Multifractal Heart Rate Value Analysis: A Novel Approach for Diabetic Neuropathy Diagnosis.

Type 2 diabetes mellitus (T2DM) is characterized by several complications, such as retinopathy, renal failure, cardiovascular disease, and diabetic neuropathy. Among these, neuropathy is the most severe complication, due to the challenging nature of its early detection. The linear Hearth Rate Variability (HRV) analysis is the most common diagnosis technique for diabetic neuropathy, and it is characterized by the determination of the sympathetic-parasympathetic balance on the peripheral nerves through a linear analysis of the tachogram obtained using photoplethysmography. We aimed to perform a multifractal analysis to identify autonomic neuropathy, which was not yet manifest and not detectable with the linear HRV analysis. We enrolled 10 healthy controls, 10 T2DM-diagnosed patients with not-full-blown neuropathy, and 10 T2DM diagnosed patients with full-blown neuropathy. The tachograms for the HRV analysis were obtained using finger photoplethysmography and a linear and/or multifractal analysis was performed. Our preliminary results showed that the linear analysis could effectively differentiate between healthy patients and T2DM patients with full-blown neuropathy; nevertheless, no differences were revealed comparing the full-blown to not-full-blown neuropathic diabetic patients. Conversely, the multifractal HRV analysis was effective for discriminating between full-blown and not-full-blown neuropathic T2DM patients. The multifractal analysis can represent a powerful strategy to determine neuropathic onset, even without clinical diagnostic evidence.

Comprehensive ethological analysis of fear expression in rats using DeepLabCut and SimBA machine learning model.

Introduction: Defensive responses to threat-associated cues are commonly evaluated using conditioned freezing or suppression of operant responding. However, rats display a broad range of behaviors and shift their defensive behaviors based on immediacy of threats and context. This study aimed to systematically quantify the defensive behaviors that are triggered in response to threat-associated cues and assess whether they can accurately be identified using DeepLabCut in conjunction with SimBA. Methods: We evaluated behavioral responses to fear using the auditory fear conditioning paradigm. Observable behaviors triggered by threat-associated cues were manually scored using Ethovision XT. Subsequently, we investigated the effects of diazepam (0, 0.3, or 1 mg/kg), administered intraperitoneally before fear memory testing, to assess its anxiolytic impact on these behaviors. We then developed a DeepLabCut + SimBA workflow for ethological analysis employing a series of machine learning models. The accuracy of behavior classifications generated by this pipeline was evaluated by comparing its output scores to the manually annotated scores. Results: Our findings show that, besides conditioned suppression and freezing, rats exhibit heightened risk assessment behaviors, including sniffing, rearing, free-air whisking, and head scanning. We observed that diazepam dose-dependently mitigates these risk-assessment behaviors in both sexes, suggesting a good predictive validity of our readouts. With adequate amount of training data (approximately > 30,000 frames containing such behavior), DeepLabCut + SimBA workflow yields high accuracy with a reasonable transferability to classify well-represented behaviors in a different experimental condition. We also found that maintaining the same condition between training and evaluation data sets is recommended while developing DeepLabCut + SimBA workflow to achieve the highest accuracy. Discussion: Our findings suggest that an ethological analysis can be used to assess fear learning. With the application of DeepLabCut and SimBA, this approach provides an alternative method to decode ongoing defensive behaviors in both male and female rats for further investigation of fear-related neurobiological underpinnings.

Different mechanisms underlie compulsive alcohol self-administration in male and female rats.

BACKGROUND: Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences ("compulsive use"). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors. METHODS: Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study. RESULTS: Unpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle. CONCLUSIONS: Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.

