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The globally important marine diazotrophic cyanobacterium Trichodesmium is abundant in the New Caledonian lagoon (southwestern Pacific Ocean) during austral spring/summer. We investigated the cellular processes mediating Trichodesmium mortality from large surface accumulations (blooms) in the lagoon. Trichodesmium cells (and associated microbiota) were collected at the time of surface accumulation, enclosed under simulated ambient conditions, and sampled over time to elucidate the stressors and subcellular underpinning of rapid biomass demise (> 90 % biomass crashed within ∼ 24 h). Metatranscriptomic profiling of Trichodesmium biomass, 0, 8 and 22 h after incubations of surface accumulations, demonstrated upregulated expression of genes required to increase phosphorus (P) and iron (Fe) availability and transport, while genes responsible for nutrient storage were downregulated. Total viral abundance oscillated throughout the experiment and showed no significant relationship with the development or demise of the Trichodesmium biomass. Enhanced caspase-specific activity and upregulated expression of a suite of metacaspase genes, as the Trichodesmium biomass crashed, implied autocatalytic programmed cell death (PCD) as the mechanistic cause. Concurrently, genes associated with buoyancy and gas vesicle production were strongly downregulated concomitant with increased production and high concentrations of transparent exopolymeric particles (TEP). The rapid, PCD-mediated, decline of the Trichodesmium biomass, as we observed from our incubations, parallels mortality rates reported from Trichodesmium blooms in situ. Our results suggest that, whatever the ultimate factor, PCD-mediated death in Trichodesmium can rapidly terminate blooms, facilitate aggregation, and expedite vertical flux to depth.

A one-dimensional two-phase Stefan problem for the melting of a semi-infinite material with a power-type temperature-dependent thermal conductivity was considered. The assumption of taking thermal parameters as functions of temperature found its basis in physical and industries applications, allowing for a more precise and realistic description of phase change processes. By imposing a Dirichlet condition at the fixed face, a theoretical and approximate study was developed. Through a similarity transformation, an equivalent ordinary differential problem was obtained from which an integral problem was deduced. The existence of at least one analytical solution was guaranteed by using the Banach fixed point theorem. Due the unavailability of an analytical solution, a heat balance integral method was applied, assuming a quadratic temperature profile in space, to simulate temperature variations and the location of the interface during the melting process. For constant thermal conductivity, results can be compared with the exact solution available in the literature to check the accuracy of the approximate method.

The aim of the study was to compare the efficacy and safety of singledose prulifloxacin vs. single-dose pefloxacin in the treatment of patients with acute uncomplicated urinary tract infections. Two hundred and thirty-one female out-patients were considered microbiologically evaluable and randomly treated with 600 mg prulifloxacin (116 patients) or 800 mg pefloxacin (115 patients). The most commonly isolated uropathogen at baseline was Escherichia coli (71.4%), followed by Proteus mirabilis (10.8%) and Klebsiella pneumoniae (7.8%). Five-seven days posttreatment, the eradication rate was 97.4% and 92.2% in the prulifloxacin and pefloxacin group, respectively. The one-tailed 95% confidence interval analysis showed the equivalence of treatments. Four weeks from treatment no relapses, reinfections or superinfections were observed. The clinical success rates were 92.2% in the prulifloxacin and 84.3% pefloxacin groups. The safety profile was very good with both drugs. The results of the study make it possible to consider prulifloxacin a possible therapeutic option in patients with acute uncomplicated UTIs.

We consider two one-phase nonlinear one-dimensional Stefan problems for a semi-infinite material x > 0; with phase change temperature Tf : We assume that the heat capacity and the thermal conductivity satisfy a Storm’s condition. In the first case, we assume a heat flux boundary condition of the type [PLEASE CHECK FORMULA IN THE PDF], and in the second case, we assume a temperature boundary condition T = Ts < Tf at the fixed face. Solutions of similarity type are obtained in both cases, and the equivalence of the two problems is demonstrated. We also give procedures in order to compute the explicit solution.

