Correlation Between Tacrolimus Levels in Blood Samples Obtained from Central Catheter and Peripheral Venipuncture in Lung Transplant Patients (Ven-Cat Study).

BACKGROUND: Following lung transplantation (LT), receiving immunosuppressive therapy is crucial. Tacrolimus is considered a drug with a narrow therapeutic range and its use requires constant monitoring. This study aimed to evaluate the correlation between tacrolimus levels obtained from central venous catheter and direct venipuncture in adult patients undergoing LT. METHODS: This prospective study included LT patients hospitalized in conventional ward carrying a central catheter through which no intravenous tacrolimus was administered. Trough samples were obtained through direct puncture and from the central catheter. Pearson correlation coefficient was calculated to quantify the mean difference between the 2 measures. RESULTS: A total of 54 sample pairs from 16 LT patients were obtained, mostly male (81.3%) and bilateral transplant recipients (93.8%); the transplant procedure was the primary reason for admission (81.3%). The difference in tacrolimus levels between both samples was 0.3 (0.1-0.6) mcg/L, with the measurement for the samples obtained through venipuncture being mostly higher than that for those obtained from the catheter. A strong correlation was observed between the tacrolimus levels in the samples obtained from the catheter and through venipuncture (Pearson correlation coefficient, 0.991; P < 0.001; R2 = 0.982). CONCLUSIONS: There is an excellent correlation between tacrolimus levels obtained from venipuncture and those obtained from central venous catheter in LT patients undergoing oral tacrolimus therapy.

Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment. Exposure of two CRAB clinical isolates, AB5075 and AMA40, to human urine (HU) resulted in the differential expression levels of 264 and 455 genes, respectively, of which 112 were common to both strains. Genes within this group play roles in metabolic pathways such as phenylacetic acid (PAA) catabolism, the Hut system, the tricarboxylic acid (TCA) cycle, and other processes like quorum sensing and biofilm formation. These results indicate that the presence of HU induces numerous adaptive changes in gene expression of the infecting bacteria. These modifications presumably help bacteria establish and thrive in the hostile conditions in the urinary tract. These analyses advance our understanding of CRAB's metabolic adaptations to human fluids, as well as expanding knowledge on bacterial responses to distinct human fluids containing different concentrations of human serum albumin (HSA).

Genomic Gigantism is not Associated with Reduced Selection Efficiency in Neotropical Salamanders.

Genome size variation in eukaryotes has myriad effects on organismal biology from the genomic to whole-organism level. Large genome size may be associated with lower selection efficiency because lower effective population sizes allow fixation of deleterious mutations via genetic drift, increasing genome size and decreasing selection efficiency. Because of a hypothesized negative relationship between genome size and recombination rate per base pair, increased genome size could also increase the effect of linked selection in the genome, decreasing the efficiency with which natural selection can fix or remove mutations. We used a transcriptomic dataset of 15 and a subset of six Neotropical salamander species ranging in genome size from 12 to 87 pg to study the relationship between genome size and efficiency of selection. We estimated dN/dS of salamanders with small and large genomes and tested for relaxation of selection in the larger genomes. Contrary to our expectations, we did not find a significant relationship between genome size and selection efficiency or strong evidence for higher dN/dS values in species with larger genomes for either species set. We also found little evidence for relaxation of selection in species with larger genomes. A positive correlation between genome size and range size (a proxy of population size) in this group disagrees with predictions of stronger drift in species with larger genomes. Our results highlight the complex interactions between the many forces shaping genomic variation in organisms with genomic gigantism.

Dataset on biodiversity and agronomic performance of lentil and chickpea field trials in the Mediterranean Region.

