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Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood. Currently, it is understood that certain pituitary neuroendocrine tumors (PitNETs) exhibit a hereditary predisposition. These tumors’ genetic patterns fall into two categories: isolated and syndromic tumors. The isolated forms are characterized by molecular defects that predispose exclusively to PitNETs, including familial isolated pituitary adenomas (FIPAs) and sporadic genetic defects not characterized by hereditary predisposition. All the categories involve either germline or somatic mutations, or both, each associated with varying levels of penetrance and different phenotypes. This highlights the importance of genetic testing and the need for a more comprehensive view of the whole disease. Despite the availability of multiple treatment options, diagnosis often occurs after several years, and management is still difficult. Early detection and intervention are crucial for preventing complications and enhancing the quality of life for affected individuals. This review aims to elucidate the molecular, clinical, and histological characteristics of GH-secreting PitNETs, providing insights into their prevalence, treatment nuances, and the benefits of genetic testing for each type of genetic disorder associated with acromegaly.

Background: Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain. Discussion: Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity. Conslusions: This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders.

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs—miR-199a, miR-20a, and miR-30c—in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.

Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. Material and methods: This case–control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). Results: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. Conclusions: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients.

Worldwide, breast cancer (BC) is one of the most common cancers in women and is responsible for the highest number of cancer-related deaths among women, with a special clinical behavior and therapy response. Triple-negative breast cancer (TNBC) is seen as a highly invasive BC, characterized by a short survival, higher mortality, recurrence, and metastasis when it is compared to the other BC subtypes. The molecular subtyping of TNBC based on mRNA expression levels does not accurately reflect protein expression levels, which impacts targeted therapy effectiveness and prognostic predictions. Most TNBC cases exhibit a high frequency of homologous recombination (HR) DNA repair deficiency (HRD) signatures and are associated with a complex genomic profile. Biomarker research in TNBC includes investigating genetic mutations, gene expression patterns, immune system-related markers, and other factors that can provide valuable information for diagnosis, treatment selection, and patient outcomes. Additionally, these biomarkers are often crucial in the development of personalized and precision medicine approaches, where treatments are customized to each patient’s unique characteristics. This ongoing research is essential for improving the management and outcomes of TNBC, which is a challenging and heterogeneous form of breast cancer. The findings of this research have practical implications for refining treatment strategies, particularly in selecting appropriate systemic therapies and integrating traditional treatment modalities like surgery and radiotherapy into comprehensive care plans for TNBC patients.

Epicardial adipose tissue (EAT) is a unique fat depot located around the heart, intimately associated with the myocardium and coronary arteries. The secretion of bioactive molecules and their interaction with neighbouring cardiac tissues makes it an active organ with important implications in cardiovascular health and disease. In recent years, omics technologies have provided valuable insights into the molecular characteristics and functional relevance of EAT in patients with coronary atherosclerosis, myocardial infarction, atrial fibrillation and associated metabolic disorders. This review aims to summarize the current understanding of EAT biology through the lens of genomics, transcriptomics, proteomics and lipidomics approaches. We discuss key findings from omics studies on EAT, including gene expression profiles, metabolic activity, signalling pathways and regulatory network, in order to explore in depth the disease mechanisms, possible therapeutic strategies, and cardiovascular risk assessment. Further advances in this field and integrating data from multiple omics platforms hold promise for unlocking personalized cardiometabolic profiles with EAT as a possible biomarker and therapeutic target in cardiovascular disease.

Background: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. Methods: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched—Web of Science, Medline, and EMBASE—for the studies assessing CLTI and the biological markers related to it. Results: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. Conclusions: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Background: Breast cancer is the most frequently diagnosed cancer among women, responsible for the highest number of cancer-related deaths worldwide. There is limited data available related to serum tumor markers in breast cancer and other blood parameters or other glandular laboratory parameters. This study aims to evaluate the correlation of tumor-specific markers for breast cancer with other blood parameters and how these correlations could impact clinical management. Material and Method: This retrospective study represents a data analysis from 1 January 2020 to 31 May 2023, in the County Hospital of Timisoara, Romania. We reviewed all the cases where, in the laboratory analyses, the serum tumor specific biomarkers for breast cancer were analyzed. Results: A statistical analysis was performed in order to identify a possible relationship between CA 15-3 and the various biomarkers and blood parameters included in the present study. Values were classified according to reference ranges. The tests revealed no statistically significant associations between CA 15-3 values and the levels of CA125 (χ2(1) = 1.852, p = 0.174), CEA (χ2(1) = 1.139, p = 0.286), AFP (Fisher’s exact test, p = 0.341), fT4 (Fisher’s exact test, p = 0.310), TSH (Fisher’s exact test, p = 0.177), or PTH (Fisher’s exact test, p = 0.650). Conclusion: The findings indicate a lack of strong correlation between CA 15-3 and CA125, CEA, AFP, thyroid function markers, or PTH within this cohort.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual’s lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000–2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), cadmium (Cd), and lead (Pb) levels were measured in the Bor City water supply system (control) and two watercourses exposed to mining wastewaters, i.e., the Lutarica River (one site) and the Kriveljska River (two sites). The same parameters were determined in the brain, heart, lungs, stomach, liver, spleen, kidneys, and testes of male Wistar rats given water from these sources for 2 months. Water Cu, Fe, Cd, and Pb were outside the safe range, excepting the reference site. Significant impacts on intra-organ metal homeostasis were detected, especially in the brain, stomach, kidneys, and testes. The dynamics and magnitude of these changes (versus controls) depended on the target organ, analyzed metal, and water origin. The greatest number of significant intra-organ associations between essential and non-essential metals were found for Cd-Zn, Cd-Cu, and Cd-Mn. A regression analysis suggested the kidneys as the most relevant organ for monitoring water manganese, and the stomach and brain for lead. These results highlight the environmental risks associated with mining wastewaters from the Bor area and could help scientists in mapping the spatial distribution and severity of trace metal contamination in water sources.

