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Salivary glands’ neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.

Neurological disorders such as stroke, Parkinson’s disease (PD), and severe traumatic brain injury (sTBI) are leading global causes of disability and mortality. This study aimed to assess the ability to walk of patients with sTBI, stroke, and PD, identifying the differences in dynamic postural stability, symmetry, and smoothness during various dynamic motor tasks. Sixty people with neurological disorders and 20 healthy participants were recruited. Inertial measurement unit (IMU) sensors were employed to measure spatiotemporal parameters and gait quality indices during different motor tasks. The Mini-BESTest, Berg Balance Scale, and Dynamic Gait Index Scoring were also used to evaluate balance and gait. People with stroke exhibited the most compromised biomechanical patterns, with lower walking speed, increased stride duration, and decreased stride frequency. They also showed higher upper body instability and greater variability in gait stability indices, as well as less gait symmetry and smoothness. PD and sTBI patients displayed significantly different temporal parameters and differences in stability parameters only at the pelvis level and in the smoothness index during both linear and curved paths. This study provides a biomechanical characterization of dynamic stability, symmetry, and smoothness in people with stroke, sTBI, and PD using an IMU-based ecological assessment.

Musculoskeletal symptoms are common in both acute COVID-19 disease and post-acute sequelae (Post-Acute COVID Syndrome). The purpose of this study is to investigate whether there are reduced levels of masticatory function in patients with PACS (Post Acute COVID Syndrome) who suffer from sarcopenia, under the hypothesis that the latter may also involve the masticatory muscles. This study includes 23 patients hospitalized for COVID-19 between February 2020 and April 2021 and currently suffering from PACS. Among these PACS patients, 13/23 (56%) suffer from sarcopenia, 5/23 (22%) complain of asthenia but do not suffer from sarcopenia and the remaining 5/23 (22%) do not present muscle symptoms (non-asthenic non-sarcopenic). Oral health indices of all patients were collected. The masticatory strength was assessed with a gnathodynamometer based on piezoresistive sensors, and the masticatory effectiveness was measured by administering the “chewing gum mixing ability test” by having patients perform 20 masticatory cycles on a two-color chewing gum and analyzing the outcome through the ViewGum© software. Moreover, we gathered data with a hand grip test and gait speed test. The data collected in this study show that PACS sarcopenic patients have decreased masticatory effectiveness and strength compared to PACS asthenic non-sarcopenic patients and PACS non-asthenic non-sarcopenic patients.

Post-harvest decay of fresh table grapes causes considerable annual production losses. The main fungal agents of decay both in pre- and post-harvest are B. cinerea, Penicillium spp., Aspergillus spp., Alternaria spp., and Cladosporium spp. To date, the use of agrochemicals and SO2 are the main methods to control grape molds in pre- and postharvest, respectively. Significant improvements, however, have already been made in to apply innovative and more environmentally sustainable control strategies, such as Biological Control Agents (BCAs), which can reduce disease severity in both pre- and post-harvest. In this study, 31 new non-Saccharomyces yeast strains, isolated from berries of native Apulian table grape genotypes, were tested for their in vivo effectiveness against grey mold of table grapes, resulting in two St. bacillaris (‘N22_I1’ and ‘S13_I3’), one S. diversa (‘N22_I3’), one A. pullulans (‘OLB_9.1_VL’) and one H. uvarum (‘OLB_9.1_BR’) yeast strains that were marked as efficient and good BCAs. Their mechanisms of action were characterized through in vitro assays, and additional characteristics were evaluated to assess the economic feasibility and viability for future technological employment. Their effectiveness was tested by reducing the working concentration, their antagonistic effect on a wide range of fungal pathogens, their ability to survive in formulations with long shelf life, and their safety to human health.

The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.

Background: Vulvar dermatofibrosarcoma protuberans is an extremely rare disease. Its rarity can hamper the quality of treatment; deeper knowledge is necessary to plan appropriate management. The purpose of this review is to analyse the data reported in the literature to obtain evidence regarding appropriate disease management. Methods: We made a systematic search of the literature, including the terms “dermatofibrosarcoma protuberans”, “vulva”, and “vulvar”, alone or in combination. We selected articles published in English from two electronic databases, PubMed and MEDLINE, and we analysed their reference lists to include other potentially relevant studies. Results: We selected 39 articles, with a total of 68 cases reported; they were retrospective case reports and case series. Dermatofibrosarcoma protuberans of the vulva tends towards local recurrence; an early and timely pathological diagnosis, together with an appropriate surgical approach, are of utmost importance to ensure free margins and maximise the curative potential. Conclusions: Even if this is an indolent disease and it generally shows a good prognosis, appropriate management may help in reducing the rate of local recurrences that may hamper patients’ quality of life. Management by a multidisciplinary team is highly recommended.

