Inflammation and physical activity in multiple sclerosis patients. A systematic review and meta-analysis.

OBJECTIVES: Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients. METHODS: Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION". RESULTS: three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation. CONCLUSIONS: Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.

Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): Pilot study with 18F-Fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-FES PET/CT is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the ET-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in ER+/HER2- metastatic breast cancer (MBC). METHODS: Eligible patients underwent a 18F-FES PET/CT at baseline. Patients with SUV≥2 received single agent ET until PD; patients with SUV<2 were randomized to single agent ET (Arm A) or chemotherapy (CT) (Arm B). Primary objective was to compare the activity of first line ET versus CT in patients with 18F-FES SUV <2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV≥2 and received ET; 30 pts with SUV<2 were randomized to ET or CT. After a median follow up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median PFS was 12.4 months (95%CI 3.1-59.6) in patients with SUV <2 randomised to Arm A versus 23.0 months (95%CI 7.7-30.0) in Arm B, (HR = 0.71, 95%CI 0.3 - 1.7); median PFS was 18.0 months (95%CI 11.2-23.1) in patients with SUV≥2 treated with ET. Median OS was 28.2 months (95%CI 14.2-NE) in patients with SUV <2 randomized to ET (Arm A) versus 52.8 months (95%CI 16.2-NE) in Arm B (CT). Median OS was not reached in patients with SUV≥2. 60-month OS rate was 41.6% (95%CI 10.4-71.1%) in Arm A, 42.0% (95%CI 14.0-68.2%) in Arm B and 59.6% (95%CI 48.6-69.0%) in patients with SUV≥2. In patients with SUV≥2, 60-months OS rate was 72.6% if treated with aromatase inhibitors versus 40.6% in case of fulvestrant or tamoxifen (p<0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Diverging conformations guide dipeptide self-assembly into crystals or hydrogels.

The prediction of dipeptide assembly into crystals or gels is challenging. This work reveals the diverging conformational landscape that guides self-organization towards different outcomes. In silico and experimental data enabled deciphering of the electronic circular dichroism (ECD) spectra of self-assembling dipeptides to reveal folded or extended conformers as key players.

Spatial, temporal and network analyses provide insights into the dynamics of the bacterial communities associated with two species of Caribbean octocorals and indicate possible key taxa.

Despite the current decline of scleractinian coral populations, octocorals are thriving on reefs in the Caribbean Sea and western North Atlantic Ocean. These cnidarians are holobiont entities, interacting with a diverse array of microorganisms. Few studies have investigated the spatial and temporal stability of the bacterial communities associated with octocoral species and information regarding the co-occurrence and potential interactions between specific members of these bacterial communities remain sparse. To address this knowledge gap, this study investigated the stability of the bacterial assemblages associated with two common Caribbean octocoral species, Eunicea flexuosa and Antillogorgia americana, across time and geographical locations and performed network analyses to investigate potential bacterial interactions. Results demonstrated that general inferences regarding the spatial and temporal stability of octocoral-associated bacterial communities should not be made, as host-specific characteristics may influence these factors. In addition, network analyses revealed differences in the complexity of the interactions between bacteria among the octocoral species analyzed, while highlighting the presence of genera known to produce bioactive secondary metabolites in both octocorals that may play fundamental roles in structuring the octocoral-associated bacteriome. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-023-00923-x.

Electronic circular dichroism from real-time propagation in state space.

In this paper, we propose to compute the electronic circular dichroism (ECD) spectra of chiral molecules using a real-time propagation of the time-dependent Schrödinger equation (TDSE) in the space of electronic field-free eigenstates, by coupling TDSE with a given treatment of the electronic structure of the target. The time-dependent induced magnetic moment is used to compute the ECD spectrum from an explicit electric perturbation. The full matrix representing the transition magnetic moment in the space of electronic states is generated from that among pairs of molecular orbitals. In the present work, we show the ECD spectra of methyloxirane, of several conformers of L-alanine, and of the Λ-Co(acac)3 complex, computed from a singly excited ansatz of time-dependent density functional theory eigenstates. The time-domain ECD spectra properly reproduce the frequency-domain ones obtained in the linear-response regime and quantitatively agree with the available experimental data. Moreover, the time-domain approach to ECD allows us to naturally go beyond the ground-state rotationally averaged ECD spectrum, which is the standard outcome of the linear-response theory, e.g., by computing the ECD spectra from electronic excited states.

