The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice.

Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid ß-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.

Effect of Barley and Oat Consumption on Immune System, Inflammation and Gut Microbiota: A Systematic Review of Randomized Controlled Trials.

PURPOSE OF REVIEW: The aim of this systematic review was to investigate the effects of whole grain Avena sativa and Hordeum vulgare L., or their isolated fractions, on immune and inflammatory functions, as well as their influence on gut microbiota. A structured literature search was undertaken in line with PRISMA guidelines. Randomized controlled trials (RCTs) that investigated the effects of oats or barley consumption in adults and reported ≥ 1 of the following: C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-2, IL-8, IL-18, lipopolysacharide binding protein (LBP) or gut microbiota-related outcomes, were included. RECENT FINDINGS: A total of 16 RCTs were included, among which 6 studies recruited metabolically at-risk population, including individuals with overweight and obesity, metabolic syndrome or hypercholesterolemia. Additionally, 3 trials involved young healthy population, 5 trials targeted older individuals (aged over 50 years), and 2 studies encompassed populations with other disease states. A total of 1091 individuals were included in the evaluation of short-term (up to 14 days) and long-term (beyond 14 days, up to 90 days) supplementation with oats or barley-based products. 9 studies measured inflammatory biomarkers and 5 of them reported significant reductions, specifically in long-term studies. Notably, no evidence of anti-inflammatory benefits was found in healthy individuals, whereas studies involving metabolically at-risk populations showed promising reductions in inflammation. 13 studies measured the impact on gut microbiota, and collectively suggest that oats and barley food products can influence the composition of gut microbiota, associated in some cases with metabolic improvements. Oats and barley consumption may confer anti-inflammatory effects in metabolically at-risk populations and influence gut microbiota outcomes. However, no anti-inflammatory benefits were observed in healthy individuals. Results from this systematic review suggests caution in interpreting findings due to limited trials and variations in interventions and health conditions.

Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Circuital modelling in muscle tissue impedance measurements.

Electrical impedance spectroscopy (EIS) stands as a widely employed characterization technique for studying muscular tissue in both physio/pathological conditions. This methodology commonly involves modeling tissues through equivalent electrical circuits, facilitating a correlation between electrical parameters and physiological properties. Within existing literature, diverse equivalent electrical circuits have been proposed, varying in complexity and fitting properties. However, to date, none have definitively proven to be the most suiTable for tissue impedance measurements. This study aims to outline a systematic methodology for EIS measurements and to compare the performances of three widely used electrical circuits in characterizing both physiological and pathological muscle tissue conditions. Results highlight that, for optimal fitting with electrical parameters relevant to tissue characterization, the choice of the circuit to be fitted closely hinges on the specific measurement objectives, including measurement parameters and associated physiological features. Naturally, this necessitates a balance between simplicity and fitting accuracy.

Small microplastic ingestion by the calanoid Centropages furcatus in the Gulf of Thailand.

Microplastics could be ingested by many organisms, including zooplankton, involving bioaccumulation and biomagnification mechanisms a cross food webs. The information about microplastic ingestion by zooplankton keeps increasing worldwide. However, it is still limited for particle sizes under 300 µm (small microplastics, SMPs) and in areas such as Southeast Asia, which is considered one of the hotspots for plastic debris. This study aimed to characterize the size, shape, and polymer types of the SMPs ingested by the copepod Centropages furcatus in Si Chang Island (upper Gulf of Thailand). The study spans offshore and coastal waters, with data collected across wet, intermediate, and dry seasons. Using a semi-automated technique for micro-FTIR (Fourier-transform infrared) scanning spectroscopy for particle analysis, we found ingested SMPs in all samples. A total of 750 individuals of the calanoid Centropages furcatus were analyzed, finding 309 plastic particles and an average ingestion value of 0.41 ± 0.13 particles ind-1, one of the highest recorded values. All the particles were fragments, with a predominant size under 50 µm, and polymer types as Polypropylene (PP, 71 %), followed by Ethylene-Propylene-Diene-Monomer (EPDM, 16 %) and Polyethylene (PE, 7 %). Up to 470.2 particles m-3 were estimated to be retained by this calanoid species and potentially available for trophic transfer. The effect of rainfall on SMPs ingestion was inconclusive, with a non-significant observed tendency to higher ingestion values near the coastal area than offshore area, suggesting a decrease in particle exposure due to the runoff effect. Nevertheless, future studies should increase the frequency of surveys to arrive at better conclusions.

