Prospective validation of a preoperative scoring system for difficult laparoscopy cholecystectomy.

Difficult laparoscopic cholecystectomy (LC) is defined by its surgical outcomes, including operative time, conversion to open surgery, bile duct and/or vascular injury. Difficult LC can be graded based on intraoperative findings. The main objective of this study is to apply and validate the reliability of their proposed risk score to predict the operative difficulty of an LC, based on their own validated intraoperative scale. Single-center prospective cohort study from 01/2020-12-2023. 367 patients > 18 years who underwent LC were included. The preoperative risk scale and intraoperative grading system were registered. Surgical outcomes were determined. Predictive accuracy was evaluated by the Receiver Operator Characteristic curve, sensitivity, specificity, positive, and negative predictive values, and Youden's Index (J). Patients' mean age was 44.1 ± 15.3 years. According to the risk score, 39.5% LC were "low" risk difficulty, 49.3% were "medium" risk, and 11.2% were "high" risk difficult LC. Based on the intraoperative grading system, 31.9% were difficult LC (Nassar grades 3-4) and 68.1% were easy LC (Nassar grades 1-2). There was a statistically significant correlation (0.428, p < 0.05) between the preoperative risk score and the intraoperative grading system. The AUC for the preoperative risk score scale and intraoperative difficult LC was 0.735 (95% CI 0.687-0.779) (J: 0.34). A preoperative risk score > 1.5 had an 83.7% sensitivity and a 50.8% specificity for intraoperative difficult LC. A predictive preoperative score for difficult LC and a routine collection of the intraoperative difficulty should be implemented to improve surgical outcomes and surgical planning.

Neutrophil-to-lymphocyte ratio may predict complications and patency in bile duct injury repair.

BACKGROUND: Bile duct injury (BDI) repair surgery is usually associated with morbidity/mortality. The neutrophil-to-lymphocyte ratio (NLR) easily assesses a patient's inflammatory status. The study aims to determine the possible relationship between preoperative NLR (pNLR) with postoperative outcomes in BDI repair surgery. METHODS: Approved Ethics/Research Committee retrospective study, in patients who had a Bismuth-Strasberg type E BDI repair (2008-2023). Data registered was: morbidity, mortality, and long-term outcomes (primary patency and loss of primary patency) (Kaplan-Meier). Group comparison (U Mann-Whitney), receiver operator characteristic (ROC): area under curve [AUC]; cut-off value, and Youden index [J], and logistic regression analysis were used for pNLR evaluation. RESULTS: Seventy-three patients were studied. Mean age was 44.4 years. E2 was the commonest BDI (38.4%). Perioperative morbidity/mortality was 31.5% and 1.4%. Primary patency was 95.9%. 8.2% have lost primary patency (3-year actuarial patency: 85.3%). Median pNLR was higher in patients who had any complication (4.84 vs. 2.89 p = 0.015), biliary complications (5.29 vs. 2.86 p = 0.01), and patients with loss of primary patency (5.22 vs. 3.1 p = 0.08). AUC's, cut-off values and (J) were: any complication (0.678, pNLR = 4.3, J = 0.38, p = 0.007), serious complication (0.667, pNLR = 4.3, J = 0.34, p = 0.04), biliary complications (0.712, pNLR = 3.64, J = 0.46, p = 0.001), and loss of primary patency (0.716, pNLR = 3.24, J = 0.52, p = 0.008). Logistic regression was significant in any complication (Exp [B]: 0.1, p = 0.002), serious complications (Exp [B]: 0.2, p = 0.03), and biliary complications (Exp [B]: 8.1, p = 0.003). CONCLUSIONS: pNLR is associated with complications in BDI repair with moderate to acceptable predictive capacity. pNLR could potentially predict patency of a BDI repair.

Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES).

The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.

Sleep disturbances and incident risk of major depressive disorder in a population-based cohort.

Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years' follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022-1.103], p = 0.002 and 1.437 [1.064-1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064-1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463-0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort.

Screening blood donors for malaria, can we increase the number of eligible donors? An observational retrospective study.

