised of 9 (81.8%) VTE events and 2 (18.2%) mortalities. Our findings suggest standard prophylactic anticoagulation dosing risks underdosing and therefore, an increased risk in the development of VTE. AFXa monitoring allows individually tailored dose adjustment to reach therapeutic levels, which may be efficacious in reducing VTE events and is therefore recommended where possible. • Burn injured patients are at high risk of venous thromboembolism (VTE). • Underdosing of chemoprophylaxis frequently occurs in the burn-injured patient. • Anti-Xa monitoring allows tailoring of enoxaparin dosage. • Anti-Xa monitoring may reduce the frequency of VTE in burn patients. [ABSTRACT FROM AUTHOR]

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention. [ABSTRACT FROM AUTHOR]

The use of natural bioactive constituents from various food sources for anticancer purposes has become increasingly popular worldwide. Broccoli (Brassica oleracea var. italica) is on the top of the consumed vegetables by the masses. Its raw matrix contains a plethora of phytochemicals, such as glucosinolates and phenolic compounds, along with rich amounts of vitamins, and minerals. Consumption of broccoli-derived phytochemicals provides strong antioxidant effects, particularly due to its sulforaphane content, while modulating numerous molecules involved in cell cycle regulation, control of apoptosis, and tuning enzyme activity. Thus, the inclusion of broccoli in the daily diet lowers the susceptibility to developing cancers. Numerous studies have underlined the undisputable role of broccoli in the diet as a chemopreventive raw food, owing to the content in sulforaphane, an isothiocyanate produced as a result of hydrolysis of precursor glucosinolates called glucoraphanin. This review will provide evidence supporting the specific role of fresh florets and sprouts of broccoli and its key bioactive constituents in the prevention and treatment of different cancers; a number of studies carried out in the in vitro and in vivo conditions as well as clinical trials were analyzed. [ABSTRACT FROM AUTHOR]

Autologous breast reconstruction is considered high-risk for deep vein thrombosis (DVT) and thromboembolism (PE). It is therefore recommended to treat patients undergoing these complex and lengthy procedures with DVT chemoprophylaxis. The optimal anticoagulation protocol is still not established. The objective of our study was to evaluate the need of a prolonged anticoagulation in patients undergoing microsurgical breast reconstruction. This retrospective cohort study compares our former anticoagulation protocol, which was given during the in-hospital stay, with our new protocol consisting of extended anticoagulation until postoperative day 25, in terms of DVT/PE risk reduction. A logistic regression was used to evaluate the risk of DVT/PE between the two groups, while adjusting for several covariates. Our cohort consisted of 205 patients in the short-term anticoagulation group and 219 in the extended protocol group. Five patients (2.4%) in the short-term anticoagulation group had a DVT/PE event versus 4 patients (1.8%) in the extended protocol group. Logistic regression revealed no difference in the incidence of DVT/PE between the two groups. Similarly, there was no differences in terms of hematoma and infection rate between the two groups. Finally, we found an increased risk of DVT/PE in patients with a Caprini score equal or greater than 8. In our experience, short-term anticoagulation during the hospital stay is equivalent to extended thromboprophylaxis in terms of DVT/PE prevention. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65–0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69–0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86–0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90–1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC. [ABSTRACT FROM AUTHOR]

Oxysterols have been implicated in biliary tract cancer (BTC), and Niemann-Pick C1–like 1 (NPC1L1) has been associated with oxysterol uptake in biliary and intestinal cells. Thus, our study aims to investigate the potential causal link between genetically proxied NPC1L1 inhibitors and the risk of BTC. In this study, we employed two genetic instruments as proxies for NPC1L1 inhibitors, which included LDL cholesterol-associated genetic variants located within or in close proximity to the NPC1L1 gene, as well as expression quantitative trait loci (eQTLs) of the NPC1L1 gene. Effect estimates were calculated using the Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods. In MR analysis using the IVW method, both proxy instruments from the UK Biobank and the GLGC demonstrated a positive association between NPC1L1-mediated LDL cholesterol and BTC risk, with odds ratios (OR) of 10.30 (95% CI = 1.51–70.09; P = 0.017) and 5.61 (95% CI = 1.43–21.91; P = 0.013), respectively. Moreover, SMR analysis revealed a significant association between elevated NPC1L1 expression and increased BTC risk (OR = 1.19, 95% CI = 1.04–1.37; P = 0.014). This MR study suggests a causal link between NPC1L1 inhibition and reduced BTC risk. NPC1L1 inhibitors, like ezetimibe, show potential for chemoprevention in precancerous BTC patients, requiring further clinical investigation. [ABSTRACT FROM AUTHOR]