Limosilactobacillus fermentum Lf2 (Lf2) is an autochthonous strain that produces high levels of exopolysaccharides (EPS). The objective of this work was to evaluate the probiotic potential of Lf2 and its relationship with these metabolites in a mouse model of TNBS (trinitrobenzene sulfonic acid)-induced chronic colitis. Mice were treated intrarectally with increasing doses of TNBS resuspended in 50% ethanol for 14 days. In parallel, they received different treatments by gavage (lactose 10% as the matrix): freeze-dried Lf2 (L); purified EPS (E); and lactose 10% (T). A healthy control group (H) was treated with 50% alcohol without TNBS (intrarectally) and 10% lactose (by gavage). In the small intestine, there was a significant increase in IgA levels for the group that received EPS and a decrease in IFN-γ for mice treated with the strain compared to the other groups. In the large intestine, IL-2 and IFN-γ presented the lowest levels in the groups treated with EPS and the strain. The concentrations of acetic and propionic acids in mice that received Lf2 were the highest, while the levels of butyric acid were comparable to the healthy control group. An increase in the abundance of SCFA-producing bacteria was observed for mice treated with EPS and the strain in comparison with the colitis control group. The enzyme activity of catalase was higher in all the treatments compared to the TNBS-induced colitis control mice. To summarize the results obtained, a principal component analysis (PCA) was performed, clearly grouping the treatments in different clusters according to the variables studied. This is one of the first studies to address the role of a potential probiotic strain in a chronic colitis mouse model, trying to elucidate the relationship between its properties and the EPS synthesized.

The demand for sustainable cosmetics leads to the search for natural and biotechnological ingredients. The present study reports the development of a multifunctional lip moisturizer containing levan (LEV) from Bacillus subtilis natto, sophorolipids (SOPs) from Starmerella bombicola and Citrus paradisi (OCP) essential oil, using a simplex-centroid experimental design. The formulations were evaluated physicochemically, pharmacotechnically and by DPPH assay. The optimized formulation was selected through the Response Surface Method, and the evaluation of its efficiency in lip hydration was carried out using the bioimpedance method and sensory analysis. The formulations showed pH compatibility with lips and remained stable after a centrifuge test and thermal stress. Spreadability varied between 415.3 and 1217.1 mm2, moisture retention was above 95% and antioxidant capacity was around 50% for all formulations. The optimized formulation, containing 0.4% LEV and 0.8% SOF, maintained the lip hydration already shown by the participants; 85% of them reported improvement in this aspect. For the first time, LEV and SOP were incorporated in lip moisturizers, which is an environmentally friendly product with marketing potential. Furthermore, the use of the Skin Analyzer Digital equipment, a low-cost and non-invasive technique, to evaluate the effectiveness of lip products is innovative; this methodology may help in the development of future cosmetology studies.

Objective: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. Methodology: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group. Results: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10–12) in the control group vs. 8 months (95% IC 6–9) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28–5.06) for the case group (p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand–foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented. Conclusion: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.

Veterinarians, unlike human physicians, could potentially care for the patient for several years, from conception to end-of-life care. Because of their close relationship with the animal, healthcare providers (for example, veterinarians and staff) are more likely to be affected by bad events and end-of-life care. The purpose of this study was to assess the emotional impact of patients’ deaths on Brazilian veterinarians; 549 Brazilian veterinarians (78.3% females) completed a 20-item online questionnaire. Females were more emotionally affected than males by having to talk to the owner about their animal’s death and more emotionally affected by the animal’s death itself. Furthermore, the emotional impact of an animal’s death was heavily influenced by the number of animals euthanized and varied greatly across veterinarians based on their age, with vets over 50 years old being less affected than vets between the ages of 31 and 40. The majority of responders (91.0%) were not trained to deal with grief during their degree. Those who had some training reported being less affected by bereavement. These findings indicate that patient death is a significant emotional concern for veterinarians. Specific education during the degree course, aimed at preparing future veterinarians to deal with death and death communication, is lacking but necessary.

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51–0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early.

We analyze schemes of high-fidelity multi-qubit CNOTN and C2NOT2 gates for alkali metal neutral atoms used as qubits. These schemes are based on the electromagnetically induced transparency and Rydberg blockade. The fidelity of homonuclear multi-qubit CNOTN gate based on Rydberg blockade was limited by the undesirable interaction between the target atoms and by the coupling laser intensity. We propose overcoming these limits by using strong heteronuclear dipole–dipole interactions via Förster resonances for control and target atoms, while the target atoms are coupled by a weaker van der Waals interaction. We optimized the gate performance in order to achieve higher fidelity, while keeping the coupling laser intensity as small as possible in order to improve the experimental feasibility of the gate schemes. We also considered the optimization of the schemes of the C2NOT2 gates, where the fidelity is affected by the relation between the control–control, control–target and target–target interaction energies. Our numeric simulations confirm that the fidelity of the CNOT4 gate (single control and four target atoms) can be up to 99.3% and the fidelity of the C2NOT2 (two control and two target atoms) is up to 99.7% for the conditions which are experimentally feasible.

Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.

γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a flavoring agent in food and beverage manufacturing. In this research, the biological efficacy of γ-terpinene, α-terpinene, p-cymene, and myrcene was studied in human cell lines (HeLa, SH-SY5Y, and HDFa). Cytotoxicity, cell proliferation, cell migration, and morphology assays were performed to obtain detailed information on the anticancer properties. Our results show that myrcene has potential biological activity, especially in HeLa cells. In this cell line, it leads to an arrest of proliferation, a decrease in motility and morphological changes with loss of sphericity and thickness, and DNA damage. In addition, the interaction of γ-terpinene, α-terpinene, p-terpinene, and myrcene with calf thymus DNA (ct-DNA) was studied by UV-visible spectrophotometry. DNA binding experiments show that only myrcene can interact with DNA with an apparent dissociation constant (Kd) of 29 × 10−6 M.

Asthma is the most frequent chronic disease of childhood, affecting up to 20% of children worldwide. The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment. This project aims to summarize the most recent evidence regarding maintenance therapy for asthma in children and adolescents. A multidisciplinary panel of experts was asked clinical questions regarding the treatment of children and adolescents with asthma. Overall, 10 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results showed that the choice of medication depends on the severity of the child’s asthma, phenotype, age, preference, and individual factors. In addition to medications, the identification of comorbidities and modifiable factors is crucial to obtaining good control. Asthma in children is heterogeneous, and its evolution varies over time. Since most recommendations for asthma management in childhood are extrapolated from clinical studies performed in adults, more clinical trials specifically designed for young children should be conducted.

The Corning Epic® label-free (ELF) system is an innovative technology widely used in drug discovery, immunotherapy, G-protein-associated studies, and biocompatibility tests. Here, we challenge the use of ELF to further investigate the biocompatibility of resins used in manufacturing of blood filters, a category of medical devices representing life-saving therapies for the increasing number of patients with kidney failure. The biocompatibility assays were carried out by developing a cell model aimed at mimicking the clinical use of the blood filters and complementing the existing cytotoxicity assay requested by ISO10993-5. Experiments were performed by putting fibroblasts in both direct contact with two types of selected resins, and indirect contact by means of homemade customized well inserts that were precisely designed and developed for this technology. For both types of contact, fibroblasts were cultured in medium and human plasma. ELF tests confirmed the biocompatibility of both resins, highlighting a statistically significant different biological behavior of a polyaromatic resin compared to control and ion-exchanged resin, when materials were in indirect contact and soaking with plasma. Overall, the ELF test is able to mimic clinical scenarios and represents a promising approach to investigate biocompatibility, showing peculiar biological behaviors and suggesting the activation of specific intracellular pathways.

After amputation, granular hemocytes infiltrate the blastema of regenerating cephalic tentacles of the freshwater snail Pomacea canaliculata. Here, the circulating phagocytic hemocytes were chemically depleted by injecting the snails with clodronate liposomes, and the effects on the cephalic tentacle regeneration onset and on Pc-Hemocyanin, Pc-transglutaminase (Pc-TG) and Pc-Allograft Inflammatory Factor-1 (Pc-AIF-1) gene expressions were investigated. Flow cytometry analysis demonstrated that clodronate liposomes targeted large circulating hemocytes, resulting in a transient decrease in their number. Corresponding with the phagocyte depletion, tentacle regeneration onset was halted, and it resumed at the expected pace when clodronate liposome effects were no longer visible. In addition to the regeneration progress, the expressions of Pc-Hemocyanin, Pc-TG, and Pc-AIF-1, which are markers of hemocyte-mediated functions like oxygen transport and immunity, clotting, and inflammation, were modified. After the injection of clodronate liposomes, a specific computer-assisted image analysis protocol still evidenced the presence of granular hemocytes in the tentacle blastema. This is consistent with reports indicating the large and agranular hemocyte population as the most represented among the professional phagocytes of P. canaliculata and with the hypothesis that different hemocyte morphologies could exert diverse biological functions, as it has been observed in other invertebrates.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27– patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51– patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Evidence indicates that different pathways of malignant degeneration underlie the development of endometriosis-associated ovarian tumors of endometrioid and clear cell histotypes. The aim of this study was to compare data from patients affected by these two histotypes to investigate the hypothesis of a dichotomy in the histogenesis of these tumors. Clinical data and tumor characteristics of 48 patients who were diagnosed with either pure clear cell ovarian cancer and mixed endometrioid–clear cell ovarian cancer arising from endometriosis (ECC, n = 22) or endometriosis-associated endometrioid ovarian cancer (EAEOC, n = 26) were compared. A previous diagnosis of endometriosis was detected more frequently in the ECC group (32% vs. 4%, p = 0.01). The incidence of bilaterality was significantly higher in the EAOEC group (35% vs. 5%, p = 0.01) as well as a solid/cystic rate at gross pathology (57.7 ± 7.9% vs. 30.9 ± 7.5%, p = 0.02). Patients with ECC had a more advanced disease stage (41% vs. 15%; p = 0.04). A synchronous endometrial carcinoma was detected in 38% of EAEOC patients. A comparison of the International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis showed a significantly decreasing trend for ECC compared to EAEOC (p = 0.02). These findings support the hypothesis that the origin, clinical behavior and relationship with endometriosis might be different for these histotypes. ECC, unlike EAEOC, seems to develop within an endometriotic cyst, thus representing a window of possibility for ultrasound-based early diagnosis.