Pulse crops have become more important in food production and consumption systems for the transition towards sustainability. We present an agroecological dataset from 304 samples from 12 legume field trials in five locations across three countries in the Mediterranean. The field trials were established in the seasons 2021/22 and 2022/23 and tested different lentil or chickpea cultivars, inoculants, intercropping and weeding regimes. The dataset encompasses detailed information on wild flora diversity, grain yield, associated management practices, soil texture and weather during the growing period. Wild flora diversity was recorded by conducting a vegetation survey in 1 × 2 m sample plots. Grain yield was determined at the crop maturity stage, with full plots harvested in Spain, while samples were taken in Croatia and Tunisia. Environmental variables were via laboratory analysis or bottle testing of soil samples and analysis of local weather data. The comprehensiveness of the dataset, including all relevant agroecological information, enables other researchers to employ the dataset for various statistical analyses of agroecosystem processes, such as plant-environment interactions or biodiversity-yield trade-off analysis.

Comparison of available methods to evaluate cefiderocol susceptibility in Acinetobacter spp.

Recently, considerable uncertainty has arisen concerning the appropriate susceptibility testing for cefiderocol in gram-negative bacilli, particularly in the context of its application to Acinetobacter spp. The optimal method for assessing the susceptibility levels of Acinetobacter spp. to cefiderocol remains a subject of debate due to substantial disparities observed in the values obtained through various testing procedures. This study employed four minimum inhibitory concentration (MIC) methodologies and the disk diffusion to assess the susceptibility of twenty-seven carbapenem resistant (CR)-Acinetobacter strains to cefiderocol. The results from our study reveal significant variations in the minimum inhibitory concentration (MIC) values obtained with the different methods and in the level of agreement in interpretation categories between the different MIC methods and the disk diffusion test. Among the MIC methods, there was relatively more consistency in reporting the interpretation categories. For European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, the categorical agreement (CA) for MIC methods ranged between 66.7 and 81.5%. On the other hand, the essential agreement (EA) values were as low as 18.5-29.6%. The CA between MIC methods and disk diffusion was 81.5%. These results emphasize the need for a reliable, accurate, and clinically validated methodology to effectively assess the susceptibility of Acinetobacter spp. to cefiderocol. The wide variability observed in our study highlights the importance of standardizing the susceptibility testing process for cefiderocol to ensure consistent and reliable results for clinical decision-making.

Structure-activity relationship of pyrrolidine pentamine derivatives as inhibitors of the aminoglycoside 6'- N -acetyltransferase type Ib.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by aminoglycoside 6'- N -acetyltransferase type I enzyme, of which type Ib [AAC(6')-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive compounds to be developed as drugs. Mixture-based combinatorial libraries and positional scanning strategy led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1 - R5), inhibits AAC(6')-Ib-mediated inactivation of amikacin. Structure-activity relationship (SAR) studies showed that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003 , reduced inhibition levels, demonstrating the essential nature not only of the presence of an S -phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions have varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity. Highlights: Amikacin resistance in Gram-negatives is mostly caused by the AAC(6')-Ib enzymeAAC(6')-Ib has been identified in most Gram-negative pathogensInhibitors of AAC(6')-Ib could be used to treat resistant infectionsCombinatorial libraries and positional scanning identified an inhibitorThe lead compound can be optimized by structure activity relationship studies.

A Novel Approach for Dermal Application of Pranoprofen-Loaded Lipid Nanoparticles for the Treatment of Post-Tattoo Inflammatory Reactions.

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading pranoprofen (PRA-NLC) as a tattoo aftercare formulation to reduce the inflammation associated with tattooing. In this context, the in vitro drug release and the ex vivo permeation-through-human-skin tests using Franz cells were appraised. The tolerance of our formulation on the skin was evaluated by studying the skin's biomechanical properties. In addition, an in vivo anti-inflammatory study was conducted on mice skin to evaluate the efficacy of the formulation applied topically after tattooing the animals. PRA-NLC showed a sustained release up to 72 h, and the amount of pranoprofen retained in the skin was found to be 33.48 µg/g/cm2. The formulation proved to be well tolerated; it increased stratum corneum hydration, and no signs of skin irritation were observed. Furthermore, it was demonstrated to be non-cytotoxic since the cell viability was greater than 80%. Based on these results, we concluded that PRA-NLC represents a suitable drug delivery carrier for the transdermal delivery of pranoprofen to alleviate the local skin inflammation associated with tattooing.