The Conformational Dynamics of the Ligands Determines the Electronic Circular Dichroism of the Chiral Au38(SC2H4Ph)24 Cluster.

Effects of the conformational dynamics of 2-PET protective ligands on the electronic circular dichroism (ECD) of the chiral Au38(SC2H4Ph)24 cluster are investigated. We adopt a computational protocol in which ECD spectra are calculated via the first principle polTDDFT approach on a series of conformations extracted from MD simulations by using Essential Dynamics (ED) analysis, and then properly weighted to predict the final spectrum. We find that the experimental spectral features are well reproduced, whereas significant discrepancies arise when the spectrum is calculated using the experimental X-ray structure. This result unambiguously demonstrates the need to account for the conformational effects in the ECD modeling of chiral nanoclusters. The present procedure proved to be able of capturing the essential conformational features of the dynamic Au38(SC2H4Ph)24 system, opening the possibility to model the ECD of soluble chiral nanoclusters in a realistic way.

Antibody persistency and trend post-SARS-CoV-2 infection at eight months.

Introduction: A large amount of recent research has focused on the nature of immunity elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly its robustness and the duration of protection it offers. As a vaccine's efficacy relies on its ability to induce a protective immune response, these questions remain particularly pertinent. An improved understanding of the immunity offered by the antibodies developed against SARS-CoV-2 in recovered patients is critical for the development of diagnostic tests and vaccines. Methods: Our study aimed at the longitudinal analysis of antibody presence, persistence and its trend over eight months in a group of 30 COVID-19 recovered patients who tested positive by real-time quantitative PCR for SARS-CoV-2 in the period 1-30 March 2020. The subjects were divided into two groups based on disease severity: mild (n=17 subjects) and moderately-severe (n=13 subjects). The MAGLUMI 2019-nCoV lgM/lgG chemiluminescent analytical system (CLIA) assay was used to analyze these antibody titres. Results: IgG antibody persistency was demonstrated in 76.7 % of the subjects (23 out of 30) at eight months post-infection. For the moderately-severe group, the titre trends for both IgM and IgG changed in a statistically significant way throughout the time period with IgM below and IgG above the set cut-off. Conclusions: The results of this study highlight an important point in terms of the association between humoral immune response and disease severity. Patients who have experienced a relatively severe infection might develop a stronger immune response that could persist for a longer period.

Neutralizing antibody responses against SARS-CoV-2 spike receptor-binding domain 13 months after the recovery from the disease.

BACKGROUND: Information regarding the kinetics and longevity of acquired immunity in recovered COVID-19 patients requires thorough analysis and documentation. This is an update to an ongoing monocentric pilot observational study, that longitudinally analyzed the presence of antibodies after SARS-CoV-2 infection. STUDY DESIGN: Antibody titers against nucleocapsid protein (NCP) of SARS-CoV-2 analyzed at 8 months was followed by adoption of a more specific immunoassay, anti-Spike-Receptor binding domain IgG CLIA for analysis at 12 and 13 months post infection. METHODS: MAGLUMI® SARS-CoV-2 S-RBD IgG Chemiluminescence immunoassay (CLIA) was adopted for measurement of antibody titres at 12 and 13 months after SARS-CoV-2 infection. RESULTS: 97% (34 out of 35) patients resulted positive for anti-SARS-CoV-2 RBD IgG at 12 and 13 months. DISCUSSION AND CONCLUSIONS: In areas with vaccine and resource scarcity, vaccination could be prioritized for those individuals who have never been infected or for the ones who have recovered but show the absence of protective antibodies.

Revealing the electronic properties of the B-B bond: the bis-catecholato diboron molecule.