Nowadays, in the case of suspected prostate cancer (PCa), tissue needle biopsy remains the benchmark for diagnosis despite its invasiveness and poor tolerability, as serum prostate-specific antigen (PSA) is limited by low specificity. The aim of this proteomic study was to identify new diagnostic biomarkers in urine, an easily and non-invasively available sample, able to selectively discriminate cancer from benign prostatic hyperplasia (BPH), evaluating whether the presence of inflammation may be a confounding parameter. The analysis was performed by two-dimensional gel electrophoresis (2-DE), mass spectrometry (LC-MS/MS) and Enzyme-Linked Immunosorbent Assay (ELISA) on urine samples from PCa and BPH patients, divided into subgroups based on the presence or absence of inflammation. Significant quantitative and qualitative differences were found in the urinary proteomic profile of PCa and BPH groups. Of the nine differentially expressed proteins, only five can properly be considered potential biomarkers of PCa able to discriminate the two diseases, as they were not affected by the inflammatory process. Therefore, the proteomic research of novel and reliable urinary biomarkers of PCa should be conducted considering the presence of inflammation as a realistic interfering element, as it could hinder the detection of important protein targets.

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/− female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/− mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/− hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

The olfactory bulb (OB) is one of two regions of the mammalian brain which undergo continuous neuronal replacement during adulthood. A significant fraction of the cells added in adulthood to the bulbar circuitry is constituted by dopaminergic (DA) neurons. We took advantage of a peculiar property of dopaminergic neurons in transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter: while DA neurons located in the glomerular layer (GL) display full electrophysiological maturation, eGFP+ cells in the mitral layer (ML) show characteristics of immature cells. In addition, they also display a lower fluorescence intensity, possibly reflecting different degrees of maturation. To investigate whether this difference in maturation might be confirmed at the gene expression level, we used a fluorescence-activated cell sorting technique on enzymatically dissociated cells of the OB. The cells were divided into two groups based on their level of fluorescence, possibly corresponding to immature ML cells and fully mature DA neurons from the GL. Semiquantitative real-time PCR was performed to detect the level of expression of genes linked to the degree of maturation of DA neurons. We showed that indeed the cells expressing low eGFP fluorescence are immature neurons. Our method can be further used to explore the differences between these two groups of DA neurons.

Purpose: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent 18F-FDG PET (2009–2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80–20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. Results: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. Conclusions: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients.

Current technologies based on inertial measurement units (IMUs) are considered valid and reliable tools for monitoring barbell velocity in strength training. However, the extracted outcomes are often limited to a few velocity metrics, such as mean or maximal velocity. This study aimed at validating a single IMU-based methodology to automatically obtain the barbell velocity full profile as well as key performance metrics during maximal Paralympic bench press. Seven Paralympic powerlifters (age: 30.5 ± 4.3 years, sitting height: 71.6 ± 6.8 cm, body mass: 72.5 ± 16.4 kg, one-repetition maximum: 148.4 ± 38.6 kg) performed four attempts of maximal Paralympic bench press. The barbell velocity profile and relevant metrics were automatically obtained from IMU linear acceleration through a custom-made algorithm and validated against a video-based reference system. The mean difference between devices was 0.00 ± 0.04 m·s−1 with low limits of agreement (−1) and moderate-to-good reliability (ICC: 0.55–0.90). Linear regression analysis showed large-to-very large associations between paired measurements (r: 0.57–0.91, p < 0.003; SEE: 0.02–0.06 m·s−1). The analysis of velocity curves showed a high spatial similarity and small differences between devices. The proposed methodology provided a good level of agreement, making it suitable for different applications in barbell velocity monitoring during maximal Paralympic bench press.

Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006–2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young: p = 0.395). Conclusions. Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor.

Since the multifunctionality of transglutaminase 2 (TG2) includes extra- and intracellular functions, we investigated the effects of intracellular administration of TG2 inhibitors in three breast cancer cell lines, MDA-MB-231, MDA-MB-436 and MDA-MB-468, which are representative of different triple-negative phenotypes, using a patch-clamp technique. The first cell line has a highly voltage-dependent a membrane current, which is low in the second and almost absent in the third one. While applying a voltage protocol to responsive single cells, injection of TG2 inhibitors triggered a significant decrease of the current in MDA-MB-231 that we attributed to voltage-dependent K+ channels using the specific inhibitors 4-aminopyridine and astemizole. Since the Kv10.1 channel plays a dominant role as a marker of cell migration and survival in breast cancer, we investigated its relationship with TG2 by immunoprecipitation. Our data reveal their physical interaction affects membrane currents in MDA-MB-231 but not in the less sensitive MDA-MB-436 cells. We further correlated the efficacy of TG2 inhibition with metabolic changes in the supernatants of treated cells, resulting in increased concentration of methyl- and dimethylamines, representing possible response markers. In conclusion, our findings highlight the interference of TG2 inhibitors with the Kv10.1 channel as a potential therapeutic tool depending on the specific features of cancer cells.

Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic BRCA variants, but also BRCAwt/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad’s. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of PTEN and EMSY. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing.

Astaxanthin is a red orange xanthophyll carotenoid produced mainly by microalgae but which can also be chemically synthesized. As demonstrated by several studies, this lipophilic molecule is endowed with potent antioxidant properties and is able to modulate biological functions. Unlike synthetic astaxanthin, natural astaxanthin (NAst) is considered safe for human nutrition, and its production is considered eco-friendly. The antioxidant activity of astaxanthin depends on its bioavailability, which, in turn, is related to its hydrophobicity. In this study, we analyzed the water-solubility of NAst and assessed its protective effect against oxidative stress by means of different approaches using a neuroblastoma cell model. Moreover, due to its highly lipophilic nature, astaxanthin is particularly protective against lipid peroxidation; therefore, the role of NAst in counteracting ferroptosis was investigated. This recently discovered process of programmed cell death is indeed characterized by iron-dependent lipid peroxidation and seems to be linked to the onset and development of oxidative-stress-related diseases. The promising results of this study, together with the “green sources” from which astaxanthin could derive, suggest a potential role for NAst in the prevention and co-treatment of chronic degenerative diseases by means of a sustainable approach.

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children’s exposure to risk factors that may permanently affect respiratory health.

Neurorehabilitation research in patients with traumatic brain injury (TBI) showed how vestibular rehabilitation (VR) treatments positively affect concussion-related symptoms, but no studies have been carried out in patients with severe TBI (sTBI) during post-acute intensive neurorehabilitation. We aimed at testing this effect by combining sensor-based gait analysis and clinical scales assessment. We hypothesized that integrating VR in post-acute neurorehabilitation training might improve gait quality and activity of daily living (ADL) in sTBI patients. A two-arm, single-blind randomized controlled trial with 8 weeks of follow-up was performed including thirty sTBI inpatients that underwent an 8-week rehabilitation program including either a VR or a conventional program. Gait quality parameters were obtained using body-mounted magneto-inertial sensors during instrumented linear and curvilinear walking tests. A 4X2 mixed model ANOVA was used to investigate session–group interactions and main effects. Patients undergoing VR exhibited improvements in ADL, showing early improvements in clinical scores. Sensor-based assessment of curvilinear pathways highlighted significant VR-related improvements in gait smoothness over time (p < 0.05), whereas both treatments exhibited distinct improvements in gait quality. Integrating VR in conventional neurorehabilitation is a suitable strategy to improve gait smoothness and ADL in sTBI patients. Instrumented protocols are further promoted as an additional measure to quantify the efficacy of neurorehabilitation treatments.

The development of immunosensors to detect antibodies or antigens has stood out in the face of traditional methods for diagnosing emerging diseases such as the one caused by the SARS-CoV-2 virus. The present study reports the construction of a simplified electrochemical immunosensor using a graphene-binding peptide applied as a recognition site to detect SARS-CoV-2 antibodies. A screen-printed electrode was used for sensor preparation by adding a solution of peptide and reduced graphene oxide (rGO). The peptide-rGO suspension was characterized by scanning electron microscopy (SEM), Raman spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). The electrochemical characterization (electrochemical impedance spectroscopy—EIS, cyclic voltammetry—CV and differential pulse voltammetry—DPV) was performed on the modified electrode. The immunosensor response is based on the decrease in the faradaic signal of an electrochemical probe resulting from immunocomplex formation. Using the best set of experimental conditions, the analytic curve obtained showed a good linear regression (r2 = 0.913) and a limit of detection (LOD) of 0.77 μg mL−1 for antibody detection. The CV and EIS results proved the efficiency of device assembly. The high selectivity of the platform, which can be attributed to the peptide, was demonstrated by the decrease in the current percentage for samples with antibody against the SARS-CoV-2 S protein and the increase in the other antibodies tested. Additionally, the DPV measurements showed a clearly distinguishable response in assays against human serum samples, with sera with a response above 95% being considered negative, whereas responses below this value were considered positive. The diagnostic platform developed with specific peptides is promising and has the potential for application in the diagnosis of other infections that lead to high antibody titers.