Sex plays an important role in the progression and treatment of alcohol addiction. While men show a higher prevalence of alcohol addiction, women are more susceptible to the adverse effects of excessive alcohol consumption. Additionally, women often rely on heavy drinking as a maladaptive coping mechanism to alleviate stress and anxiety, driven by negative affect. On the other hand, men are more likely to report heavy drinking and relapse in response to positive emotions and social influences. These sex-based differences underline the importance of understanding how vulnerability to alcohol addiction and its treatment varies in males and females.We used genetically heterogeneous rats to explore the behavioral traits that contribute to compulsivity, a key clinical feature of alcohol addiction. We found that motivation to self-administer alcohol was higher in males, while females showed higher compulsive alcohol self-administration. In males, motivation to self-administer alcohol showed a significant correlation with compulsivity, while in females compulsivity was predicted by higher basal corticosterone levels.These findings underlie the importance of sex-specific factors in compulsive alcohol self-administration, with potential prevention and treatment implications in alcohol addiction.

The "great imitator": IgG4-related disease of the oral cavity. Two case reports and scoping review.

This study aimed to review the lesser-known intraoral manifestations of immunoglobulin G4-related disease (IgG4-RD). In this paper we report an unprecedented case of oral IgG4-RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4-RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow-up duration. Fifty-one cases of oral IgG4-RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4-RD should report clear adherence to the recognized international diagnostic criteria of the disease.

Transcatheter Aortic Valve Implantation (TAVI) Planning with Dual-Layer Spectral CT Using Virtual Monoenergetic Image (VMI) Reconstructions and 20 mL of Contrast Media.

Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical implantation and its implementation is progressively increasing worldwide. We routinely perform pre-procedural aortic angiography CT to assess aortic dimensions and vascular anatomy. This study aims to evaluate the image quality of CTA for TAVI planning using dual-layer spectral CT, with virtual monoenergetic image reconstructions at 40 keV. Thirty-one patients underwent a CTA protocol with the injection of 20 mL of contrast media. Image quality was assessed by measuring the mean density in Hounsfield Units (HU), the signal-to-noise ratio, and the contrast-to-noise ratio in VMI reconstructions. Additionally, a blinded subjective analysis was conducted by two observers. The results showed significant enhancement at all sampled vascular levels with a gradual decrease in HU from proximal to distal regions. Favourable subjective ratings were given for all parameters, with greater variability in the evaluation of iliac axes. A significant negative correlation (p < 0.05) was observed between BMI and CA at all vascular levels, indicating reduced contrast enhancement with increasing BMI. Spectral CT, along with reducing iodine load, allows for obtaining high-quality images without a significant increase in noise. The reduction in iodine load can have positive implications in clinical practice, improving patient safety and resource efficiency.

Combined antiviral therapy as effective and feasible option in allogenic hematopoietic stem cell transplantation during SARS-COV-2 infection: a case report.

Here we describe the case of a 51 years old Italian woman with acute lymphoblastic leukemia who underwent to hematopoietic stem cell transplantation (HSCT) during SARS-COV-2 infection. She presented a prolonged COVID-19 successfully treated with dual anti SARS-COV-2 antiviral plus monoclonal antibody therapy.

A Multicenter International Retrospective Investigation Assessing the Prognostic Role of Inflammation-Based Scores (Neutrophil-to-Lymphocyte, Lymphocyte-to-Monocyte, and Platelet-to-Lymphocyte Ratios) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations of the Liver.

BACKGROUND: The utilization of inflammation-based scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR), has garnered attention for their potential as prognostic indicators in various cancers. However, their predictive role in patients with intermediate-stage HCC undergoing transcatheter arterial chemoembolization (TACE) remains an area that requires further investigation, as early recognition of TACE refractoriness holds the potential to guide tailored therapeutic interventions. METHODS: This multicenter international retrospective study analyzed data from patients with intermediate-stage HCC undergoing TACE between 2018 and 2024. Inflammation-based scores (NLR, LMR, PLR) were assessed preoperatively to predict treatment outcomes. RESULTS: Two hundred and fourteen patients were enrolled. Preoperative LMR showed the largest area under the curve for the prediction of 6-months PFS, based on the ROC curve analysis. Both high LMR (≥2.24) and low NLR (<4.72) were associated with improved objective response rates and 6-month progression-free survival. Lymphocyte count emerged as a strong predictor of treatment response in both simple (p < 0.001) and multiple (p < 0.001) logistic regression analyses. CONCLUSIONS: This study highlights the prognostic value of inflammation-based scores, particularly LMR and NLR, in predicting the treatment response and short-term outcomes of patients with intermediate-stage HCC undergoing TACE. Future investigations should focus on validating these scores' clinical applicability and assessing their impact on long-term patient survival and therapeutic decision-making.