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3–31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples’ color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects.

Background: Helicobacter pylori antibiotic resistance has increased worldwide and affects the effectiveness of current therapies. The recommended first-line empiric treatment should be tailored to the local clarithromycin resistance rate. This study aimed to determine the pediatric patient profile and rate of clarithromycin resistance for patients diagnosed with Helicobacter pylori by gastric biopsy. Methods: We studied 84 positive gastric samples for Helicobacter pylori. Positive results were confirmed by a rapid urease test and histopathological examination, with the type of gastritis established according to the Sydney System. Gastric biopsy samples were stored in RNA saver. Clarithromycin resistance was determined by a real-time polymerase chain reaction-based molecular assay after RNA-DNA extraction. Results: Of the 84 biopsy samples analyzed, 35 (41.6%) were resistant to clarithromycin. Clarithromycin resistance was found mainly in girls (80%) with a mean age of 15 years (range 6–17 years). The history of prior exposure to clarithromycin was 91.6%. The concordance between the histopathological examination and the PCR test was 100%. Conclusions: One in 2.4 children infected with Helicobacter pylori had a strain resistant to clarithromycin. This resistant strain may be a reason for treatment failure in Romanian children, yet this is uninvestigated. The high rate of bacterial resistance to this antibiotic among children indicates the need for susceptibility testing before therapy.

Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood–brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction.

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis. Mitochondria are responsible for the majority of cellular ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, cellular aging, and cancer. In this article, we describe the pathophysiological changes in, and mitochondrial role of, metabolic disorders (diabetes, obesity, and cardiovascular disease) and their correlation with oxidative stress. We highlight the genetic changes identified at the mtDNA level. Additionally, we selected several representative biomarkers involved in oxidative stress and summarize the progress of therapeutic strategies.

Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

Background and objectives: The postpartum maternal physical and psychological state played a fundamental role in the mother–child relationship at the beginning of the COVID-19 pandemic. The aim of the study is to analyze the influence of maternal psychological manifestations on the mother–child couple through three objectives (briefly expressed): (I) Determination of the main acute and chronic conditions of newborns/infants. (II) Verification of the hypothesis of the existence of a link between the following neonatal variables: gestational age, birth weight, number of days of hospitalization, and specific neonatal therapies (oxygen, surfactant, and blood products’ transfusion). (III) Verification of the influence of postpartum maternal psychological status on the mother–child couple through three hypotheses. Materials and methods: This cross-sectional study was conducted in two hospitals in Timișoara, Romania, between 1 March and 1 September 2020, and included 165 mothers and their 175 newborns. Mothers answered the Edinburgh Postnatal Depression Scale, Spielberger’s Inventory of State-Trait Anxiety, and the Collins and Read Revised Adult Attachment Scale. Results: (I) The acute and chronic pathology of the infants in the study group was polymorphic. (II) Large correlations were identified between the following infant variables: gestational age with birth weight, and number of hospitalization days with birth weight, gestational age, and use of blood product transfusion (all p < 0.001). (III) (1) State anxiety was the only significant predictor of number of hospitalization days (p = 0.037), number of acute disorders (p = 0.028), and number of infant chronic diseases (p = 0.037). (2) Maternal depressive symptoms were the only predictor of postpartum maternal attachment (p = 0.018). (3) Depressive symptoms, state, and trait anxiety were non-significant in all models studied (all p > 0.05). Conclusions: Postpartum maternal physical and psychological state plays a fundamental role on the mother–child relationship in the new social and complex family conditions.

