Acute and chronic exposure to pesticides is associated with several negative effects on human health, such as an increased risk of cancer, including mature B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). However, the biological mechanism linking pesticide exposure to the development of CLL and MM has not yet been elucidated. Thus, this study aimed to explore miRNA expression profiles in patients with CLL and MM who were occupationally exposed and not exposed to pesticides. For this purpose, 24 patients with MM and CLL were recruited from a cohort in Brazil and the miRNA expression profiles between the groups were analyzed using Nanostring technology. The study revealed the downregulation of miR-423-3p, miR-1193, miR-576-5p, miR-509-5p, miR-548b-3p, miR-1469, miR-329-3p, and miR-548j-3p, and the upregulation of miR-301b-5p and miR-548ah-5p in patients with CLL and MM were associated with occupational exposure to pesticides. The integrated network analysis of the differentially expressed miRNAs and their target genes in the exposed group demonstrated that miRNAs can participate in the regulation of signaling pathways, such as PI3K/Akt/mTOR and MAPK. Additionally, these miRNAs were found to be associated with an increased risk of developing neurological diseases and various types of cancer. In the present study, we demonstrate, for the first time, altered expression of plasma-derived miRNAs in patients with CLL and MM exposed to pesticides. The plasma miRNAs identified may serve as promising candidates for biomarkers of pesticides effects, potentially contributing to the emerging field of Precision Environmental Health.

Preeclampsia is now acknowledged as a systemic disorder with long-term implications for maternal and offspring health, reframing it as a sentinel event that reveals underlying vulnerabilities and signals future risk of cardiovascular, hypertensive, and kidney diseases in both mother and child. The "children of preeclampsia" should be on our radars as a population warranting early attention, shaping new standards of disease prevention.

Targeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly EGFR-mutant and ALK-rearranged tumors, have become the standard of care across nearly all stages of the disease. However, the arbitrarily defined dose and treatment duration of TT, as well as the financial cost of these drugs, reduce their availability worldwide. Pharmacokinetic and pharmacodynamic properties of TT suggest that doses of some TT are overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. Some academic initiatives have been launched aiming to explore de-escalating strategies with TT, either reducing the dose or the duration of these drugs. These approaches can decrease the risk of adverse events positively impacting patients' quality of life, without compromising efficacy, while reducing economic impact. In this review, we summarize current data regarding de-escalating strategies with TT, ongoing trials and challenges of this approach.

Plasma ceramides (Cer) are associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). We examined whether a newly developed plasma ceramide-based risk score (CER24 score) performs better than CERT1 risk score in predicting adverse cardiovascular outcomes in patients with known or suspected CAD.

We followed 167 ambulatory patients undergoing stress myocardial perfusion scintigraphy (MPS) for clinical reasons for a median of 6 years. For the CER24 risk score calculation, we measured plasma Cer(d16:1/24:1)/Cer(d16:1/24:0), Cer(d18:0/24:1)/Cer(d18:0/24:0), Cer(d18:1/24:1)/Cer(d18:1/24:0), Cer(d18:2/24:1)/Cer(d18:2/24:0), and Cer(d20:1/24:1)/Cer(d20:1/24:0), both before and after stress MPS, using a targeted liquid chromatography-tandem mass spectrometry assay. Pre-stress CER24 risk categories (high vs. low/moderate risk) at baseline were associated with a ∼3-fold higher risk of developing the primary composite outcome (defined as all-cause mortality or nonfatal myocardial infarction) even after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted-hazard ratio 3.06, 95 %CI 1.63-5.77; p = 0.001). Post-stress CER24 risk categories yielded similar results. CER24 high-risk category performed better than CERT1 high-risk category in predicting the primary composite outcome (AUCs = 0.647 vs. 0.580; p = 0.048).

The CER24 score is associated with a higher risk of the composite outcome and performs better than CERT1 score in predicting the risk of dying or developing nonfatal cardiovascular events.

A man in his 60s presented with severe abdominal pain, vomiting and obstipation for the last 2 days. His examination revealed a tender abdomen. The contrast-enhanced CT of the abdomen reported superior mesenteric artery thrombosis with ischaemic changes in the bowel. After initial resuscitation, an exploratory laparotomy was done, revealing a gangrenous small bowel of 323 cm, which was resected, and a double-barrel jejuno-ileostomy was performed. Postoperatively, total parenteral nutrition was started and gradually replaced with oral supplements and refeeding of bowel contents. One week after discharge, the patient presented with features of severe dehydration and short bowel syndrome. After resuscitation and stabilisation, restoration of bowel continuity was performed. The patient developed the refeeding syndrome postsurgery, which was managed with micronutrient supplementation. This case highlights the challenges of managing a patient with short bowel syndrome, including timely surgical intervention, postoperative monitoring and appropriate nutritional management for the best outcome.