We investigated the benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer vs excess mortality from bleeding among Helicobacter pylori –eradicated patients, and its interaction with proton pump inhibitors (PPIs). H pylori –eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from the date of H pylori therapy until death or the end of the study (July 2020). Primary exposure was aspirin use as time-varying variable. The primary outcome was GI cancer–related (gastrointestinal, hepatobiliary, or pancreatic cancer) death and the secondary outcome was bleeding-related (gastrointestinal bleeding or intracranial bleeding) death. The adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities, and concomitant medications. The benefit-risk profile was expressed as the adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and nonusers. A total of 87,967 subjects were followed up for a median of 10.1 years, with 1294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer–related mortality (aHR, 0.51; 95% CI, 0.42–0.61), but higher bleeding-related mortality (aHR, 1.52; 95% CI, 1.11–2.08). Among PPI users, the aHR of bleeding-related mortality with aspirin was 1.06 (95% CI, 0.70–1.63). For the whole cohort, the adjusted absolute risk difference between aspirin users and nonusers was 7 (95% CI, 5–8) fewer cancer-related and 1 (95% CI, 0.3–3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95% CI, 8–10) fewer cancer-related deaths per 10,000 person-years without an increase in bleeding-related deaths. GI cancer mortality benefit from aspirin outweighs bleeding-related mortality in H pylori –eradicated subjects, which is enhanced further by PPI use. [ABSTRACT FROM AUTHOR]

Background and Purpose: Powe conceptually defined "cancer fatalism" and developed the Powe Fatalism Inventory (PFI) to operationalize cancer fatalism. Researchers report disparate underlying factor structures, and sparse evidence supports the validity and reliability of the PFI. Therefore, the purpose of this study was to examine the psychometric properties of the PFI. Specifically, we aimed to examine its (a) underlying dimensions, (b) internal consistency, and (c) construct validity. Methods: We recruited 400 post-menopausal women, 50–64 years old, for a study on mammographic breast density. Women completed the 15-item PFI and the 8-item Champion Breast Cancer Fear Scale (CBCFS). We conducted item analyses and exploratory factor analysis and evaluated different factor structures. We estimated internal consistency and conducted Pearson correlations between PFI and CBCFS scores to examine construct validity. Results: We found a two-factor solution. Factor 1, Predetermination, had an eigenvalue of 5.2 and explained 43% of the variance with factor loadings ranging from −0.59 to −0.83. Factor 2, Pessimism, had an eigenvalue of 4.5 and explained 15.2% of the variance with factor loadings ranging from 0.63 to 0.77. Both factors together explained 58.2% of the variance. There were no cross-loading items and no item loadings below 0.4. The two subscales both had alphas of.89. Cancer fatalism scores were positively related to fear scores (r =.317, p <.001, 95% CI: 0.222, 0.406). Conclusion: Using PFI responses from postmenopausal women, we determined that the two-factor solution was the most parsimonious yet theoretically sound factor structure underlying the 15 items of the PFI. The subscales Predetermination (Factor 1; six items) and Pessimism (Factor 2; nine items) were internally consistent with the evidence of the construct validity. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management. Recent Findings: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs. Summary: The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: Premedication, including a histamine-1 receptor (H1) antagonist, is recommended to all patients treated with paclitaxel chemotherapy to reduce the incidence of hypersensitivity reactions (HSRs). However, the scientific basis for this premedication is not robust, which provides opportunities for optimization. Substitution of intravenously administered first-generation H1 antagonist for orally administered second-generation H1 antagonist could reduce side effects, and improve efficiency and sustainability. This study investigates the efficacy and safety of substituting intravenous clemastine for oral cetirizine as prophylaxis for paclitaxel-induced HSRs. METHODS: This single-center, prospective, noninferiority study compares a historic cohort receiving a premedication regimen with intravenous clemastine to a prospective cohort receiving oral cetirizine. Primary end point of the study is HSR grade ≥3. The difference in incidence was calculated together with the 90% CI. We determined that the two-sided 90% CI of HSR grade ≥3 incidence in the oral cetirizine cohort should not be more than 4% higher (ie, the noninferiority margin) compared with the intravenous clemastine cohort. RESULTS: Two hundred and twelve patients were included in the oral cetirizine cohort (June 2022 and May 2023) and 183 in the intravenous clemastine cohort. HSR grade ≥3 incidence was 1.6% (n = 3) in the intravenous clemastine cohort and 0.5% (n = 1) in the oral cetirizine cohort, resulting in a difference of –1.2% (90% CI, –3.4 to 1.1). CONCLUSION: Premedication containing oral cetirizine is as safe as premedication containing intravenous clemastine in preventing paclitaxel-induced HSR grade ≥3. These findings could contribute to optimization of care for patients and improve efficiency and sustainability. Oral cetirizine is a nonsedative, easy, and effective alternative for IV antihistamines before paclitaxel. [ABSTRACT FROM AUTHOR]