With the onset of the COVID-19 pandemic, enormous efforts have been made to understand the genus SARS-CoV-2. Due to the high rate of global transmission, mutations in the viral genome were inevitable. A full understanding of the viral genome and its possible changes represents one of the crucial aspects of pandemic management. Structural protein S plays an important role in the pathogenicity of SARS-CoV-2, mutations occurring at this level leading to viral forms with increased affinity for ACE2 receptors, higher transmissibility and infectivity, resistance to neutralizing antibodies and immune escape, increasing the risk of infection and disease severity. Thus, five variants of concern are currently being discussed, Alpha, Beta, Gamma, Delta and Omicron. In the present review, a comprehensive summary of the following critical aspects regarding SARS-CoV-2 has been made: (i) the genomic characteristics of SARS-CoV-2; (ii) the pathological mechanism of transmission, penetration into the cell and action on specific receptors; (iii) mutations in the SARS-CoV-2 genome; and (iv) possible implications of mutations in diagnosis, treatment, and vaccination.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

Wolf–Hirschhorn syndrome (WHS), a rare disorder determined by distal 4p deletion, is characterized by a pre and postnatal growth retardation, hypotonia, intellectual disability, epilepsy, craniofacial dysmorphism, and congenital fusion anomalies. The clinical aspects are dependent on the deletion’ size. Our aim was to identify rare specific characteristics in a cohort of seven cases with 4p deletion and to assess the utility of Multiplex ligation-dependent probe amplification (MLPA) (cheap and sensitive test)—combined kits—as a diagnostic test and selection tool for cases that require other investigations (chromosomal microarray analysis—CMA, karyotype). For all cases we conducted a clinical examination with the main features identified: facial dysmorphism, intellectual disability, postnatal development delay, cardiac defects and hypotonia. In some cases, we observed seizures, structural brain abnormalities, immunodeficiencies, and renal anomalies. Prenatal growth retardation was detected in a relatively small number of cases, but postnatal growth failure was a constant feature. In all cases, the clinical diagnosis was confirmed by genetic analyses: karyotype and/or MLPA. In conclusion, renal and brain defects, as well as immunodeficiency are rare manifestations and should be looked for. Although CMA is the standard test, in our experience, MLPA is also a reliable screening method as the identified cases were either confirmed by MLPA or selected for further investigations.

The tumor microenvironment (TME) influences cancer progression. Therefore, engineered TME models are being developed for fundamental research and anti-cancer drug screening. This paper reports the biofabrication of 3D-printed avascular structures that recapitulate several features of the TME. The tumor is represented by a hydrogel droplet uniformly loaded with breast cancer cells (106 cells/mL); it is embedded in the same type of hydrogel containing primary cells—tumor-associated fibroblasts isolated from the peritumoral environment and peripheral blood mononuclear cells. Hoechst staining of cryosectioned tissue constructs demonstrated that cells remodeled the hydrogel and remained viable for weeks. Histological sections revealed heterotypic aggregates of malignant and peritumoral cells; moreover, the constituent cells proliferated in vitro. To investigate the interactions responsible for the experimentally observed cellular rearrangements, we built lattice models of the bioprinted constructs and simulated their evolution using Metropolis Monte Carlo methods. Although unable to replicate the complexity of the TME, the approach presented here enables the self-assembly and co-culture of several cell types of the TME. Further studies will evaluate whether the bioprinted constructs can evolve in vivo in animal models. If they become connected to the host vasculature, they may turn into a fully organized TME.

Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA (E. coli) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids’ migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs (p > 0.05). The presence of plasmids qnrA, qnrB, and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer.

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

Pulmonary Alveolar Proteinosis (PAP) is a rare, usually autoimmune, disease, where surfactant accumulates within alveoli due to decreased clearance, causing dyspnea and hypoxemia. The disease is even more rare in pregnancy; nevertheless, it has been reported in pregnant women and can even appear for the first time during pregnancy as an asthma-like illness. Therefore, awareness is important. Similarly to many autoimmune diseases, it can worsen during pregnancy and postpartum, causing maternal and fetal/neonatal complications. This paper offers a narrative literature review of PAP and pregnancy, while illustrating a case of a pregnant patient with known PAP who developed preeclampsia in the third trimester but had an overall fortunate maternal and neonatal outcome.