Abstract  This study describes an original surgical technique for the correction of medium/high-degree cystocele using a tension-free way to apply a polypropylene mesh: the “tension-free cystocele repair” (TCR). About 218 patients were available with a mean follow-up of 38 months. This technique showed an elevated rate of anatomic correction (75.7%), a statistically significant correction of storage symptoms (48.6 vs 32.5%, p p p [ABSTRACT FROM AUTHOR]

Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sense mechanical cues, while mechanotransduction is the capacity of a cell to respond to these signals by translating mechanical stimuli into biochemical ones. These signals propagate from the extracellular matrix to the nucleus with different well known physical connections, but how the mechanical signals are transduced into biochemical ones remains an open challenge. Recent findings showed that the cell-generated forces affect the translocation of transcription factors (TFs) from the cytoplasm to the nucleus. This mechanism is affected by the features of nuclear pore complexes. Owing to the complex patterns of strains and stresses of the nuclear envelope caused by cytoskeletal forces, it is likely that the morphology of NPC changes as cytoskeleton assemblies’ change. This may ultimately affect molecular transport through the nucleus, hence altering cell functions. Among the various TFs, Yes-associated protein (YAP), which is typically involved in cell proliferation, survival, and differentiation, is able to activate specific pathways when entrapped into the cell nucleus. Here, starting from experimental results, we develop a multiscale finite element (FE) model aimed to simulate the macroscopic cell spreading and consequent changes in the cell mechanical behaviour to be related to the NPCs changes and YAP nuclear transport.

In this article, we define a p-generalized modified error function as the solution to a non-linear ordinary differential equation of second order, with a Robin type boundary condition at x=0. We prove existence and uniqueness of a non-negative $C^{\infty}$ solution by using a fixed point argument. We show that the p-generalized modified error function converges to the p-modified error function defined as the solution to a similar problem with a Dirichlet boundary condition. In both problems, for p=1, the generalized modified error function and the modified error function are recovered. In addition, we analyze the existence and uniqueness of solution to a problem with a Neumann boundary condition.

The extracellular microenvironment proved to exert a potent regulatory effect over different aspects of Embryonic Stem Cells (ESCs) behavior. In particular, the employment of engineered culture surfaces aimed at modulating ESC self-organization resulted effective in directing ESCs toward specific fate decision. ESCs fluctuate among different levels of functional potency and in this context the Zscan4 gene marks the so-called “metastate,” a cellular state in which ESCs retain both self-renewal and pluripotency capabilities. Here we investigated the impact of topographic cues on ESCs pluripotency, differentiation and organization capabilities. To this aim, we engineered culturing platforms of nanograted surfaces with different features size and we investigated their impact on ESCs multicellular organization and Zscan4 gene expression. We showed that the morphology of ESC-derived aggregates and Zscan4 expression are strictly intertwined. Our data suggest that ESC Zscan4 metastate can be promoted if the adhesive surface conditions guide cellular self-aggregation into 3D dome-like structure, in which both cell-material interactions and cell-cell contact are supportive for Zscan4 expression.

A systematic European Union (EU)-wide data framework for the collection of fisheries data in support of the EU Common Fisheries Policy (CFP) was first implemented in 2002. Since that time, EU data collection regulation has undergone 2 revisions in response to evolving policy needs. The European Commission’s Joint Research Centre (JRC) is responsible for conducting research and providing advice on fisheries management under the CFP, and since 2005 has worked closely with the Scientific, Technical and Economic Committee for Fisheries (STECF). JRC and STECF have an open data policy, and aggregated data submitted by EU member states in response to data calls issued under the provisions of the data collection regulation are published via the website of the STECF. This paper provides an overview of the fisheries data activities carried out by the JRC in support of and in collaboration with the STECF and discusses some of the benefits and drawbacks of such activities.