The protection of wetlands is a cornerstone in the conservation of pond-breeding amphibians. Because protected wetlands are rarely natural areas, but are often man-made, at least in Europe, it is important that they are well managed to fulfill their intended function. Appropriate management requires knowledge of the ecology of the species, particularly habitat requirements. Here, we combine species monitoring data and habitat mapping data in an analysis where our goal was to describe the factors that determine the occupancy of amphibian species in federally protected amphibian breeding sites. As expected, every species had its own habitat requirements, often a combination of both a terrestrial and aquatic habitat (i.e., landscape complementation). In most species, occupancy was strongly positively affected with the amount of aquatic habitat, but predicted occupancy probabilities were low because the amount of aquatic habitat was low in most sites. The area or proportion of ruderal vegetation also had positive effects on multiple species, while other types of terrestrial habitat (e.g., meadows) led to low occupancy probabilities. The total area of the protected breeding sites was never included in a final model and connectivity was important only for one species (Triturus cristatus). The latter finding implies that the quality of the landscape between breeding sizes is more important than distance per se, while the former implies that the area of some specific habitats within breeding sites is crucial for high occupancies. Thus, increasing the amount of aquatic habitats and likewise terrestrial habitats within protected areas would make them more likely to achieve their conservation objectives. Our study is an example of how the joint analysis of monitoring data and habitat data (based on mapping in the field) can lead to evidence-based suggestions on how to improve conservation practice.

Paenibacillus larvae (P. larvae) is responsible for American foulbrood (AFB), the most severe bacterial disease of honeybees. The enumeration of P. larvae spores in substrates taken from hives allows for the identification of the contamination levels of the colonies, mostly in those with atypical symptoms or with asymptomatic infections; in these cases, it is essential for the effective control of American foulbrood (AFB). In this work we described a new quantitative TaqMan® probe-based real-time PCR (qPCR) assay, targeting the 16S rRNA gene of P. larvae, used for the quantification of P. larvae spores in powdered sugar samples collected from hives, in comparison to the culture. A total of 105 colonies were selected, belonging to 10 apiaries with different levels of infection, located in northern Italy. The proportions of positive colonies was 54% (57/105) with the culture and 66% (69/105) with qPCR. A significant difference between the two methods was found with McNemar’s test (p = 0.02). Out of the 51 positive samples by both methods, 45 showed higher infection by qPCR compared to the culture. A close concordance with the clinical–epidemiological status of the hives was observed by both methods, with higher infection levels found by qPCR.

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption.

Anthracnose, caused by fungi of the genus Colletotrichum, is present in the main areas where rubber trees (Hevea brasiliensis) are planted. Thus, considering that biological agents can be an alternative for disease control, the present study aimed to carry out initial studies to investigate the response of rubber tree seedlings inoculated with Colletotrichum and treated with saprobes fungi from the semiarid region of Northeast Brazil (Curvularia eragrostidis, Memnoniella levispora, Myrothecium roridum and Phialomyces macrosporus). Seedlings of the rubber tree clone RRIM600 were sprayed with biocontrol agents as preventive and curative treatments seven days before and after C. tamarilloi inoculation, respectively. Assessments included plant response to disease expression based on the percentage of symptomatic area on treated leaves, percentage of graft death, and percentage of apical death in seedlings 30 days after inoculation with C. tamarilloi. In addition, the enzymes peroxidase and phenylalanine ammonia lyase (PAL) had their activity quantified by their association with plant resistance to pathogens. The fungus C. eragrostidis had the best result in controlling anthracnose when applied as a preventive treatment, showing 10% less disease than the untreated plant. The same was observed for the fungus P. macrosporus when used in the curative form. These fungi also reduced the graft death. In these cases, PAL activity was higher and may be linked to the induction of resistance against the pathogen. The peroxidase activity was not expressive for treatments with saprobic fungi in the periods studied. Therefore, among the tested fungi, C. eragrostidis and P. macrosporus are promising for the control of anthracnose, deserving further studies.