Dual-Energy Computed Tomography in Urological Diseases: A Narrative Review.

Dual-Energy computed tomography (DECT) with its various advanced techniques, including Virtual Non-Contrast (VNC), effective atomic number (Z-eff) calculation, Z-maps, Iodine Density Index (IDI), and so on, holds great promise in the diagnosis and management of urogenital tumours. In this narrative review, we analyze the current status of knowledge of this technology to provide better lesion characterization, improve the staging accuracy, and give more precise treatment response assessments in relation to urological tumours.

Prognostic Role of Lymphocyte-to-Monocyte Ratio (LMR) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (DEM-TACE or cTACE) of the Liver: Exploring the Link between Tumor Microenvironment and Interventional Radiology.

Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, providing insights into tumor biology and facilitating personalized therapeutic interventions. This study addresses a dearth of recent literature exploring the prognostic significance of the preoperative LMR in individuals from western countries diagnosed with stage B hepatocellular carcinoma (HCC) undergoing drug eluting microspheres TACE (DEM-TACE) or conventional TACE (cTACE). This international multi-center retrospective analysis included consecutive patients with stage B HCC who underwent TACE from January 2017 to June 2023. The study evaluated the ability of the preoperative LMR to predict complete response (CR), objective response (OR), sustained response duration (SRD) exceeding 6 months, successful downstaging at 6 months, progression-free survival (PFS) at 6 months, and overall survival (OS) at 6 months. The study population included 109 HCC patients and it was divided into low LMR (LMR < 2.24) and high LMR (LMR ≥ 2.24) groups, according to ROC curve analysis to select the optimal LMR cut-off value. High LMR was associated with lower Hepatitis C prevalence, higher absolute lymphocyte count, and a trend toward lower alpha-fetoprotein. The group with high LMRs exhibited superior CR rates (14.9% vs. 0%), overall OR (43.2% vs. 14.3%), and better PFS at 6 months (75.7% vs. 45.7%). The LMR, specifically categorized as <2.24 and ≥2.24, emerged as a robust predictor for treatment response and short-term outcomes in patients with stage B HCC undergoing DEM- or c-TACE.

Innovative Experimental Ultrasound and US-Related Techniques Using the Murine Model in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a cancer with one of the highest mortality rates in the world. Several studies have been conductedusing preclinical experiments in mice to find new therapeutic strategies. Experimental ultrasound, in expert hands, is a safe, multifaceted, and relatively not-expensive device that helps researchers in several ways. In this systematic review, we propose a summary of the applications of ultrasonography in a preclinical mouse model of PDAC. Eighty-eight studies met our inclusion criteria. The included studies could be divided into seven main topics: ultrasound in pancreatic cancer diagnosis and progression (n: 21); dynamic contrast-enhanced ultrasound (DCE-US) (n: 5); microbubble ultra-sound-mediated drug delivery; focused ultrasound (n: 23); sonodynamic therapy (SDT) (n: 7); harmonic motion elastography (HME) and shear wave elastography (SWE) (n: 6); ultrasound-guided procedures (n: 9). In six cases, the articles fit into two or more sections. In conclusion, ultrasound can be a really useful, eclectic, and ductile tool in different diagnostic areas, not only regarding diagnosis but also in therapy, pharmacological and interventional treatment, and follow-up. All these multiple possibilities of use certainly represent a good starting point for the effective and wide use of murine ultrasonography in the study and comprehensive evaluation of pancreatic cancer.