EGFR-ERK1/2 signaling and mitochondrial dynamics in seasonal ovarian steroidogenesis of the muskrats (Ondatra zibethicus).

The dynamic systems of mitochondria, including mitochondrial fusion and fission, are essential for ovarian endocrine and follicular development. Meanwhile, ERK1/2 signaling is an important mechanism mediating altered mitochondrial dynamics and steroidogenesis. The purpose of this study was to investigate the seasonal changes in ovarian steroidogenesis concerning EGFR-ERK1/2 signaling and mitochondrial dynamics of the muskrats (Ondatra zibethicus). The results showed that follicular development in the muskrats remained in the tertiary follicular stage during the non-breeding season, accompanied by a significant decrease in serum and ovarian concentrations of 17ß-estradiol and progesterone from the breeding season to the non-breeding season. EGF, EGFR, ERK1/2, p-ERK1/2, and mitochondrial dynamics regulators were mainly localized in granulosa cells and theca cells of muskrats during the breeding and non-breeding seasons. The mRNA levels of Egfr, Erk1/2, Mfn1/2, Opa1, Drp1, and steroidogenic enzymes in the ovaries were remarkably higher during the breeding season. The 17ß-estradiol concentrations in the serum and ovaries as well as the relative levels of Mfn1/2, Opa1, and Drp1 were positively associated with each other. Furthermore, transcriptomic analysis of the ovaries revealed that differentially expressed genes might be linked to steroid biosynthesis, estrogen signaling pathway, and mitochondrial membrane-related pathways. In conclusion, these results suggest that the up-regulation of mitochondrial dynamics regulators during the breeding season is closely associated with enhanced ovarian steroidogenesis in the muskrats, which may be regulated by upstream EGFR-ERK1/2 signaling.

Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.

BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM.

ATTR amyloidosis is a degenerative disorder characterized by the systemic deposition of the protein transthyretin. These amyloid aggregates of transthyretin (ATTR) can deposit in different parts of the body causing diverse clinical manifestations. Our laboratory aims to investigate a potential relationship between the different genotypes, organ of deposition, clinical phenotypes, and the structure of ATTR fibrils. Using cryo-electron microscopy, we have recently described how the neuropathic related mutations ATTRv-I84S and ATTRv-V122∆ can drive structural polymorphism in ex vivo fibrils. Here we question whether the mutation ATTRv-T60A, that commonly triggers cardiac and neuropathic symptoms, has a similar effect. To address this question, we extracted and determined the structure of ATTR-T60A fibrils from multiple organs (heart, thyroid, kidney, and liver) from the same patient and from the heart of two additional patients. We have found a consistent conformation among all the fibril structures, acquiring the "closed-gate morphology" previously found in ATTRwt and others ATTRv related to cardiac or mixed manifestations. The closed-gate morphology is composed by two segments of the protein that interact together forming a polar channel, where the residues glycine 57 to isoleucine 68 act as a gate of the polar cavity. Our study indicates that ATTR-T60A fibrils present in peripheral organs adopt the same structural conformation in all patients, regardless of the organ of deposition.

S100 proteins: a new frontier in fibromyalgia research.

Fibromyalgia (FM) is a chronic condition that causes widespread pain, fatigue, and other symptoms that significantly affect quality of life. The underlying mechanisms of fibromyalgia involve both the immune system and the central nervous system. It has been proposed that changes in multiple ascending and descending pathways in the central nervous system may contribute to increased pain sensitivity in individuals with this condition. Recent research has identified S100 proteins as a new area of interest in fibromyalgia studies. These proteins are a group of small molecular weight proteins involved in inflammation and various functions inside and outside of cells, and they may play a critical role in the development and progression of FM. Although S100B has been the most studied in FM patients, other studies have reported that S100A7, S100A8, S100A9, and S100A12 may also be useful as potential biomarkers or for a deeper understanding of FM pathophysiology. The potential role of S100 proteins in the pathophysiology of fibromyalgia could be mediated by RAGE and TLR4, which signal through JNK, ERK, and p38 to activate AP-1 and NF-κB and induce the release of proinflammatory cytokines, thereby producing the inflammation, fatigue, and chronic pain characteristic of fibromyalgia. To gain new perspectives on targeted therapeutic approaches, it is crucial to understand how S100 proteins could impact the pathophysiology of fibromyalgia. This review examines the potential role of S100 proteins in fibromyalgia and their impact on improving our comprehension of the condition, as well as facilitating further research on this interesting topic.