Background and Objectives: In this study, we investigated the changes of platelet count and other platelet indices, such as mean platelet volume (MPV), in cases with severe early intrauterine fetal growth restriction (IUGR). Materials and Methods: We retrospectively analyzed all pregnancies diagnosed with severe early onset IUGR, that were followed up in our hospital between 2010 and 2015 (before implementation of screening and prophylaxis with aspirin). Pregnancies which resulted in birth of a newborn with a birthweight less than 5th percentile for gestational age, that required delivery for fetal or maternal indication before 32 weeks, were selected for the IUGR group. The IUGR cases were divided into two groups according to preeclampsia (PE) association. All cases with a complete blood count (CBC) performed within 7 days prior to delivery were included in the study, as the IUGR group. The control group included normal singleton pregnancies, delivered at term, with birthweight above 10th centile and a CBC taken at 30–32 weeks. Results: There was a significant difference in platelet count and MPV values between the IUGR group and control. Cases with IUGR presented lower platelet count and higher MPV values; there was no significant difference of these parameters when PE was associated with IUGR. Conclusions: Our results suggest that in cases of severe early IUGR, even in the absence of clinically diagnosed PE, there may be maternal endothelial damage and platelet consumption in the systemic and uteroplacental circulation. Platelet count and MPV values are simple and widely available laboratory tests that might be used as indicator of placental insufficiency; however, prospective data are required to establish the mechanistic link and to which extent these parameters are good predictors of severity or adverse perinatal outcomes.

After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity—humoral and cellular, innate and adaptive—underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed.

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio < 13.80 (n = 39) and group 2 with an E/e’ ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio.

Background: The first admission for acute heart failure with preserved ejection fraction (HFpEF) drastically influences the short-term prognosis. Baseline characteristics may predict repeat hospitalization or death in these patients. Methods: A 103 patient-cohort, admitted for the first acute HFpEF episode, was monitored for six months. Baseline characteristics were recorded and their relation to the primary outcome of heart failure readmission (HFR) and secondary outcome of all-cause mortality was assessed. Results: We identified six independent determinants for HFR: estimated glomerular filtration rate (eGFR) (p = 0.07), hemoglobin (p = 0.04), left ventricle end-diastolic diameter (LVEDD) (p = 0.07), E/e’ ratio (p = 0.004), left ventricle outflow tract velocity-time integral (LVOT VTI) (p = 0.045), and diabetes mellitus (p = 0.06). Three of the variables were used to generate a risk score for HFR: LVEDD, E/e’, LVOT VTI -DEI Score = − 28.763 + 4.558 × log (LVEDD (mm)) + 1.961 × log (E/e’ ratio) + 1.759 × log (LVOT VTI (cm)). Our model predicts a relative amount of 20.50% of HFR during the first 6 months after the first acute hospitalization within the general population with HFpEF with a DEI Score over −0.747. Conclusions: We have identified three echocardiographic parameters (LVEDD, E/e’, and LVOT VTI) that predict HFR following an initial acute HFpEF hospitalization. The prognostic DEI score demonstrated good accuracy.

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

The presence of maternal Anti-Ro/Anti-La antibodies causes a passively acquired autoimmunity that may be associated with serious fetal complications. The classic example is the autoimmune-mediated congenital heart block (CHB) which is due in most cases to the transplacental passage of Anti-Ro/Anti-La antibodies. The exact mechanisms through which these pathologic events arise are linked to disturbances in calcium channels function, impairment of calcium homeostasis and ultimately apoptosis, inflammation and fibrosis. CHB still represents a challenging diagnosis and a source of debate regarding the best management. As the third-degree block is usually irreversible, the best strategy is risk awareness and prevention. Although CHB is a rare occurrence, it affects one in 20,000 live births, with a high overall mortality rate (up to 20%, with 70% of in utero deaths). There is also concern over the lifelong consequences, as most babies need a pacemaker. This review aims to offer, apart from the data needed for a better understanding of the issue at hand, a broader perspective of the specialists directly involved in managing this pathology: the rheumatologist, the maternal–fetal specialist and the cardiologist. To better illustrate the theoretical facts presented, we also include a representative clinical case.

The term allergic angina, introduced for the first time by Nicholas Kounis in 1991, initially referred to the coexistence of acute coronary syndromes with allergy or hypersensitivity. At present, it is believed that Kounis syndrome is a particular case of systemic disease, with multiorgan arterial involvement generated during immediate hypersensitivity reactions. Myocardial bridging (MB), a condition that can induce coronary artery spasm, has long been regarded as a benign condition. Since both pathologies are associated with arterial spasm, Kounis syndrome and MB are considered to be confounding pathologies for acute coronary syndromes, and their association is quite a rare finding. To date, there are no precise data on the epidemiology, and the population affected by Kounis syndrome seems to be highly heterogeneous. Since this is a rare disease, even less is known about possible different phenotypes, including MB overlap. We report a case of type I variant Kounis syndrome associated with MB with no evidence of coronary artery disease, occurring as late presentation, following a severe systemic reaction (anaphylaxis) induced by a Hymenoptera sting. At present, only two other cases of type I and one case of type II Kounis syndrome occurring in patients with myocardial bridging have been described.