Background: Heart failure (HF) is a chronic-progressive disease. Once established, it is almost impossible to obtain a restitutio ad integrum of the cardiac function, but current strategies aim at slowing down the progression towards the terminal stages of the disease, which inevitably lead to the exitus. On the basis of these considerations, it appears clear that pharmacological interventions applied in this clinical condition should prevent first the development of the disease, by controlling the risk factors for HF thus reducing the onset of the disease, second slowing the disease evolution towards the terminal phases thus containing clinical symptoms and reducing the number of hospitalizations. In this scenario, the add-on therapy with vericiguat seems promising as reported in the VICTORIA study without affecting renal function. Several evidence indicates that renal arterial resistance index (RRI) seems to better reflect cardiovascular damage also in HF patients, thus affecting patients prognosis METHODS: In the present study we have analyzed the effect of vericiguat administration in 27 HF patients specifically evaluating RRI., Results: Vericiguat signicantly reduces RRI., Conclusions: The findings of the present study seems to indicate that vericiguat, beyond its primary mechanism of action, might offer an additional advantage in HF patients., Competing Interests: Declaration of competing interest This work receives no specific funds. Authors have no conflicts of interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the impact of Fabry disease (FD) on retinal microvasculature using optical coherence tomography angiography (OCTA), arterial stiffness, and the resistive index (RI) of the central retinal artery (CRA) in early disease stages. Twenty-nine genetically confirmed FD patients and twenty-six healthy controls were enrolled. Vessel density (VD) values of the superficial, deep, and choriocapillaris plexuses (SCP, DCP, and CC) were measured via OCTA. CRA RI was studied using color Doppler and grayscale sonography, and aortic pulse wave velocity (PWV) was assessed with the Complior method. CRA RI was significantly lower in the control group compared to the Fabry group (p < 0.001). Central VD was found to be significantly higher in the control group compared to the Fabry group in all the retinal layers (SCP (p < 0.001), DCP (p < 0.005), CC (p < 0.001)). PWV was significantly higher in the Fabry group than in the control group (p = 0.03). Fabry disease patients demonstrate elevated arterial stiffness, increased CRA RI, and diminished retinal microvascular density compared to healthy controls, indicating early ocular damage. Continuous monitoring and targeted screening for organ impairment are crucial in FD management. Identifying biomarkers for assessing ocular vascular involvement and treatment response is imperative. Further research is needed., (© 2024. The Author(s).)

Arterial hypertension remains the major cardiovascular risk worldwide. It is estimated that under 50 years of age one in every three adults is hypertensive while beyond the age of 50 the prevalence is almost 50% globally. The latest World Health Organization (WHO) Global Report on Hypertension indicated that the global number of hypertensive patients almost doubled in the last three decades, with related increasing deaths, disability, and costs annually. Because of this global increase, early diagnosis and timely treatment is of great importance. However, based on the WHO Global Report, it is estimated that up to 46% of individuals were never diagnosed. Of those diagnosed, less than 50% were on treatment, with nearly half among these at target according to the current guidelines. It is also important to note that an increasing number of hypertensive patients, despite the use of three or more drugs, still do not achieve a blood pressure normalization, thus defining the clinical scenario of resistant hypertension (RH). This condition is associated to a higher risk of hypertension-mediated organ damage and hospitalization due to acute cardiovascular events. Current guidelines recommend a triple combination therapy (renin angiotensin system blocking agent + a thiazide or thiazide-like diuretic + a dihydropyridinic calcium-channel blocker) to all patients with RH. Beta-blockers and mineralocorticoid receptor antagonists, alone or in combination, should be also considered based on concomitant conditions and potential contraindications. Finally, the renal denervation is also proposed in patients with preserved kidney function that remain hypertensive despite the use of maximum tolerated medical treatment. However, the failure of this procedure in the long term and the contraindication in patients with kidney failure is a strong call for a new therapeutic approach. In the present review, we will discuss the pharmacological novelties to come for the management of hypertension and RH in the next future.

Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific cause remains unidentified. Recent research has highlighted the potential role of genetic susceptibility in the development of myocarditis (and in some cases the development of inflammatory dilated cardiomyopathy, i.e., the condition in which there is chronic inflammation (>3 months) and left ventricular dysfunction\dilatation), with several studies indicating a correlation between myocarditis and genetic backgrounds. Notably, pathogenic genetic variants linked to dilated or arrhythmic cardiomyopathy are found in 8-16% of myocarditis patients. Genetic predispositions can lead to recurrent myocarditis and a higher incidence of ventricular arrhythmias and heart failure. Moreover, the presence of DSP mutations has been associated with distinct pathological patterns and clinical outcomes in arrhythmogenic cardiomyopathy (hot phases). The interplay between genetic factors and environmental triggers, such as viral infections and physical stress, is crucial in understanding the pathogenesis of myocarditis. Identifying these genetic markers can improve the diagnosis, risk stratification, and management of patients with myocarditis, potentially guiding tailored therapeutic interventions. This review aims to synthesize current knowledge on the genetic underpinnings of myocarditis, with an emphasis on desmoplakin-related arrhythmogenic cardiomyopathy, to enhance clinical understanding and inform future research directions.