ATTRv-V30M Type A amyloid fibrils from heart and nerves exhibit structural homogeneity.

ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin, a protein integral to transporting retinol and thyroid hormones. Transthyretin is primarily produced by the liver and circulates in blood as a tetramer. The retinal epithelium also secretes transthyretin, which is secreted to the vitreous humor of the eye. Because of mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering amyloid fibril formation. The deposition of transthyretin amyloid fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryo-electron microscopy, here we determined the structures of amyloid fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found that fibrils from both tissues share a consistent structural conformation, similar to the previously described structure of cardiac fibrils from an individual with the same genotype, but different from the fibril structure obtained from the vitreous humor. Our study hints to a uniform fibrillar architecture across different tissues within the same individual, only when the source of transthyretin is the liver. Moreover, this study provides the first description of ATTR fibrils from the nerves of a patient and enhances our understanding of the role of deposition site and protein production site in shaping the fibril structure in ATTRv-V30M amyloidosis.

Amyloid fibril polymorphism in the heart of an ATTR amyloidosis patient with polyneuropathy attributed to the V122Δ variant.

ATTR amyloidosis is a phenotypically heterogeneous disease characterized by the pathological deposition of transthyretin in the form of amyloid fibrils into various organs. ATTR amyloidosis may stem from mutations in variant (ATTRv) amyloidosis, or aging in wild-type (ATTRwt) amyloidosis. ATTRwt generally manifests as a cardiomyopathy phenotype, whereas ATTRv may present as polyneuropathy, cardiomyopathy, or mixed, in combination with many other symptoms deriving from secondary organ involvement. Over 130 different mutational variants of transthyretin have been identified, many of them being linked to specific disease symptoms. Yet, the role of these mutations in the differential disease manifestation remains elusive. Using cryo-electron microscopy, here we structurally characterized fibrils from the heart of an ATTRv patient carrying the V122Δ mutation, predominantly associated with polyneuropathy. Our results show that these fibrils are polymorphic, presenting as both single and double filaments. Our study alludes to a structural connection contributing to phenotypic variation in ATTR amyloidosis, as polymorphism in ATTR fibrils may manifest in patients with predominantly polyneuropathic phenotypes.

Morphological and Molecular Identification of Ulva spp. (Ulvophyceae; Chlorophyta) from Algarrobo Bay, Chile: Understanding the Composition of Green Tides.

Green algae blooms of the genus Ulva are occurring globally and are primarily attributed to anthropogenic factors. At Los Tubos beach in Algarrobo Bay along the central Chilean coast, there have been blooms of these algae that persist almost year-round over the past 20 years, leading to environmental, economic, and social issues that affect the local government and communities. The objective of this study was to characterize the species that form these green tides based on a combination of ecological, morpho-anatomical, and molecular information. For this purpose, seasonal surveys of beached algal fronds were conducted between 2021 and 2022. Subsequently, the sampled algae were analyzed morphologically and phylogenetically using the molecular markers ITS1 and tufA, allowing for the identification of at least five taxa. Of these five taxa, three (U. stenophylloides, U. uncialis, U. australis) have laminar, foliose, and distromatic morphology, while the other two (U. compressa, U. aragoensis) have tubular, filamentous, and monostromatic fronds. Intertidal surveys showed that U. stenophylloides showed the highest relative coverage throughout the seasons and all intertidal levels, followed by U. uncialis. Therefore, we can establish that the green tides on the coast of Algarrobo in Chile are multispecific, with differences in relative abundance during different seasons and across the intertidal zone, opening opportunities for diverse future studies, ranging from ecology to algal biotechnology.