The electronic properties of a diboron molecule, namely bis(catecholato)diboron (2-(1,3,2-benzodioxaborol-2-yl)-1,3,2-benzodioxaborole) (B2Cat2), have been studied by comparing the results of photoemission (XPS) and near edge X-ray absorption spectroscopy (NEXAFS) experiments with the outcome of DFT calculations. The B 1s, C 1s and O 1s K-edges have been investigated for both the isolated gas phase molecule and the adsorbed one on the Au(111) surface. The main features of the polarized NEXAFS spectra at each of the three edges considered are not significantly affected by the presence of the substrate, with respect to the isolated molecule, indicating that the molecule-gold interaction is weak. Moreover, the comparison between the observed dichroism in the NEXAFS spectra of the adsorbed B2Cat2 and that in the NEXAFS spectra of the isolated molecule has confirmed the orbital symmetry assigned in the gas phase absorption spectra. The transitions to π(B-B) bonding and π*(B-B) anti-bonding final states represent the most relevant probe of the chemistry of the B2Cat2 molecule. We show that their theoretical description requires that the treatment of the relaxation changes among different excited state configurations, which we successfully implemented by using ΔSCF-DFT (ΔSCF) calculations.

Non-adherence to Mediterranean diet and synergy with lifestyle habits in the occurrence of breast cancer: a case-control study in Italy.

OBJECTIVE: The aim of this study was to assess the synergistic effect of non-adherence to the Mediterranean Diet (MD) and lifestyle habits on the occurrence of breast cancer (BC). PATIENTS AND METHODS: A case-control study was carried out from September 2018 to February 2019 at the Teaching Hospital "Umberto I" in Rome. A Food Frequency Questionnaire was used for assessing the level of adherence to MD, the IPAQ Questionnaire to measure physical activity, and AUDIT-C to estimate alcohol consumption. The possible interaction between risk factors was tested using the synergism index. RESULTS: A total of 94 cases and 88 controls were enrolled (median age 55.8 for cases and 57.9 for controls). The MD Score over 6 was associated with low odds of having breast cancer (OR = 0.29; 95% CI: 0.12-0.69). There is a clear indication for the additivity and synergism between non-adherence to MD and many risk factors on the occurrence of BC: current smoker (S = 2.02; 95% CI 0.62-8.07), physical inactivity (S = 2.14; 95% CI 0.71 2-8.28) and alcohol consumption (S = 3.02; 95% CI 0.91-12.95). CONCLUSIONS: Primary prevention of BC can benefit from intervention targeting nutritional and lifestyle factors that act synergistically.

SARS-CoV-2 was already circulating in Italy, in early December 2019.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified in China, in December 2019 determines COronaVIrus Disease 19 (COVID-19). Whether or not the virus was present in Italy earlier the first autochthonous COVID-19 case was diagnosed is still uncertain. We aimed to identify anti-SARS-CoV-2 antibodies in sera collected from 4th November 2019 to 9th March 2020, in order to assess the possible spread of the virus in Italy earlier than the first official national diagnosis. PATIENTS AND METHODS: Anti-SARS-CoV-2 antibodies were evaluated in retrospective serum samples from 234 patients with liver diseases (Hep-patients) and from 56 blood donors (BDs). We used two rapid serologic tests which were confirmed by a validated chemoluminescence assay. RESULTS: Via rapid tests, we found 10/234 (4.3%) IgG-positive and 1/234 (0.4%) IgM-positive cases in the Hep-patient group. Two/56 (3.6%) IgG-positive and 2/56 (3.6%) IgM-positive cases were detected in BD group. Chemoluminescence confirmed IgG-positivity in 3 Hep-patients and 1 BD and IgM-positivity in 1 Hep-patient. RNAemia was not detected in any of the subjects, rendering the risk of transfusion transmission negligible. CONCLUSIONS: Our results suggest an early circulation of SARS-CoV-2 in Italy, before the first COVID-19 cases were described in China. Rapid tests have multiple benefits; however, a confirmation assay is required to avoid false positive results.

Epidemiology of emergency calls for time-dependent acute illnesses during COVID-19 outbreak in Umbria region (Italy).

The recent literature reported an inverse correlation between COVID-19 pandemic and hospital admissions for Acute Coronary Syndromes (ACS).

Development and national consensus finding on patient-centred high stakes communication skills assessments for the Swiss Federal Licensing Examination in Medicine.