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD). In comparison to the control group fed with standard diet, we observed 69 miRNAs exhibiting increased expression and 63 showing decreased expression in the HFD mice's hippocampus. Through bioinformatics analysis, we identified numerous potential targets of the dysregulated miRNAs, pinpointing a subset of genes regulating neuroplasticity that were targeted by multiple differentially modulated miRNAs. We also validated the expression of these synaptic and non-synaptic proteins, confirming the downregulation of Synaptotagmin 1 (SYT1), calcium/calmodulin dependent protein kinase I delta (CaMK1D), 2B subunit of N-methyl-D-aspartate glutamate receptor (GRIN2B), the DNA-binding protein Special AT-Rich Sequence-Binding Protein 2 (SATB2), and RNA-binding proteins Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and Neuro-oncological ventral antigen 1 (NOVA1) in the hippocampus of HFD mice. In summary, our study offers a snapshot of the HFD-related miRNA landscape potentially involved in the alterations of brain functions associated with metabolic disorders. By shedding light on the specific miRNA-mRNA interactions, our research contributes to a deeper understanding of the molecular mechanisms underlying the effects of HFD on the synaptic function., (© 2024. The Author(s).)

Background: Degenerative aortic valve stenosis (AS) is the most common valvular heart disease among the elderly. Once cardiac symptoms occur, current guidelines recommend aortic valve replacement. Progressive degeneration/calcification reduces leaflet mobility with gradual cardiac output (CO) impairment. Low CO might induce abnormal brain-aging with cognitive impairment and increased risk of dementia, such as Alzheimer's disease or vascular dementia. On the contrary, cognitive improvement has been reported in patients in whom CO was restored. Transcatheter aortic valve implantation (TAVI) has proven to be a safe alternative to conventional surgery, with a similar mid-term survival and stroke risk even in low-risk patients. TAVI is associated with an immediate CO improvement, also effecting the cerebrovascular system, leading to an increased cerebral blood flow. The correlation between TAVI and cognitive improvement is still debated. The present study aims at evaluating this relationship in a cohort of AS patients where cognitive assessment before and after TAVI was available., Methods: a total of 47 patients were retrospectively selected. A transcranial Doppler ultrasound (TCD) before and after TAVI, a quality of life (QoL) score, as well as a mini-mental state examination (MMSE) at baseline and up to 36 months, were available., Results: TAVI was associated with immediate increase in mean cerebral flow at TCD. MMSE slowly increase at 36-months follow-up with improved QoL mainly for symptoms, emotions and social interactions., Conclusions: this proof-of-concept study indicates that TAVI might induce cognitive improvement in the long-term as a result of multiple factors, such as cerebral flow restoration and a better QoL.

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and "rapid" achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of "go lower, start earlier and keep longer!" should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score., Competing Interests: The authors declare no conflicts of interests.

Cardiovascular diseases remain the main cause of death and disability worldwide. Despite the tremendous improvement in pharmacological, minimally invasive and rehabilitative strategies, global deaths due to cardiovascular diseases are still increasing. Additional risk factors have been recently proposed, and thanks to scientific progress, novel drugs for the control of the main risk factors focusing on the cardiometabolic pathways have been identified. Glucagon-like peptide-1 (GLP-1) receptor agonists represent an innovative step in the management of patients affected by type 2 diabetes mellitus. In addition to their significant efficacy on glycemic homeostasis, some members of this class of drugs have indications in the treatment of obesity. Furthermore, accumulated evidence in the literature has finally suggested a protective role in cardiovascular health. The possible role of GLP-1R agonist drugs (GLP-1RAs) on the mechanisms underlying chronic inflammation and the almost ubiquitous distribution of GLP-1 receptors could explain the enormous versatility of these drugs. Semaglutide is a GLP-1RA recently proven to be effective in cardiovascular outcomes. In the present article, we will review the available data on semaglutide in light of the most recent publications to better characterize the target population achieving cardiovascular benefits.