Age and sex mediated effects of estrogen and Β3-adrenergic receptor on cardiovascular pathophysiology.

Sex differences are consistently identified in determining the prevalence, manifestation, and response to therapies in several systemic disorders, including those affecting the cardiovascular (CV), skeletal muscle, and nervous system. Interestingly, such differences are often more noticeable as we age. For example, premenopausal women experience a lower risk of CV disease than men of the same age. While at an advanced age, with menopause, the risk of cardiovascular diseases and adverse outcomes increases exponentially in women, exceeding that of men. However, this effect appears to be reversed in diseases such as pulmonary hypertension, where women are up to seven times more likely than men to develop an idiopathic form of the disease with symptoms developing ten years earlier than their male counterparts. Explaining this is a complex question. However, several factors and mechanisms have been identified in recent decades, including a role for sex hormones, particularly estrogens and their related receptors. Furthermore, an emerging role in these sex differences has also been suggested for ß-adrenergic receptors (ßARs), which are essential regulators of mammalian physiology. It has in fact been shown that ßARs interact with estrogen receptors (ER), providing further demonstration of their involvement in determining sexual differences. Based on these premises, this review article focused on the ß3AR subtype, which shows important activities in adipose tissue but with new and interesting roles in regulating the function of cardiomyocytes and vascular cells. In detail, we examined how ß3AR and ER signaling are intertwined and whether there would be sex- and age-dependent specific effects of these receptor systems.

The Role of Double Interatrial Septum in Cryptogenic Stroke.

In this work, the case of a 70-year-old Caucasian woman affected by cryptogenic stroke is reported. After discarding other sources of embolism, a transesophageal echocardiogram was performed, which revealed the presence of a double interatrial septum associated with a left-sided atrial pouch. The persistent interatrial space was identified as the most probable source of thrombus.

Influence of monsoon seasonality and tidal cycle on microplastics presence and distribution in the Upper Gulf of Thailand.

Southeast Asian countries are recognized as significant contributors to the discharge of abundant plastic waste into the ocean. In this study, we conducted neuston net surveys on Si Chang Island of the Gulf of Thailand, a coral reef conservation area, to determine the presence of microplastic (MP) pollution. The survey, conducted during the wet (southwesterly monsoon), transition, and dry seasons (northeasterly monsoon), revealed that the MP abundance was in the range of 0.02-42.46 particles m-3. The precipitation, wind, and current direction induced by monsoons influenced the abundance and distribution of MP, presenting a significant seasonality. The cluster analysis for colors and polymer types of MPs suggested that the origin of plastic particles is diverse. Based on our results, a proposal for the generation, sources, and pathways for MPs in the Gulf of Thailand is presented: 1) plastic wastes exposed to strong UV light during the dry season get fragmented around the river, and 2) heavy rains wash away the particles during the wet season. This proposal is applicable to tropical regions, including the Gulf of Thailand. Therefore, this paper concluded that ocean currents induced by monsoons and the unique climate, resulting in the generation of MPs on land, increase MP presence and distribution in the ocean surrounding Southeast Asia countries. Furthermore, coral reef ecosystems can be particularly threatened by MPs in these areas. So, an increase in MP monitoring on coral ecosystems from Thailand and the world is highly recommended.

Adherence to the Mediterranean diet and depressive, anxiety, and stress symptoms in Spanish adolescents: results from the EHDLA study.