(1) Background: Lower gastrointestinal bleeding (LGIB) accounts for 20% of all gastrointestinal bleeds. LGBI originates in the colon, rectum, and anus, mainly in patients who are receiving antiaggregant or anticoagulant treatment. The major causes are diverticular disease, colitis, hemorrhoids, and angiodysplasia. The literature studies underline that Direct Oral Anticoagulants (DOACs) are effective in reducing the risk of thromboembolic events but are associated with a higher risk of lower gastrointestinal bleeding (LGIB), particularly lower hemorrhoid bleeding. (2) Methods: The aim of our review is to revise the risk of hemorrhoid bleeding, pathophysiology, and management in patients taking DOACs in light of the most modern evidence. (3) Conclusions: central to the management of hemorrhoid bleeding in patients receiving DOAC therapy is the consideration of a tailored approach that respects the delicate equilibrium between the need for thromboembolic prophylaxis and the potential for bleeding complications. Cessation of anticoagulation, if clinically feasible, constitutes a fundamental cornerstone in the control of hemorrhage. This pause in therapy aims to mitigate the exacerbation of bleeding risk while offering a window for the implementation of local measures to manage hemorrhoid bleeding. [ABSTRACT FROM AUTHOR]

Abstract Raspberries (RBs) (Rubus idaeus) are rich in bioactive compounds with promising anticancer properties. This review provides a comprehensive analysis of the anticancer effects of RBs, highlighting their potential as natural agents in cancer prevention and therapy. Bioactive compounds in RBs induce apoptosis, arrest the cell cycle, inhibit angiogenesis, and suppress metastasis. Preclinical studies demonstrate significant anticancer effects against colon, breast, lung, prostate, and cervical cancers, with clinical studies also supporting their therapeutic potential. Although preclinical findings are encouraging, further large‐scale clinical trials are needed to confirm their efficacy and safety in humans. Optimizing formulations to enhance bioavailability and therapeutic effectiveness is crucial. This review emphasizes the potential of dietary interventions involving RBs as a complementary approach to conventional cancer therapies, paving the way for future research and clinical innovations.

Abstract Malaria is preventable, but the burden of disease remains high with over 249 million cases and 608,000 deaths reported in 2022. Historically, the most important protective interventions have been vector control and chemopreventive medicines with over 50 million children receiving seasonal malaria chemoprevention in the year 2023. Two vaccines are approved and starting to be deployed, bringing additional protection for children up to 36 months. However, the impact of these currently available tools is somewhat limited on various fronts. Vaccines exhibit partial efficacy, are relatively costly, and not accessible in all settings. The challenges encountered with chemoprevention are barriers to acceptability and feasibility, including frequency of dosing, and the lack of options in the first trimester of pregnancy and for women living with HIV. Also, the emergence of resistance against chemopreventive medicines is concerning. To address these limitations, a target product profile (TPP) is proposed as a road map to guide innovation and to boost the quest for novel chemopreventive alternatives. This TPP describes the ideal product attributes, while acknowledging potential trade-offs that may be needed. Critically, it considers the target populations most at risk; primarily infants, children, and pregnant women. Malaria control and elimination requires appropriate chemoprevention, not only in areas of high endemicity and transmission, but also in lower transmission areas where immunity is declining, as well as for travellers from areas where malaria has been eliminated. New medicines should show acceptable safety and tolerability, with high and long protective efficacy. Formulations and costs need to support operational adherence, access, and effectiveness. Next generation long-acting oral and injectable drugs are likely to constitute the backbone of malaria prevention. Therefore, the perspectives of front-line experts in malaria prevention, researchers, and those involved in drug development are captured in the TPP. This inclusive approach aims at concentrating efforts and aligning responses across the community to develop new and transformative medicines.

Abstract The escalating global cancer burden underscores the urgent need for more effective therapeutic strategies. Phytochemicals, naturally occurring compounds in plants, have garnered attention for their potential in cancer chemoprevention and chemotherapy. Their ability to modulate molecular mechanisms and influence cell signaling pathways offers a promising avenue for cancer management. This review aims to synthesize current knowledge on phytochemicals’ chemopreventive and chemotherapeutic potential, focusing on their molecular mechanisms of action and impacts on cell signaling pathways involved in cancer. A systematic literature search was conducted across major databases, including PubMed/Medline, Web of Science, Scopus, and Google Scholar. The search strategy uses Medical Subject Headings (MeSH) and free‐text terms using Boolean operators to capture relevant studies. Inclusion criteria targeted original research and reviews on the effects of phytochemicals in cancer, with a specific focus on molecular mechanisms. Phytochemicals, including flavonoids, polyphenols, and terpenoids, demonstrated significant anticancer properties by inducing cell cycle arrest, apoptosis, and autophagy. They modulate critical cell signaling pathways, such as cyclooxygenase‐2, nuclear factor kappa B, and various growth factor‐related pathways, and rectify epigenetic alterations, contributing to their chemopreventive and therapeutic effects. Phytochemicals represent a valuable resource for developing novel cancer prevention and treatment strategies; their actions on molecular mechanisms and cell signaling pathways underscore their potential in cancer prevention and combat. Further research is warranted to translate these findings into clinical applications, optimizing phytochemical‐based interventions for cancer management.