A late-adolescent female presented with sudden-onset, painless diminution of vision in her left eye, with multiple treatment interventions and recurrences of symptoms, over one year. She was diagnosed with left eye central retinal vein occlusion (CRVO) and was given eight intravitreal anti-vascular endothelial growth factor (VEGF) (ranibizumab) injections elsewhere, with only transient improvement followed by recurrence of retinal haemorrhages and macular oedema. Considering her young age and absence of typical risk factors, a detailed infectious, autoimmune and hematologic workup was performed. A detailed thrombophilia panel revealed reduced free protein S activity (14%) and C4b complement levels, indicating an inherited thrombophilic state. A history of recurrent pregnancy loss in her grandmother hinted at a prothrombotic predisposition. She was started on oral warfarin and injected with two additional anti-VEGF injections to manage existing macular edema. Her visual acuity remained stable with no recurrence of macular oedema over a one-year follow-up, highlighting the importance of comprehensive evaluation in young CRVO patients and importance of systemic therapy in combination with ocular therapy in successful clinical management and sustained outcomes.

Still's disease is an inflammatory syndrome affecting patients across all ages, previously known as systemic juvenile idiopathic arthritis (sJIA) in children and adult-onset Still's disease (AOSD) in adults. Multiple lines of evidence reported overlapping clinical features between sJIA and AOSD, commonly manifesting with daily fever, arthritis, evanescent salmon-coloured skin rash. The concomitant various degree of multiorgan involvement may increase the heterogeneity of the patient clinical picture. In active patients, a typical hyperferritinemia is recognized in association with increases of erythrocyte sedimentation rate and C reactive protein. Concerning pathogenesis, also in this case, similar mechanisms are reported in sJIA and AOSD involving both innate and adaptive arms of the immune systems; thus, Still's disease is peculiarly codified at the cross-road of autoinflammatory and autoimmune disorders. Furthermore, life-threatening complications burden the disease course in challenging the management of these patients, mainly macrophage activation syndrome, and worsening the prognosis. Concerning the treatment, glucocorticoids (GCs), conventional synthetic disease-modifying anti rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs), mainly IL-1 inhibitors, are administered to treat these patients. Usually, bDMARDs are considered in case of failure of GCs or GC-dependence. However, in some circumstances, bDMARDs may be administered as first-line modifying therapy without GCs, thus avoiding GC predictable side effects and optimizing the long-term outcome. In this work, we aimed to synthetize the recent available literature considering the clinical management of patients with Still's disease, reviewing features about early diagnosis, optimal treatment algorithm, clinical therapeutic targets, treatment of complications, and patient monitoring in the follow-up.

Under normal physiological conditions, the body operates through the intricate coordination of multiple organs, with the heart serving as a central energy engine that communicates with other organs. Conversely, both physiological and pathological states can influence cardiac activity via neural and humoral regulation. Extracellular vesicles (EVs) are nanoscale, lipid-bound particles secreted by nearly all cell types. These vesicles are rich in proteins, lipids, sugars, and genetic material, facilitating intercellular communication. EVs achieve this by fusing with or being endocytosed by recipient cells, thereby transferring bioactive molecules. While considerable research has explored the role of EVs in inter-organ communication, the specific mechanisms by which EVs link the cardiovascular system to other organs remain insufficiently understood. This review aims to elucidate the critical function of extracellular vesicles in bridging the cardiovascular system and other organs, with particular emphasis on intracardiac communication and major inter-organ communication pathways, providing a comprehensive analysis of recent findings in this evolving area of study.

Most cognitive studies of bipolar disorder (BD) have examined case-control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure.

Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version.

BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity.

IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.

We respond to articles in the Child and Adolescent Mental Health journal about whether, and under what, conditions researchers should collaborate with digital companies. In particular, we discuss the challenges academics face to access and study platform data. Independent academic research in this area is crucial for identifying and combating any potential negative effects that platforms can have on individuals and societies. Past discussions on academic data access have focused on platform regulation and data governance. However, in this commentary, we argue that even if key stakeholders agree on a regulatory and governance model, platforms have strong incentives to not comply-or to comply only partially. We advocate for a more holistic strategy aiming at influencing regulation, public opinion, news media, diverse political groups and for building a robust oversight structure.