We aimed to investigate the significance of optical coherence tomography (SD-OCT) in managing pediatric optic pathway gliomas (OPGs) in children younger than 5 years of age. A retrospective monocentric study was conducted. SD-OCT scans were obtained using the handheld iVue system to assess peripapillary retinal nerve fibre layer (pRNFL) thickness at three time points: baseline (OCT1), end of treatment (OCT2), and at last follow-up (OCT3). We compared the median value of pRNFL (and interquartile range—IQR) at different follow-up times and in different sub-groups (stable disease—SD, partial response—PR, and progression disease—PD). Thirteen children younger than 5 years of age were included. The Median follow-up time was 3.9 years (IQR 1.2). Six patients showed a pRNFL change of more than 10% during follow-up. Seven patients showed PD during follow-up. Median pRNFL at baseline was 81.5 µm (IQR 31.5); median pRNFL at the end of treatment was 73 µm (IQR 33); median pRNFL at last follow-up was 72 µm (IQR 38.5). The mean pRNFL at baseline was significantly lower than the mean normative values. Only subjects with PD showed pRNFL change close to statistical significance. This study confirms the role of SD-OCT in managing OPGs for therapeutic decisions and strategy planning of visual rehabilitation.

Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.

A low-cost and disposable graphene polylactic (G-PLA) 3D-printed electrode modified with gold particles (AuPs) was explored to detect the cDNA of SARS-CoV-2 and creatinine, a potential biomarker for COVID-19. For that, a simple, non-enzymatic electrochemical sensor, based on a Au-modified G-PLA platform was applied. The AuPs deposited on the electrode were involved in a complexation reaction with creatinine, resulting in a decrease in the analytical response, and thus providing a fast and simple electroanalytical device. Physicochemical characterizations were performed by SEM, EIS, FTIR, and cyclic voltammetry. Square wave voltammetry was employed for the creatinine detection, and the sensor presented a linear response with a detection limit of 0.016 mmol L−1. Finally, a biosensor for the detection of SARS-CoV-2 was developed based on the immobilization of a capture sequence of the viral cDNA upon the Au-modified 3D-printed electrode. The concentration, immobilization time, and hybridization time were evaluated in presence of the DNA target, resulting in a biosensor with rapid and low-cost analysis, capable of sensing the cDNA of the virus with a good limit of detection (0.30 µmol L−1), and high sensitivity (0.583 µA µmol−1 L). Reproducible results were obtained (RSD = 1.14%, n = 3), attesting to the potentiality of 3D-printed platforms for the production of biosensors.

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment.

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43–16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.

During the complementary feeding period, any nutritional deficiencies may negatively impact infant growth and neurodevelopment. A healthy diet containing all essential nutrients is strongly recommended by the WHO during infancy. Because vegetarian diets are becoming increasingly popular in many industrialized countries, some parents ask the pediatrician for a vegetarian diet, partially or entirely free of animal-source foods, for their children from an early age. This systematic review aims to evaluate the evidence on how vegetarian complementary feeding impacts infant growth, neurodevelopment, risk of wasted and/or stunted growth, overweight and obesity. The SR was registered with PROSPERO 2021 (CRD 42021273592). A comprehensive search strategy was adopted to search and find all relevant studies. For ethical reasons, there are no interventional studies assessing the impact of non-supplemented vegetarian/vegan diets on the physical and neurocognitive development of children, but there are numerous studies that have analyzed the effects of dietary deficiencies on individual nutrients. Based on current evidence, vegetarian and vegan diets during the complementary feeding period have not been shown to be safe, and the current best evidence suggests that the risk of critical micronutrient deficiencies or insufficiencies and growth retardation is high: they may result in significantly different outcomes in neuropsychological development and growth when compared with a healthy omnivorous diet such as the Mediterranean Diet. There are also no data documenting the protective effect of vegetarian or vegan diets against communicable diseases in children aged 6 months to 2–3 years.

Probiotic bacteria are microorganisms with beneficial effects on human health and are currently used in numerous food supplements. However, no selection process is able to effectively distinguish probiotics from non-probiotic organisms on the basis of their genomic characteristics. In the current study, four Machine Learning algorithms were employed to accurately identify probiotic bacteria based on their DNA characteristics. Although the prediction accuracies of all algorithms were excellent, the Neural Network returned the highest scores in all the evaluation metrics, managing to discriminate probiotics from non-probiotics with an accuracy greater than 90%. Interestingly, our analysis also highlighted the information content of the tRNA sequences as the most important feature in distinguishing the two groups of organisms probably because tRNAs have regulatory functions and might have allowed probiotics to evolve faster in the human gut environment. Through the methodology presented here, it was also possible to identify seven promising new probiotics that have a higher information content in their tRNA sequences compared to non-probiotics. In conclusion, we prove for the first time that Machine Learning methods can discriminate human probiotic from non-probiotic organisms underlining information within tRNA sequences as the most important genomic feature in distinguishing them.