The basis for the prevention of cancer is the correction of initial epigenetic disorders in the cell, i.e. implementation of pathological genome reversion. Convincing evidence has accumulated to support the potential antitumor activity of compounds derived from cruciferous vegetables of the genus Brassicaceae. Indole-3-carbinol and 3,3'-diindolylmethane (DIM) have been investigated for their use as chemopreventive agents. DIM is formed in the acidic environment of the stomach as a result of dimerization of indole-3-carbinol monomers. Currently, it is impossible to identify a specific vector of influence of DIM at the molecular level. In this review, we summarize the pleiotropic effects of DIM aimed at correcting reversible epigenetic changes in tumor cells. Emphasis will be placed on the major cellular and molecular events that are effectively modulated by DIM. The main profile of DIM competencies concerns the management of intracellular signal transmission and correction of initial molecular genetic changes at the level of key participants in signaling pathways (NF-κB/Wnt/Akt/mTOR) leading to the development of cancer. The ability of DIM to differentially modulate tumor cell apoptosis has been observed in preclinical studies. It has been suggested that using DIM it is possible to increase the effectiveness of chemotherapeutic compounds with different molecular targets, thereby increasing chemosensitization. DIM has entered phase III clinical trials, with preliminary results confirming its promise both as a stand-alone drug and in combination with other components of anticancer therapy. Establishing the range of epigenetic control of DIM molecular and genetic changes in various cancers will allow optimization of therapeutic epigenetics approaches.

BACKGROUND: Despite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children 3-59 months of age in Burkina Faso, malaria incidence remains high, raising concerns regarding SMC effectiveness and selection of drug resistance. Using a case-control design, we determined associations between SMC drug levels, drug resistance markers, and presentation with malaria. METHODS: We enrolled 310 children presenting at health facilities in Bobo-Dioulasso. Cases were SMC-eligible children 6-59 months of age diagnosed with malaria. Two controls were enrolled per case: SMC-eligible children without malaria; and older (5-10 years old), SMC-ineligible children with malaria. We measured SP-AQ drug levels among SMC-eligible children and SP-AQ resistance markers among parasitemic children. Conditional logistic regression was used to compute odds ratios (ORs) comparing drug levels between cases and controls. RESULTS: Compared to SMC-eligible controls, children with malaria were less likely to have any detectable SP or AQ (OR, 0.33 [95% confidence interval, .16-.67]; P = .002) and have lower drug levels (P < .05). Prevalences of mutations mediating high-level SP resistance were rare (0%-1%) and similar between cases and SMC-ineligible controls (P > .05). CONCLUSIONS: Incident malaria among SMC-eligible children was likely due to suboptimal levels of SP-AQ, resulting from missed cycles rather than increased antimalarial resistance to SP-AQ.

PurposeChemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation.MethodsWe conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.ResultsThere were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07).ConclusionChemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

Watercress (Nasturtium officinale R. Br.; Brassicaceae) is a highly nutritious leafy green vegetable consumed globally, with a rich health-related phytonutrient profile that includes the secondary plant metabolites glucosinolates (GLS), especially gluconasturtiin and its hydrolysis product phenethyl isothiocyanate (PEITC). The peppery taste and pungency of watercress comes from these mustard oils, and they are known to help reduce inflammation and chronic damage in cells and have been shown to have a role in cancer prevention in vitro and in vivo. We explored how both genotype and highly contrasting environments of California (CA) and the United Kingdom (UK) alter phenotypic traits for a set of F2:4 genotypes created from a unique bi-parental cross, chosen for their extreme phenotypes for yield, leaf and branch morphology, antioxidant capacity, and glucosinolate content in two contrasting field locations. Although both genotype and environment had a significant impact on plant morphology, nutritional quality, and yield, overall, the highly contrasting environments of California and the UK, had a much stronger effect. Plants grown in CA had higher biomass, thicker main stem and more branches, and a higher concentration of aromatic GLS, whilst plants grown in the UK had larger leaves with longer stems, suggesting a better harvestable product, at least for a salad and not a soup crop. Significant G x E interactions were observed for multiple traits, suggesting significant phenotypic plasticity of watercress and variation between genotypes that will enable the selection of ideotypes suitable for these highly contrasting growth environments, that can be considered as the ‘extremes’ of an environmental gradient where the crop might be grown, from the warm and dry soil-grown conditions of California to the relatively cool and wet aquatic growing system of the UK.