The polypill strategy, which combines several medicines that simultaneously control different risk factors/diseases in a single pill, is one of the approaches used in cardiovascular therapy. In different guidelines, this one-pill combination therapy is suggested as first-line step in disease management. Because the cardiovascular diseases (CVD) pandemia, prevention is essential. The approaches that could improve adherence are of great importance to achieve health, social and economical benefits. However, direct or indirect experience of adverse drug reaction is often the reason for discontinuation, with serious fatal and non-fatal consequences especially for a polypill. Angiotensin-converting enzyme inhibitors (ACEi) and statins are the most prescribed medications in CVD prevention. It is well known that both drugs may have adverse effects that induce discontinuation. Often, the personal awareness of these effects is a reason for self-discontinuation. In this study an analysis of the ACEi/statin awareness is reported. Is it potentially harmful for polypill?, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Retinal angiopathy represents a well-known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Until recently, there have been no reports on retinal changes in ATTRwt. In this retrospective observational clinical study, we aimed to determine whether vessel density (VD) indices and the choroidal vascularity index (CVI) could offer insights into retinal and choroidal vascular changes among patients affected by ATTRwt., Methods: Eighteen patients with a confirmed diagnosis of ATTRwt underwent structural optical coherence tomography (OCT) and OCT angiography (OCTA). We established a control group consisting of 16 healthy subjects for statistical comparisons. The 3D OCT and OCTA datasets were analyzed to assess retinal and choroidal thickness and VD. For measuring CVI, we obtained measurements for the total choroid area (TCA), luminal area (LA), and stromal area (SA)., Results: The mean VD exhibited a statistically significant reduction in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) among the ATTRwt group in comparison to the control group ( p < 0.0001). Notably, ATTRwt patients displayed decreased choroidal thickness ( p = 0.08). Additionally, the median CVI was lower in the ATTRwt group than in the control group ( p = 0.04)., Conclusion: The indices from OCTA and CVI have the potential to serve as non-invasive biomarkers for the quantitative evaluation of retinal and choroidal vascular involvement in patients with ATTRwt., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rinaldi, Tranfa, Chiosi, Campagna, De Bernardo, Gioia, Natale, Caiazza, Dongiglio, Verrillo, Palmiero, Limongelli and Costagliola.)

The cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models to evaluate the molecular mechanisms of cardiac regeneration, we used cryoinjury on rat Engineered Heart Tissues (rEHTs) as a new model which recapitulates in part the in vivo response after myocardial injury of neonatal and adult heart. When we subjected to cryoinjury immature and mature rEHTs, we observed a significant increase in cardiomyocyte (CM) DNA synthesis when compared to the controls. As expected, the number of mitotic CMs significantly increases in immature rEHTs when compared to mature rEHTs, suggesting that the extent of CM maturation plays a crucial role in their proliferative response after cryoinjury. Moreover, we show that cryoinjury induces a temporary activation of fibroblast response in mature EHTs, similar to the early response after MI, that is however incomplete in immature EHTs. Our results support the hypothesis that the endogenous maturation program in cardiac myocytes plays a major role in determining the proliferative response to injury. Therefore, we propose rEHTs as a robust, novel tool to in vitro investigate critical aspects of cardiac regeneration in a tissue-like asset free from confounding factors in response to injury, such as the immune system response or circulating inflammatory cytokines., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objectives: Although sacral colpopexy is considered the gold standard for the treatment of advanced apical prolapse, several warnings and restrictions has been delivered to urogynecological surgeons in order to avoid the implants of prosthetics meshes. The purpose of this systematic review is to investigate the role of sacral colpopexy performed with autologous tissue in literature., Methods: a systematic review according to PRISMA guidelines was performed in June 2022 through the Medline, Web of Science and Scopus databases. Quality assessment of each article was performed according to Critical Appraisal tool of Oxford center for EBM, LoE according to SORT standards, ROBINS-I tool for methodological assessment in non-randomized trials. From 236 screened records, 7 articles were considered eligible for this systematic review., Results: Collected data showed objective cure rate ranging from 94.7% to 100% in medium term follow up. Subjective cure rate was specifically investigated in 2 studies with high satisfaction rates. Complication rate ranged from 0 to 36.8%, with 90.1% graded ≤2 according to Clavien-Dindo classification., Conclusions: sacral colpopexy with autologous fascia shows satisfying outcomes in terms of safety and efficacy and may be taken in account in particular clinical situations., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Cardiovascular diseases (CVDs), such as arterial hypertension, myocardial infarction, stroke, heart failure, atrial fibrillation, etc., still represent the main cause of morbidity and mortality worldwide. They significantly modify the patients' quality of life with a tremendous economic impact. It is well established that cardiovascular risk factors increase the probability of fatal and non-fatal cardiac events. These risk factors are classified into modifiable (smoking, arterial hypertension, hypercholesterolemia, low HDL cholesterol, diabetes, excessive alcohol consumption, high-fat and high-calorie diet, reduced physical activity) and non-modifiable (sex, age, family history, of previous cardiovascular disease). Hence, CVD prevention is based on early identification and management of modifiable risk factors whose impact on the CV outcome is now performed by the use of CV risk assessment models, such as the Framingham Risk Score, Pooled Cohort Equations, or the SCORE2. However, in recent years, emerging, non-traditional factors (metabolic and non-metabolic) seem to significantly affect this assessment. In this article, we aim at defining these emerging factors and describe the potential mechanisms by which they might contribute to the development of CVD.