BACKGROUND: In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. METHODS: An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015-2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. RESULTS: During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33-48); median time to consultation was 32 months (IQR:12.5-110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). CONCLUSIONS: None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

Automated facial recognition system using deep learning for pain assessment in adults with cerebral palsy.

Objective: Assessing pain in individuals with neurological conditions like cerebral palsy is challenging due to limited self-reporting and expression abilities. Current methods lack sensitivity and specificity, underlining the need for a reliable evaluation protocol. An automated facial recognition system could revolutionize pain assessment for such patients.The research focuses on two primary goals: developing a dataset of facial pain expressions for individuals with cerebral palsy and creating a deep learning-based automated system for pain assessment tailored to this group. Methods: The study trained ten neural networks using three pain image databases and a newly curated CP-PAIN Dataset of 109 images from cerebral palsy patients, classified by experts using the Facial Action Coding System. Results: The InceptionV3 model demonstrated promising results, achieving 62.67% accuracy and a 61.12% F1 score on the CP-PAIN dataset. Explainable AI techniques confirmed the consistency of crucial features for pain identification across models. Conclusion: The study underscores the potential of deep learning in developing reliable pain detection systems using facial recognition for individuals with communication impairments due to neurological conditions. A more extensive and diverse dataset could further enhance the models' sensitivity to subtle pain expressions in cerebral palsy patients and possibly extend to other complex neurological disorders. This research marks a significant step toward more empathetic and accurate pain management for vulnerable populations.

Immediate implant placement influenced by musical flow: a prospective randomized controlled clinical trial.

BACKGROUND: The purpose of this study was to test how musical flow using baroque (BM) and classical era music (CM) as a non-pharmacological therapy can control anxiety and pain levels among patients undergoing IPI (Immediate post-extraction implants). METHODS: 78 patients who required an IPI were enrolled in this randomized clinical trial. Each patient was assigned to one of the three experimental groups with a simple randomization: Group I (n = 26) listened to BM; Group II (n = 27) listened to CM; and Group III (n = 25) did not listen to music and was the control group (C). The physiological dependent variables analyzed were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and oxygen saturation (SpO2). The psychological dependent variable analyzed was modified dental anxiety scale (MDAS) and visual analogue scale (VAS), measured before and after surgery. In all cases, the level of statistical significance was set at p < 0.01. RESULTS: Statistically significant differences were found in the SBP decrease in the CM group (p = 0.001, CI = 1.9716-6.5840) and the BM group (p = 0.003, CI = 1.4450-6.4396). Anxiety levels during the intervention decreased in both groups that listened to music: BM group (p = 0.002, CI = 0.645-2.662) and CM group (p = 0.000, CI = 1.523-3.884). CONCLUSIONS: Patients undergoing IPI placement surgery can register lower levels of SBP when listening to BM and CM than patients who were not exposed to the musical flow, improving their anxiety levels.

Sex differences in the functional network underpinnings of psychotic-like experiences in children.

Psychotic-like experiences (PLEs) include a range of sub-threshold symptoms that resemble aspects of psychosis but do not necessarily indicate the presence of psychiatric illness. These experiences are highly prevalent in youth and are associated with developmental disruptions across social, academic, and emotional domains. While not all youth who report PLEs develop psychosis, many develop other psychiatric illnesses during adolescence and adulthood. As such, PLEs are theorized to represent early markers of poor mental health. Here, we characterized the similarities and differences in the neurobiological underpinnings of childhood PLEs across the sexes using a large sample from the ABCD Study (n=5,260), revealing sex-specific associations between functional networks connectivity and PLEs. We find that although the networks associated with PLEs overlap to some extent across the sexes, there are also crucial differences. In females, PLEs are associated with dispersed cortical and non-cortical connections, whereas in males, they are primarily associated with functional connections within limbic, temporal parietal, somato/motor, and visual networks. These results suggest that early transdiagnostic markers of psychopathology may be distinct across the sexes, further emphasizing the need to consider sex in psychiatric research as well as clinical practice.