Depression and anxiety are prevalent and disabling conditions among adolescents. The aim of this study was to examine the relationship between adherence to the Mediterranean diet (MD) and depressive, anxiety, and stress symptoms in adolescents. This cross-sectional study included a sample of 698 adolescent students from a region of Spain (mean age of 13.9 ± 1.5 years; 56.2% girls). Adherence to the MD was evaluated with the Mediterranean Diet Quality Index in children and adolescents (KIDMED). Mental health symptoms were measured with the Depression, Anxiety, and Stress Scale (DASS-21). Logistic regression models were performed, including a wide range of potential confounders. Compared to individuals with low adherence to the MD, those with moderate and high adherence had lower odds of experiencing depressive symptoms (odds ratio [OR] = 0.40, 95% confidence interval [CI] 0.24-0.65 and OR = 0.33, 95% CI 0.20-0.55, respectively), which were statistically significant even after adjustment. No significant associations were found regarding anxiety or stress symptoms. Therefore, according to our results, higher adherence to the MD is inversely related to having depressive symptoms among adolescents, regardless of socioeconomic, anthropometric, and lifestyle factors. Considering the deleterious effects of mental health problems in youths, further research on the role of nonpharmacological strategies for the prevention and treatment of depressive symptoms in adolescence is essential.

High Cardiac Troponin Levels in Infants with Acute SARS-CoV-2 Infection: A Prospective Comparative Study.

OBJECTIVE: To investigate the specific role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in inducing elevation of marker of myocardial injury in infants with acute coronavirus disease 2019 (COVID-19). STUDY DESIGN: A prospective, multicentric 3-arm comparative study (March 2020 through March 2022) enrolling 152 infants hospitalized for COVID-19, 79 children with acute infections other than SARS-CoV-2, and 71 healthy controls. Determination of high-sensitivity cardiac troponin (hs-cTn) levels was the primary outcome. RESULTS: The proportion of children with hs-cTn values above the upper limit of normal (44 [28.9%]), as well as with a 3-fold increased value (20 [13.2%]) were significantly higher in the COVID-19 group than those in both control groups. The risk of presenting a 3-fold increased hs-cTn value was higher in children with SARS-CoV-2 infection compared with either healthy children (OR, 5.23; 95% CI, 1.19-23.02) or those with other infections (OR, 11.89; 95% CI, 1.56-89.79). In children with COVID-19, hs-cTn elevation was associated with neither clinical nor biochemical characteristics, nor perinatal risk factors, but with an age of <3 months (P < .001). After adjustment for age, sex, and underlying clinical conditions, elevated hs-cTn was independently associated with COVID-19 in a multivariable regression model. All children showed a progressive reduction of hs-cTn until normalization over time, without clinical, ECG, or echocardiographic manifestations up to 1 year of follow-up. CONCLUSIONS: Infants with acute SARS-CoV-2 infection may show a subclinical and transient alteration of myocardial injury markers, especially in the first months of life. hs-cTn levels normalized during follow-up and were not associated with cardiac functional impairment; nevertheless, long-term consequences are unknown and should be followed carefully.

[Somatometric alterations and lower APGAR score in indigenous newborns]. / Alteraciones somatométricas y menor puntaje APGAR en recién nacidos indígenas.

INTRODUCTION: the indigenous population is vulnerable and there is limited understanding of their somatometric indicators and APGAR score at birth. AIM: the objective of the study was to explore the association of the condition of indigenous newborn (INB) on somatometric parameters and APGAR score at birth. METHODS: this study employed an exploratory cross-sectional design, utilizing the registry of newborns (NB) from a private clinic. The APGAR score at one minute after birth, as well as nutritional indicators derived from measurements of weight, height, and perimeters, were taken into consideration. The statistical analysis involved the use of logistic regressions. RESULTS: the analysis included 7413 NB (1.8 % INB), 52 % were male and 8.1 % were born preterm (gestational age < 37 weeks). In comparison to non-indigenous NB, the INB group showed a higher risk of malnutrition (8 % vs. 6.3 %; p < 0.001), a greater prevalence of excess weight (7.3 % vs. 1.8 %; p < 0.001), smaller head circumference (33.6 cm vs. 34.1 cm; p = 0.017), smaller abdominal circumference (30.9 cm vs. 31.5 cm; p = 0.011), and a higher occurrence of low APGAR scores (< 7) (8.7 % vs. 1.2 %; p < 0.001). Furthermore, the indigenous condition was independently associated with low birth weight (< 2.500 g) (OR, 0.4; 95 % CI, 0.2; 0.9), excess head circumference (OR, 2.7; 95 % CI, 1.5; 4.7), and APGAR score < 7 points (OR, 8.3; 95 % CI, 4.2; 16.5). CONCLUSIONS: the indigenous condition was associated with factors that have adverse effects on the health of NB, including reduced head circumference and suboptimal performance on the APGAR scale. These results emphasize the importance of improving access to and quality of prenatal healthcare services for indigenous communities.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Development of soft tissue asymmetry indicators to characterize aging and functional mobility.