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor β cell–cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

Several institutions propose responsive feeding (RF) as the caregivers’ relational standard when nurturing a child, from breast/formula feeding onwards. Previous systematic reviews (SRs) on caregivers’ feeding practices (CFPs) have included studies on populations from countries with different cultures, rates of malnutrition, and incomes, whereas this SR compares different CFPs only in healthy children (4–24 months) from industrialized countries. Clinical questions were about the influence of different CFPs on several important outcomes, namely growth, overweight/obesity, risk of choking, dental caries, type 2 diabetes (DM2), and hypertension. The literature review does not support any Baby Led Weaning’s or Baby-Led Introduction to SolidS’ (BLISS) positive influence on children’s weight–length gain, nor their preventive effect on future overweight/obesity. RF-CFPs can result in adequate weight gain and a lower incidence of overweight/obesity during the first two years of life, whereas restrictive styles and coercive styles, two kinds of non-RF in CF, can have a negative effect, favoring excess weight and lower weight, respectively. Choking risk: failure to supervise a child’s meals by an adult represents the most important risk factor; no cause–effect relation between BLW/BLISS/RF/NRCF and choking could be found. Risks of DM2, hypertension, and caries: different CFPs cannot be considered as a risky or preventive factor for developing these conditions later in life.

Background: A convincing association between the foot and ankle alignment (FAA) and patellofemoral pain syndrome (PFPS) remains debatable in the literature. Therefore, all studies investigating the role of FAA in patients with PFPS were systematically reviewed. Methods: A systematic literature search was performed on the databases PubMed, Embase, Cochrane Library, and Web of Science. Inclusion criteria were all studies investigating static and/or dynamic FAA factors and PFPS. Studies with less than 20 patients or with patellofemoral osteoarthritis were excluded. The quality assessment was based on Cochrane study criteria, and the maximum score was set at eight. Results: Of 2246 articles, only 13 case-control studies were eligible. Considering static FAA factors, two studies found an association with rearfoot eversion and one with rearfoot inversion. While examining dynamic FAA characteristics, one study found an association with rearfoot eversion range of motion and three with gait kinematics. No further associations were reported. The quality assessment mean score was 5.5 (SD = 0.97) corresponding to moderate quality. Conclusions: In contrast to our expectations, a limited number of studies were founded supporting an association between FAA and PFPS. At present, the quality of the literature is still poor and conflicting, thus the need for further studies to determine any association between FAA and PFPS.

Wearable technologies are often indicated as tools that can enable the in-field collection of quantitative biomechanical data, unobtrusively, for extended periods of time, and with few spatial limitations. Despite many claims about their potential for impact in the area of injury prevention and management, there seems to be little attention to grounding this potential in biomechanical research linking quantities from wearables to musculoskeletal injuries, and to assessing the readiness of these biomechanical approaches for being implemented in real practice. We performed a systematic scoping review to characterise and critically analyse the state of the art of research using wearable technologies to study musculoskeletal injuries in sport from a biomechanical perspective. A total of 4952 articles were retrieved from the Web of Science, Scopus, and PubMed databases; 165 were included. Multiple study features—such as research design, scope, experimental settings, and applied context—were summarised and assessed. We also proposed an injury-research readiness classification tool to gauge the maturity of biomechanical approaches using wearables. Five main conclusions emerged from this review, which we used as a springboard to propose guidelines and good practices for future research and dissemination in the field.

Background: Cervical dysplasia persistence/recurrence has a great impact on women’s health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18–89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5–52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

Periodontal disease is a widespread disorder comprising gingivitis, a mild early gum inflammation, and periodontitis, a more severe multifactorial inflammatory disease that, if left untreated, can lead to the gradual destruction of the tooth-supporting apparatus. To date, effective etiopathogenetic models fully explaining the clinical features of periodontal disease are not available. Obviously, a better understanding of periodontal disease could facilitate its diagnosis and improve its treatment. The purpose of this study was to employ a proteomic approach to analyze the gingival crevicular fluid (GCF) of patients with severe periodontitis, in search of potential biomarkers. GCF samples, collected from both periodontally healthy sites (H-GCF) and the periodontal pocket (D-GCF), were subjected to a comparison analysis using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A total of 26 significantly different proteins, 14 up-regulated and 12 down-regulated in D-GCF vs. H-GCF, were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main expressed proteins were inflammatory molecules, immune responders, and host enzymes. Most of these proteins were functionally connected using the STRING analysis database. Once validated in a large scale-study, these proteins could represent a cluster of promising biomarkers capable of making a valuable contribution for a better assessment of periodontitis.