Region specific anisotropy and rate dependence of Göttingen minipig brain tissue.

Traumatic brain injury is a major cause of morbidity in civilian as well as military populations. Computational simulations of injurious events are an important tool to understanding the biomechanics of brain injury and evaluating injury criteria and safety measures. However, these computational models are highly dependent on the material parameters used to represent the brain tissue. Reported material properties of tissue from the cerebrum and cerebellum remain poorly defined at high rates and with respect to anisotropy. In this work, brain tissue from the cerebrum and cerebellum of male Göttingen minipigs was tested in one of three directions relative to axon fibers in oscillatory simple shear over a large range of strain rates from 0.025 to 250 s-1. Brain tissue showed significant direction dependence in both regions, each with a single preferred loading direction. The tissue also showed strong rate dependence over the full range of rates considered. Transversely isotropic hyper-viscoelastic constitutive models were fit to experimental data using dynamic inverse finite element models to account for wave propagation observed at high strain rates. The fit constitutive models predicted the response in all directions well at rates below 100 s-1, after which they adequately predicted the initial two loading cycles, with the exception of the 250 s-1 rate, where models performed poorly. These constitutive models can be readily implemented in finite element packages and are suitable for simulation of both conventional and blast injury in porcine, especially Göttingen minipig, models.

Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland.

BACKGROUND: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term. METHODS: We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study. FINDINGS: We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis. INTERPRETATION: The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis. FUNDING: Northwell Health and Sigrid Jusèlius Foundation.

Shared EEG correlates between non-REM parasomnia experiences and dreams.

Sleepwalking and related parasomnias result from incomplete awakenings out of non-rapid eye movement sleep. Behavioral episodes can occur without consciousness or recollection, or in relation to dream-like experiences. To understand what accounts for these differences in consciousness and recall, here we recorded parasomnia episodes with high-density electroencephalography (EEG) and interviewed participants immediately afterward about their experiences. Compared to reports of no experience (19%), reports of conscious experience (56%) were preceded by high-amplitude EEG slow waves in anterior cortical regions and activation of posterior cortical regions, similar to previously described EEG correlates of dreaming. Recall of the content of the experience (56%), compared to no recall (25%), was associated with higher EEG activation in the right medial temporal region before movement onset. Our work suggests that the EEG correlates of parasomnia experiences are similar to those reported for dreams and may thus reflect core physiological processes involved in sleep consciousness.

Peak alpha frequency and electroencephalographic microstates are correlated with aggression in schizophrenia.

Large scale retrospective studies have shown an association between schizophrenia and risk of violence. Overall, this increase in risk is small and does not justify or support stigmatizing public perceptions or media depictions of people with schizophrenia. Nonetheless, in some situations, some symptoms of schizophrenia can increase the risk of violent behavior. Prediction of this behavior would allow high impact preventive interventions. However, to date the neurobiological correlates of violent behavior in schizophrenia are not well understood, precluding the development of prognostic biomarkers. We used electroencephalography to measure alpha activity and microstates from 31 patients with schizophrenia and 18 age matched controls. Participants also completed multiple assessments of current aggressive tendencies and their lifetime history of aggressive acts. We found that individual alpha peak frequency was negatively correlated with aggression scores in both patients and controls (largest Spearman's r = -0.45). Furthermore, this result could be replicated in data taken from a single frontal channel suggesting that this may be possible to obtain in routine clinical settings (largest Spearman's r = -0.40). We also found that transitions between microstates corresponding to auditory and visual networks were inversely correlated with aggression scores. Finally, we found that, within patients, aggression was correlated with the degree of randomness between microstate transitions. This suggests that aggression is related to inappropriate switching between large scale brain networks and subsequent failure to appropriately integrate complicated environmental and internal stimuli. By elucidating some of the electrophysiological correlates of aggression, these data facilitate the development of prognostic biomarkers.

NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.

Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 (NUDCD3). Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T -B- SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans.

Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank.