Introduction: The aging population poses significant challenges to healthcare systems globally, necessitating a comprehensive understanding of age-related changes affecting physical function. Age-related functional decline highlights the urgency of understanding how tissue composition changes impact mobility, independence, and quality of life in older adults. Previous research has emphasized the influence of muscle quality, but the role of tissue composition asymmetry across various tissue types remains understudied. This work develops asymmetry indicators based on muscle, connective and fat tissue extracted from cross-sectional CT scans, and shows their interplay with BMI and lower extremity function among community-dwelling older adults. Methods: We used data from 3157 older adults from 71 to 98 years of age (mean: 80.06). Tissue composition asymmetry was defined by the differences between the right and left sides using CT scans and the non-Linear Trimodal Regression Analysis (NTRA) parameters. Functional mobility was measured through a 6-meter gait (Normal-GAIT and Fast-GAIT) and the Timed Up and Go (TUG) performance test. Statistical analysis included paired t-tests, polynomial fitting curves, and regression analysis to uncover relationships between tissue asymmetry, age, and functional mobility. Results: Findings revealed an increase in tissue composition asymmetry with age. Notably, muscle and connective tissue width asymmetry showed significant variation across age groups. BMI classifications and gait tasks also influenced tissue asymmetry. The Fast-GAIT task demonstrated a substantial separation in tissue asymmetry between normal and slow groups, whereas the Normal-GAIT and the TUG task did not exhibit such distinction. Muscle quality, as reflected by asymmetry indicators, appears crucial in understanding age-related changes in muscle function, while fat and connective tissue play roles in body composition and mobility. Discussion: Our study emphasizes the importance of tissue asymmetry indicators in understanding how muscle function changes with age in older individuals, demonstrating their role as risk factor and their potential employment in clinical assessment. We also identified the influence of fat and connective tissue on body composition and functional mobility. Incorporating the NTRA technology into clinical evaluations could enable personalized interventions for older adults, promoting healthier aging and maintaining physical function.

Intranasal administration of molecular-gated mesoporous nanoparticles to increase ponatinib delivery to the brain.

Background: Glioblastoma is the most common and lethal brain cancer. New treatments are needed. However, the presence of the blood-brain barrier is limiting the development of new treatments directed toward the brain, as it restricts the access and distribution of drugs to the CNS. Materials & methods: In this work, two different nanoparticles (i.e., mesoporous silica nanoparticles and magnetic mesoporous silica nanoparticles) loaded with ponatinib were prepared. Results & conclusion: Both particles were characterized and tested in vitro and in vivo, proving that they are not toxic for blood-brain barrier cells and they increase the amount of drug reaching the brain when administered intranasally in comparison with the results obtained for the free drug.

This article presents a couple of promising nanoparticles for the treatment of brain cancer. This research is interesting because the brain and spinal cord are protected by a membrane that prevents toxic substances from reaching them but also hinders the access of drugs. One type of particle has a magnet in its core, so it can be driven with another external magnet until it reaches target; the other type does not have a magnet but has a small size, which would allow it to cross the membrane mentioned above. These particles have been proven to be able to kill cancer cells and to reach the brain after been administered through the nose in a better way than the free drug.

Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration.

Axolotl limb regeneration is accompanied by the transient induction of cellular senescence within the blastema, the structure that nucleates regeneration. The precise role of this blastemal senescent cell (bSC) population, however, remains unknown. Here, through a combination of gain- and loss-of-function assays, we elucidate the functions and molecular features of cellular senescence in vivo. We demonstrate that cellular senescence plays a positive role during axolotl regeneration by creating a pro-proliferative niche that supports progenitor cell expansion and blastema outgrowth. Senescent cells impact their microenvironment via Wnt pathway modulation. Further, we identify a link between Wnt signaling and senescence induction and propose that bSC-derived Wnt signals facilitate the proliferation of neighboring cells in part by preventing their induction into senescence. This work defines the roles of cellular senescence in the regeneration of complex structures.