The COVID-19 pandemic may have had an impact on healthcare-associated infection (HAI) rates. In this study, we analyzed the occurrence of HAIs in a neonatal intensive care unit (NICU) of the Umberto I teaching hospital in Rome before and during the pandemic. All infants admitted from 1 March 2018 to 28 February 2022 were included and were divided into four groups according to their admission date: two groups before the pandemic (periods I and II) and two during the pandemic (periods III and IV). The association between risk factors and time-to-first event was analyzed using a multivariable Cox regression model. Over the four-year period, a total of 503 infants were included, and 36 infections were recorded. After adjusting for mechanical ventilation, birth weight, sex, type of delivery, respiratory distress syndrome, and previous use of netilmicin and fluconazole, the multivariable analysis confirmed that being hospitalized during the pandemic periods (III and IV) was the main risk factor for HAI acquisition. Furthermore, a change in the etiology of these infections was observed across the study periods. Together, these findings suggest that patient management during the pandemic was suboptimal and that HAI surveillance protocols should be implemented in the NICU setting promptly.

The abdominal aortic aneurysm (AAA) is a potentially fatal asymptomatic disease. It progresses silently with clinical complications that, when they occur, constitute a very serious event, frequently resulting in the patient's exitus. As a result, early detection and treatment are critical because the right therapeutic strategy can halt the disease's natural progression. AAA is frequently discovered as an incidental finding during an abdominal ultrasound or a plain X-ray of the abdomen, which is required for other pathologies. The primary diagnostic tool for AAA identification is abdominal B-mode ultrasound. It is cheap, widely available, non-invasive, and has high diagnostic sensitivity. However, this diagnostic tool may fail in rare cases due to misleading anatomical findings. We present an unusual flaw in the echographic AAA evaluation that should be considered during the diagnostic work-up.

Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20-25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients' management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management.

This article explores the territorial differences in the onset and spread of COVID-19 and the excess mortality associated with the pandemic, with a focus on European regions and US counties. Both in Europe and in the US, the pandemic arrived earlier and recorded higher Rt values in urban regions than in intermediate and rural ones. A similar gap is also found in the data on excess mortality. In the weeks during the first phase of the pandemic, urban regions in EU countries experienced excess mortality of up to 68 pp more than rural ones. We show that, during the initial days of the pandemic, territorial differences in Rt by the degree of urbanisation can be largely explained by the level of internal, inbound and outbound mobility. The differences in the spread of COVID-19 by rural-urban typology and the role of mobility are less clear during the second wave. This could be linked to the fact that the infection is widespread across territories, to changes in mobility patterns during the summer period as well as to the different containment measures which reverse the link between mobility and Rt., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Natale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.

Maternal overnutrition has been reported to affect brain plasticity of the offspring by altering gene expression, regulating both synaptic plasticity and adult neurogenesis. However, whether perinatal metabolic stress may influence the accumulation of misfolded proteins and the development of neurodegeneration remains to be clarified. We investigated the impact of maternal high fat diet (HFD) in an experimental model of Alzheimer's disease (AD). The 3xTg-AD mice born to overfed mothers showed an impairment of synaptic plasticity and cognitive deficits earlier than controls. Maternal HFD also altered the expression of genes regulating amyloid-β-protein (Aβ) metabolism (i.e., Bace1, Ern1, Ide and Nicastrin) and enhanced Aβ deposition in the hippocampus. Finally, we found an epigenetic derangement and an aberrant recruitment of transcription factors NF-kB and STAT3 and chromatin remodeler HDAC2 on the regulatory sequences of the same genes. Collectively, our data indicate that early life metabolic stress worsens the AD phenotype via epigenetic alteration of genes regulating Aβ synthesis and clearance.