OBJECTIVE: To describe and evaluate a consensus finding and expert validation process for the development of patient-centred communication assessments for a national Licensing Exam in Medicine. METHODS: A multi-professional team of clinicians and experts in communication, assessment and role-play developed communication assessments for the Swiss Federal Licensing Examination. The six-month process, informed by a preceding national needs-assessment, an expert symposium and a critical literature review covered the application of patient-centred communication frameworks, the development of assessment guides, concrete assessments and pilot-tests. The participants evaluated the process. RESULTS: The multiple-step consensus process, based on expert validation of the medical and communication content, led to six high-stakes patient-centred communication OSCE-assessments. The process evaluation revealed areas of challenge such as calibrating rating-scales and case difficulty to the graduates' competencies and integrating differing opinions. Main success factors were attributed to the outcome-oriented process and the multi-professional exchange of expertise. A model for developing high stakes patient-centred communication OSCE-assessments was derived. CONCLUSIONS: Consensus finding was facilitated by using well-established communication frameworks, by ensuring outcome-orientated knowledge exchange among multi-professional experts, and collaborative validation of content through experts. PRACTICE IMPLICATIONS: We propose developing high-stakes communication assessments in a multi-professional expert consensus and provide a conceptual model.

Breast surgeons updating on the thresholds of COVID-19 era: results of a multicenter collaborative study evaluating the role of online videos and multimedia sources on breast surgeons education and training.

OBJECTIVE: Current trends show a rise of attention given to breast cancer patients' quality of life and the surgical reconstructive result. Along with this trend, surgical training quality and efficacy are gaining importance and innovative training methods such as online videos shared on social media portals, are becoming main updating tools. In hazardous times like COVID-19 pandemic nowadays, online communication becomes of vital importance and adaptation and innovation are fundamental to keep research and education alive. The authors aimed to investigate the role of video and multimedia sources on the daily activity and surgical training of a representative group of surgeons specifically dedicated to oncologic, oncoplastic and reconstructive breast surgeries. MATERIALS AND METHODS: A survey was produced and administered to 20 major Italian Breast Centers. Collected data were analyzed with Fisher's Exact Test. RESULTS: From October 2019 to March 2020, a total of 320 surveys were collected. Among the responders, there were 188 trainees (intern medical doctors and residents) and 110 faculty, 72% of them belonged to a plastic surgery environment, while 28% to general surgery environment. Almost all respondents have ever watched videos concerning breast surgery. CONCLUSIONS: The results of the study show how breast surgeons rely on videos and web platforms, mostly YouTube, when searching for training info about surgical procedures. Social media offer great opportunities for sharing knowledge and diffusion of new ideas but greater attention to their reliability is mandatory.

Daily music listening to reduce work-related stress: a randomized controlled pilot trial.

BACKGROUND: Literature shows that music can reduce stress conditions. This pilot study investigated the effects of music listening on work-related stress and well-being in healthcare professionals. METHOD: A total of 45 subjects were randomly assigned to three treatment groups: No Music, Individualized Music and Melomics-Health Listening. Music groups experienced a daily 30-min-playlist listening for 3 weeks at home. The Maugeri Stress Index-Revised (MASI-R) and the Psychological General Well-Being Index (PGWBI) were administered at baseline, after 3 weeks and after 7 weeks (follow-up). Longitudinal data were analyzed by means of a nested ANOVA model, testing the main effects of time and treatment and the interaction between them. RESULTS: MASI-R scores showed a positive trend in music groups and a worsening in the control group. Only the interaction time/treatment emerged as supporting a trend toward statistical significance (P = 0.07). PGWBI showed a stability in music groups and a clear decline in controls, without significant effects. CONCLUSIONS: Results from the study support the need for a larger clinical trial: it is suggested that daily music listening could be implemented to reduce work-related stress and that the effects may be related, not only to individual musical preferences and familiarity, but also to specific music structures and parameters.

The biomechanics of the umbilical cord Wharton Jelly: Roles in hemodynamic proficiency and resistance to compression.

The umbilical cord is a complex structure containing three vessels, one straight vein and two coiled arteries, encased by the Wharton Jelly (WJ) a spongy structure made of collagen and hydrated macromolecules. Fetal blood reaches the placenta through the arteries and flows back to the fetus through the vein. The role of the WJ in maintaining cord circulation proficiency and the ultimate reason for arterial coiling still lack of reasonable mechanistic interpretations. We performed biaxial tension tests and evidenced significant differences in the mechanical properties of the core and peripheral WJ. The core region, located between the arteries and the vein, resulted rather stiffer close to the fetus. Finite element modelling and optimization based inverse method were used to create 2D and 3D models of the cord and to simulate stress distribution in different hemodynamic conditions, compressive loads and arterial coiling. We recorded a facilitated stress transmission from the arteries to the vein through the soft core of periplacental WJ. This condition generates a pressure gradient that boosts the venous backflow circulation towards the fetus. Peripheral WJ allows arteries to act as pressure buffering chambers during the cardiac diastole and helps to dissipate compressive forces away from vessels. Altered WJ biomechanics may represent the structural basis of cord vulnerability in many high-risk clinical conditions.