Culture and the assumptions about appearance and reality: a scientometric look at a century of research.

Introduction: People represent the world in terms of two constructs: how something appears on the surface (appearance) and what it is underneath that surface (reality). Both constructs are central to various bodies of literature. What has not been done, however, is a systematic look at this collection of literature for overarching themes. Motivated by this research gap, the present scientometric review aimed to identify the common themes that penetrate through a century of scholarly work on appearance and reality. In doing so, this review also sketched a scientometric outline of the international network, pinpointing where the work was carried out. Methods: With CiteSpace software, we computed an optimized document co-citation analysis with a sample of 4,771 documents (1929-2022), resulting in a network of 1,785 nodes. Results and discussion: We identified impactful publications, summarized major intellectual movements, and identified five thematic clusters ("Perception of Counseling Services", "Appearance and Reality in Sociocultural Evolution," "Cultural Heritage and Identity," "Media and Culture," and "Cultural Identity"), all with theoretical and pragmatic implications which we discuss. A deeper look at these clusters reveals new empirical questions and promising directions for future research.

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections.

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion-extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion-extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.

Atypical Rasmussen's Encephalitis.

A three-year-old female patient was admitted to our institution due to subacute fever, intermittent vomiting, persistent bilateral mydriasis after cycloplegia, right central facial palsy, and mild right hemiparesis with hyperreflexia. Brain MRI shows encephalitis in frontal, parietal, insular, and left putamen course and loss of cortical volume and white matter of the entire left hemisphere which are features described in Rasmussen's encephalitis (RE). Therapy with intravenous methylprednisolone bolus was initiated, with adequate clinical response. We consider in this case the diagnosis of atypical RE by imaging criteria in the subacute stage. There are few reports of atypical RE without epilepsy or continuous partial epilepsy. Our purpose is to present a case of a patient with RE images without epilepsy seizures and review the diagnostic and therapeutic approach of RE.

Artificial neural network modelling hydrodenticity for optimal design by microfluidics of polymer nanoparticles to apply in magnetic resonance imaging.

The engineering of nanoparticles impacts the control of their nano-bio interactions at each level of the delivery pathway. Therefore, optimal nanoparticle physicochemical properties should be identified to favour on-target interactions and deliver efficiently active compounds to a specific target. To date, traditional batch processes do not guarantee the reproducibility of results and low polydispersity index of the nanostructures, while microfluidics has emerged as cost effectiveness, short-production time approach to control the nanoparticle size and size distribution. Several thermodynamic processes have been implemented in microfluidics, such as nanoprecipitation, ionotropic gelation, self-assembly, etc., to produce nanoparticles in a continuous mode and high throughput way.   In this work, we show how the Artificial Neural Network (ANN) can be adopted to model the impact of microfluidic parameters (namely, flow rates and polymer concentrations) on the size of the nanoparticles. Promising results have been obtained, with the highest model accuracy reaching 98.9 %, thus confirming the proposed approach's potential applicability for an ANN-guided biopolymer nanoparticle design for biomedical applications. Nanostructures with different degrees of complexity are analysed, and a proof-of-concept machine learning approach is proposed to evaluate Hydrodenticity in biopolymer matrices. STATEMENT OF SIGNIFICANCE: Size, shape and surface charge determine nano-bio interactions of nanoparticles and their ability to target diseases. The ideal nanoparticle design avoids off-target interactions and favours on-target interactions. So, tools enabling the identification of the optimal nanoparticle physicochemical properties for delivery to a specific target are required. In this work, we evaluate the use of Artificial Neural Network (ANN) to analyse the role of microfluidic parameters in predicting the optimal size of the different hydrogel nanoparticles and their ability to trigger Hydrodenticity.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. AIM: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. METHODS: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. RESULTS: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). CONCLUSIONS: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.