Introduction: Bladder pain syndrome/interstitial cystitis (BPS/IC) is either Hunner lesion interstitial cystitis (HL IC) or non-Hunner lesion interstitial cystitis (N-HL IC), differing in the presence of HLs on cystoscopy. Cystoscopy is essential in diagnosing HL but are bladder biopsies useful in N-HL IC patients? Our objective was to assess bladder biopsy in patients with N-HL IC, evaluating whether the count of mast cells (MCs) and percentage of activated MCs could measure severity., Materials and Methods: This is a single-centre retrospective study., Inclusion Criteria: diagnosis of BPS/IC by ESSIC definition; absence of HLs. Each patient had three bladder biopsies., Statistical Analysis: χ2/Fischer's exact test; Wilcoxon signed-ranks test/Mann-Whitney U test. Statistical significance: p < 0.05., Results: We separated 48 women into Group 1 with <50% of MCs activated and Group 2 with >50%. We compared the results of the O'Leary-Sant questionnaire between the two groups and did not find any correlation between the severity of the pathology and either the MC count in the detrusor or the percentage of activated MCs in the lamina propria or detrusor., Discussion/conclusion: These findings cast doubt on the usefulness of bladder biopsy for the evaluation of severity in N-HL IC., (© 2022 S. Karger AG, Basel.)

Competing Interests: There are no conflicts of interest.

Background: Approximately 85-90% of congenital cytomegalovirus infections (cCMV) are asymptomatic. Few studies have investigated early and long-term neurodevelopmental outcomes in children with asymptomatic cCMV (acCMV), and the data is contradictory. In the present study, we did investigate the effect of cCMV asymptomatic infection on neurological outcomes and in cognitive, language and motor development at 6 months of age., Methods: Fifty-six children with cCMV asymptomatic infection were followed for 6 months, as part of a long-term surveillance program, examining their neurological and developmental outcomes. Neurological examination and Bayley-III Scales were performed., Results: Clinical evaluation revealed that early neurological outcomes were essentially normal, with minor neurological deficits (i.e., tone abnormalities) in a subgroup of patients. Bayley-III scores were substantially in the normal range, with 14% showing a score less than 85 (-1SD) in the Motor Scale. Children's neurological and neurodevelopmental outcomes at 6 months of age did not differ according to the trimester of infection., Conclusions: Some infants with cCMV asymptomatic infection may present minor neurological abnormalities in early stages of life. It seems useful to monitor this population for early and late neurodevelopmental sequelae., (© 2022. The Author(s).)

Neurodegenerative disorders are one of the most common causes of disability and represent 6.3% of the global burden of disease. Among them, Alzheimer's, Parkinson's, and Huntington's diseases cause cognitive decline, representing the most disabling symptom on both personal and social levels. The molecular mechanisms underlying the onset and progression of dementia are still poorly understood, and include secretory factors potentially affecting differentiated neurons, glial cells and neural stem cell niche. In the last decade, much attention has been devoted to exosomes as novel carriers of information exchanged among both neighbouring and distant cells. These vesicles can be generated and internalized by different brain cells including neurons, neural stem cells, astrocytes, and microglia, thereby affecting neural plasticity and cognitive functions in physiological and pathological conditions. Here, we review data on the roles of exosomes as carriers of bioactive molecules potentially involved in the pathogenesis of neurodegenerative disorders and detectable in biological fluids as biomarkers of dementia. We also discuss the experimental evidence of the therapeutic potential of stem cell-derived vesicles in experimental models of neurodegeneration-dependent cognitive decline., (© 2022. The Author(s).)

Competing Interests: Conflict of interest: None declared.

Competing Interests: There are no conflicts of interest.

Thanks to an unusual reversible cause of reflex syncope, a young physician avoided pacemaker implantation. We present the treatment of a bizarre case of gastro-cardiac syndrome, an often-overlooked clinical entity.