Spontaneous perception of numerosity in pre-school children.

There is strong evidence that humans can make rough estimates of the numerosity of a set of items, almost from birth. However, as numerosity covaries with many non-numerical variables, the idea of a direct number sense has been challenged. Here we applied two different psychophysical paradigms to demonstrate the spontaneous perception of numerosity in a cohort of young pre-school children. The results of both tasks showed that even at that early developmental stage, humans spontaneously base the perceptual choice on numerosity, rather than on area or density. Precision in one of these tasks predicted mathematical abilities. The results reinforce strongly the idea of a primary number sense and provide further evidence linking mathematical skills to the sensory precision of the spontaneous number sense, rather than to mechanisms involved in handling explicit numerosity judgements or extensive exposure to mathematical teaching.

Cardiotoxicity and pro-inflammatory effects of the immune checkpoint inhibitor Pembrolizumab associated to Trastuzumab.

BACKGROUND: The immunotherapy has revolutionized the world of oncology in the last decades with considerable advantages in terms of overall survival in cancer patients. The association of Pembrolizumab and Trastuzumab was recently proposed in clinical trials for the treatment of Trastuzumab-resistant advanced HER2-positive breast cancer. Although immunotherapies are frequently associated with a wide spectrum of immune-related adverse events, the cardiac toxicity has not been properly studied. PURPOSE: We studied, for the first time, the putative cardiotoxic and pro-inflammatory effects of Pembrolizumab associated to Trastuzumab. METHODS: Cell viability, intracellular calcium quantification and pro-inflammatory studies (analyses of the production of Interleukin 1ß, 6 and 8, the expression of NF-kB and Leukotriene B4) were performed in human fetal cardiomyocytes. Preclinical studies were also performed in C57BL6 mice by analyzing fibrosis and inflammation in heart tissues. RESULTS: The combination of Pembrolizumab and Trastuzumab leads to an increase of the intracellular calcium overload (of 3 times compared to untreated cells) and to a reduction of the cardiomyocytes viability (of 65 and 20-25%, compared to untreated and Pembrolizumab or Trastuzumab treated cells, respectively) indicating cardiotoxic effects. Notably, combination therapy increases the inflammation of cardiomyocytes by enhancing the expression of NF-kB and Interleukins. Moreover, in preclinical models, the association of Pembrolizumab and Trastuzumab increases the Interleukins expression of 40-50% compared to the single treatments; the expression of NF-kB and Leukotriene B4 was also increased. CONCLUSION: Pembrolizumab associated to Trastuzumab leads to strong cardiac pro-inflammatory effects mediated by overexpression of NF-kB and Leukotriene B4 related pathways.

NPWTid in the treatment of infected diabetic foot.

Negative Pressure Wound Therapy with instillation therapy and dwelling time (NPWTid) represents a good tool to treat severely infected non-healing wounds. This topical treatment consists of negative pressure and retrograde instillation of antiseptic/antibiotic Romasolutions into the wound surface, to promote cleansing and consequently the healing process. We reported our initial experience (five cases) in the treatment of severely infected diabetic foot, that can be considered a life-threatening condition. In our case reports, patients presented with clinical signs and symptoms of severe sepsis. Our treatment based on multidisciplinary approach (surgical, NPWTid, interventional radiology, skin grafts) had satisfying results. NPWT represented an important support to treatment of these diabetic patients.

Meckel diverticulum: one pathology, different clinical presentations. A report of two cases.

Meckel diverticulum is the most prevalent congenital malformation of gastrointestinal tract and usually it remains asymptomaRomatic. Approximately in 25% of cases Meckel diverticulum comes to be symptomatic with various clinical presentations where lower gastrointestinal hemorrhage or intestinal obstruction represent the most frequent clinical outcome. In present paper two cases of complicated Meckel diverticulum in young patients are described; in both cases diagnosis was difficult and initially mistaken with other pathologies. Surgical resection was the treatment of choice.