The human retina is part of the central nervous system and can be easily and non-invasively imaged with optical coherence tomography. While imaging the retina may provide insights on central nervous system-related disorders such as schizophrenia, a typical challenge are confounders often present in schizophrenia which may negatively impact retinal health. Here, we therefore aimed to investigate retinal changes in the context of common genetic variations conveying a risk of schizophrenia as measured by polygenic risk scores. We used population data from the UK Biobank, including White British and Irish individuals without diagnosed schizophrenia, and estimated a polygenic risk score for schizophrenia based on the newest genome-wide association study (PGC release 2022). We hypothesized that greater genetic susceptibility to schizophrenia is associated with retinal thinning, especially within the macula. To gain additional mechanistic insights, we conducted pathway-specific polygenic risk score associations analyses, focusing on gene pathways that are related to schizophrenia. Of 65484 individuals recruited, 48208 participants with available matching imaging-genetic data were included in the analysis of whom 22427 (53.48%) were female and 25781 (46.52%) were male. Our robust principal component regression results showed that polygenic risk scores for schizophrenia were associated with retinal thinning while controlling for confounding factors (b = -0.03, p = 0.007, pFWER = 0.01). Similarly, we found that polygenic risk for schizophrenia specific to neuroinflammation gene sets revealed significant associations with retinal thinning (b = -0.03, self-contained p = 0.041 (reflecting the level of association), competitive p = 0.05 (reflecting the level of enrichment)). These results go beyond previous studies suggesting a relationship between manifested schizophrenia and retinal phenotypes. They indicate that the retina is a mirror reflecting the genetic complexities of schizophrenia and that alterations observed in the retina of individuals with schizophrenia may be connected to an inherent genetic predisposition to neurodegenerative aspects of the condition. These associations also suggest the potential involvement of the neuroinflammatory pathway, with indications of genetic overlap with specific retinal phenotypes. The findings further indicate that this gene pathway in individuals with a high polygenic risk for schizophrenia could contribute through acute-phase proteins to structural changes in the retina.

Observer-based differential evolution constrained control for safe reference tracking in robots.

Big torque inputs in controls could increase energy consumption, and big estimated perturbations in observers could produce device damages. Therefore, it would be interesting to propose a constrained control for safe reference tracking and a constrained observer for safe perturbation estimation in robots. Furthermore, the best gains in controls produce a balance between safe reference tracking and save energy consumption. Therefore, it would be interesting to propose a method to find the best gains. In this paper, an observer-based differential evolution constrained control is proposed for safe reference tracking in robots. The contributions are described as follows: (1) a constrained observer is proposed for safe perturbation estimation in robots, (2) a constrained control is proposed for safe reference tracking in robots, (3) a differential evolution optimizer is used to find the best gains in an observer-based constrained control, (4) the robust stability in an observer-based constrained control is assured, (5) the pseudo-code of an observer-based differential evolution constrained control is detailed. The proposed observer-based differential evolution constrained control is applied for safe reference tracking in two robots.

Stability-based approaches in chemoproteomics.

Target deconvolution can help understand how compounds exert therapeutic effects and can accelerate drug discovery by helping optimise safety and efficacy, revealing mechanisms of action, anticipate off-target effects and identifying opportunities for therapeutic expansion. Chemoproteomics, a combination of chemical biology with mass spectrometry has transformed target deconvolution. This review discusses modification-free chemoproteomic approaches that leverage the change in protein thermodynamics induced by small molecule ligand binding. Unlike modification-based methods relying on enriching specific protein targets, these approaches offer proteome-wide evaluations, driven by advancements in mass spectrometry sensitivity, increasing proteome coverage and quantitation methods. Advances in methods based on denaturation/precipitation by thermal or chemical denaturation, or by protease degradation are evaluated, emphasising the evolving landscape of chemoproteomics and its potential impact on future drug-development strategies.

Edge Artificial Intelligence (AI) for real-time automatic quantification of filariasis in mobile microscopy.

Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood samples can detect and differentiate parasite species, but it is time consuming and requires expert microscopists, a resource that is not always available. In this context, artificial intelligence (AI) can assist in the diagnosis of this disease by automatically detecting and differentiating microfilariae. In line with the target product profile for lymphatic filariasis as defined by the World Health Organization, we developed an edge AI system running on a smartphone whose camera is aligned with the ocular of an optical microscope that detects and differentiates filarias species in real time without the internet connection. Our object detection algorithm that uses the Single-Shot Detection (SSD) MobileNet V2 detection model was developed with 115 cases, 85 cases with 1903 fields of view and 3342 labels for model training, and 30 cases with 484 fields of view and 873 labels for model validation before clinical validation, is able to detect microfilariae at 10x magnification and distinguishes four species of them at 40x magnification: Loa loa, Mansonella perstans, Wuchereria bancrofti, and Brugia malayi. We validated our augmented microscopy system in the clinical environment by replicating the diagnostic workflow encompassed examinations at 10x and 40x with the assistance of the AI models analyzing 18 samples with the AI running on a middle range smartphone. It achieved an overall precision of 94.14%, recall of 91.90% and F1 score of 93.01% for the screening algorithm and 95.46%, 97.81% and 96.62% for the species differentiation algorithm respectively. This innovative solution has the potential to support filariasis diagnosis and monitoring, particularly in resource-limited settings where access to expert technicians and laboratory equipment is scarce.

Proteomic Analysis Reveals Trilaciclib-Induced Senescence.

Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in hematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in hematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukemia cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukemia, acute lymphoblastic leukemia, and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilizing cyclin-dependent kinase 4/6 and downregulating cell cycle-related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the nonsmall cell lung carcinoma cell line, A549. These findings highlight trilaciclib's potential as a therapeutic option for hematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in chronic myeloid leukemia treatment, as well as in nonsmall cell lung carcinoma cell line.

Cornual adenomyosis in Essure® device users and in patients hysterectomized for other causes: A retrospective cohort study.

OBJECTIVE: To determine whether adenomyosis is present in the cornual portion of hysterectomies of symptomatic sterilization device users and in patients hysterectomized for different benign causes and who presented with pelvic pain and/or menstrual alterations. METHODS: An observational, analytical, cross-sectional, single-center, retrospective cohort study was conducted in a secondary level hospital. Cohort 1 consisted of women who had Essure® hysteroscopic sterilization devices inserted between 2009 and 2017, who developed gynecologic symptoms (pelvic pain, heavy menstrual bleeding, and/or abnormal uterine bleeding) and who underwent a hysterectomy for explantation of the devices. Cohort 2 consisted of women with the same gynecologic symptoms, who underwent a hysterectomy for other benign causes. All surgeries were performed by the gynecology team between 2018 and 2022. A descriptive and comparative analysis of sociodemographic, clinical characteristics, and pathologic findings between cohorts was made. RESULTS: In total, 96 patients were studied (cohort 1 included 34 women, cohort 2 included 62 women). Pelvic pain was found to be more frequent in the cohort of Essure users (76.47% vs. 50%, P = 0.012), with a ratio of three times higher in this group (odds ratio 3.25, 95% confidence interval 1.27-8.28). Adenomyosis was more frequently found in the Essure group, both at corporal and cornual portions, the latter being five times higher in this cohort (relative risk = 5.47; 95% confidence interval 1.17-25.64). CONCLUSIONS: The present study may be the first to describe cornual adenomyosis related to Essure devices. These devices may play a role in the development of adenomyosis and, consequently, pelvic pain. However, causality is difficult to establish.

Monosaccharide Analysis After One-Pot Derivatization Followed by Reverse-Phase Liquid Chromatography Separation and UV/Vis Detection.

Derivatization of monosaccharides with 1-phenyl-3-methyl-5-pyrazolone (PMP) introduces two chromophores per sugar molecule. Their separation on a superficially porous C18 reverse-phase column, using common liquid chromatography equipment, results in short analysis times (under 20 min) and high sensitivity (limit of quantitation 1 nmol). This method allows for complex monosaccharide mixtures to be separated and quantified using a reasonably simple and safe derivatization procedure.