Early-life metabolic stress has been demonstrated to affect brain development, persistently influence brain plasticity and to exert multigenerational effects on cognitive functions. However, the impact of an ancestor's diet on the adult neurogenesis of their descendants has not yet been investigated. Here, we studied the effects of maternal high fat diet (HFD) on hippocampal adult neurogenesis and the proliferation of neural stem and progenitor cells (NSPCs) derived from the hippocampus of both the second and the third generations of progeny (F2 HFD and F3 HFD ). Maternal HFD caused a multigenerational depletion of neurogenic niche in F2 HFD and F3 HFD mice. Moreover, NSPCs derived from HFD descendants showed altered expression of genes regulating stem cell proliferation and neurodifferentiation (i.e., Hes1, NeuroD1, Bdnf). Finally, ancestor HFD-related hyper-activation of both STAT3 and STAT5 induced enhancement of their binding on the regulatory sequences of Gfap gene and an epigenetic switch from permissive to repressive chromatin on the promoter of the NeuroD1 gene. Collectively, our data indicate that maternal HFD multigenerationally affects hippocampal adult neurogenesis via an epigenetic derangement of pro-neurogenic gene expression in NSPCs.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus., Methods: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity., Results: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection., Conclusions: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit., Competing Interests: Potential conflicts of interest . V. P. participated in a lecture on coronavirus disease 2019 vaccination in children (with honorarium made to their university), and also participated in the National Greek Advisory Committee for Immunization Practices. C. P. was a steering committee member for clinical trials MN42988 and MN42989 by La Roche Ltd. A. A. received an National Institute of Allergy and Infectious Diseases (NIAID) Development of Sample Sparing Assays (DSSA) for Monitoring Immune Responses Infrastructure & Opportunity Fund (IOF) Award grant for Comprehensive Analysis of the Neonatal Immune System via High-Throughout Proteomics; and honorarium for an invited review article on neonatal vaccination. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite being a crucial physiological function of the brain, the mechanisms underlying forgetting are still poorly understood. Estrogens play a critical role in different brain functions, including memory. However, the effects of sex hormones on forgetting vulnerabilitymediated by retroactive interference (RI), a phenomenon in which newly acquired information interferes with the retrieval of already stored information, are still poorly understood. The aim of our study was to characterize the sex differences in interference-mediated forgetting and identify the underlying molecular mechanisms. We found that adult male C57bl/6 mice showed a higher susceptibility to RI-dependent memory loss than females. The preference index (PI) in the NOR paradigm was 52.7 ± 5.9% in males and 62.3 ± 13.0% in females. The resistance to RI in female mice was mediated by estrogen signaling involving estrogen receptor α activation in the dorsal hippocampus. Accordingly, following RI, females showed higher phosphorylation levels (+30%) of extracellular signal-regulated kinase1/2 (ERK1/2) in the hippocampus. Pharmacological inhibition of ERK1/2 made female mice prone to RI. The PI was 70.6 ± 11.0% in vehicle-injected mice and 47.4 ± 10.8% following PD98059 administration. Collectively, our data suggest that hippocampal estrogen α receptor-ERK1/2 signaling is critically involved in a pattern separation mechanism that inhibits object-related RI in female mice.

Neural stem and progenitor cell (NSPC) depletion may play a crucial role in the cognitive impairment observed in many age-related non-communicable diseases. Insulin resistance affects brain functions through a plethora of mechanisms that remain poorly understood. In an experimental model of insulin resistant NSPCs, we identified a novel molecular circuit relying on insulin receptor substrate-1 (IRS-1)/ Forkhead box O (FoxO) signaling cascade and inhibiting the recruitment of transcription factors FoxO1 and FoxO3a on the promoters of genes regulating proliferation and self-renewal. Insulin resistance also epigenetically increased the expression of cyclin-dependent kinase inhibitor 1 (p21) and accelerated NSPC senescence. Of note, we found that stimulation of NSPCs with NSPC-derived exosomes (exo-NSPC) rescued IRS-1/FoxO activation and counteracted both the reduced proliferation and senescence of stem cells. Accordingly, intranasal administration of exo-NSPC counteracted the high-fat diet-dependent impairment of adult hippocampal neurogenesis in mice by restoring the balance between proliferating and senescent NSPCs in the hippocampus. Our findings suggest a novel mechanism underlying the metabolic control of NSPC fate potentially involved in the detrimental effects of metabolic disorders on brain plasticity. In addition, our data highlight the role of extracellular vesicle-mediated signals in the regulation of cell fate within the adult neurogenic niche., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)