Biodegradable Biocomposite of Starch Films Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Reinforced by Microfibrillated Cellulose.

Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.

Single-Center In-Hospital and Outpatient Opioid Use for Lower Extremity Arterial Disease.

INTRODUCTION: The pain associated with lower extremity arterial disease is difficult to treat, even with lower extremity revascularization. We sought to evaluate in-hospital and post-operative opioid usage in patients with different disease severities and treatments for lower extremity vascular disease. METHODS: A retrospective review was performed for all hospital encounters for patients with an International Classification of Diseases (ICD) code consistent with lower extremity arterial disease admitted to a single center between January 2018 and March 2023. Cases included patients admitted to the hospital with a primary diagnosis of lower extremity arterial disease. These patients were subdivided based on disease severity, treatment type, and comorbid diagnosis of diabetes mellitus. The analysis focused on in-hospital opioid use frequency and dosage among these patients. The control group (CON) included encounters for patients admitted with a secondary diagnosis of lower extremity atherosclerotic disease. A total of 438 patients represented by all the analyzed encounters were then reviewed for the number and type of vascular procedures performed as well as opioid use in the outpatient setting for one year. RESULTS: Critical limb ischemia (CLI) encounters were more likely to use opioids as compared to the CON and peripheral arterial disease (PAD) without rest pain, ulcer or gangrene groups (CLI 67.9% (95% CI: 63.6%-71.6%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.001 and CLI 67.9% (95% CI: 63.6%-71.6%) versus PAD 50.2% (95% CI: 42.6%-57.4%), p < 0.001). Opioid use was also more common in encounters for gangrene and groups treated with revascularization (REVASC) and amputation (AMP) as compared to CON (gangrene 74.5% (95% CI: 68.5%-82.1%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01; REVASC 58.3% (95% CI: 57.3%-66.4%) versus CON 52.1% (95% CI: 48.5%-55.7%), p =0.01; and AMP 72.3% (95% CI: 62.1%-74.0%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01). Significantly increased oral opioid doses per day (MME/day) were not noted for any of the investigated groups as compared to the CON. In the outpatient setting, 186 (42.5% (95% CI: 37.2%-46.4%)) patients were using opioids one month after the most recent vascular intervention. By one year, 31 (7.1% (95% CI: 1.30%-7.70%)) patients were still using opioids. No differences in opioid usage were noted for patients undergoing single versus multiple vascular interventions at one year. Patients undergoing certain vascular surgery procedures were more likely to be using opioids at one year. CONCLUSION: Patients with CLI and gangrene as well as those undergoing vascular treatment have a greater frequency of opioid use during hospital encounters as compared to those patients with less severe disease and undergoing conservative management, respectively. However, these findings do not equate to higher doses of opioids used during hospitalization. Patients undergoing multiple vascular procedures are not more likely to be using opioids long-term (at one year) as compared to those patients treated with single vascular procedures.

High-risk pregnancy and its relationship with the neurodevelopment and behavior of 2-year-old children.

High-risk pregnancies elevate maternal stress, impacting offspring neurodevelopment and behavior. This study, involving 112 participants, aimed to compare perceived stress, neurodevelopment, and behavior in high-risk and low-risk pregnancies. Two groups, high-risk and low-risk, were assessed during pregnancy for stress using hair cortisol and psychological analysis. At 24 months post-birth, their children's neurodevelopment and behavior were evaluated. Results revealed higher perceived stress and pregnancy-related concerns in high-risk pregnancies, contrasting with low-risk pregnancies. Offspring from high-risk pregnancies displayed elevated internalizing behavior scores, while low-risk pregnancies showed higher externalizing behavior scores. Additionally, women in low-risk pregnancies exhibited increased cortisol concentrations 24 months post-delivery. These findings underscore the necessity for early stress detection and prevention programs during pregnancy, particularly in high-risk cases, to enhance maternal and infant health.