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Protein tandem mass spectrometry (MS/MS) often generates sequence-informative fragments from backbone bond cleavages near the termini. This lack of fragmentation in the protein interior is particularly apparent in native top-down mass spectrometry (MS). Improved sequence coverage, critical for reliable annotation of posttranslational modifications and sequence variants, may be obtained from internal fragments generated by multiple backbone cleavage events. However, internal fragment assignments can be error prone due to isomeric/isobaric fragments from different parts of a protein sequence. Also, internal fragment generation propensity depends on the chosen MS/MS activation strategy. Here, we examine internal fragment formation in electron capture dissociation (ECD) and electron transfer dissociation (ETD) following native and denaturing MS, as well as LC/MS of several proteins. Experiments were undertaken on multiple instruments, including quadrupole time-of-flight, Orbitrap, and high-field Fourier-transform ion cyclotron resonance (FT-ICR) across four laboratories. ECD was performed at both ultrahigh vacuum and at similar pressure to ETD conditions. Two complementary software packages were used for data analysis. When feasible, ETD-higher energy collision dissociation MS3 was performed to validate/refute potential internal fragment assignments, including differentiating MS3 fragmentation behavior of radical versus even-electron primary fragments. We show that, under typical operating conditions, internal fragments cannot be confidently assigned in ECD or ETD. On the other hand, such fragments, along with some b-type terminal fragments (not typically observed in ECD/ETD spectra) appear at atypical ECD operating conditions, suggesting they originate from a separate ion-electron activation process. Furthermore, atypical fragment ion types, e.g., x ions, are observed at such conditions as well as upon EThcD, presumably due to vibrational activation of radical z-type ions.

Abstract Background Twin pregnancies present unique challenges in maternal healthcare. However, current guidelines primarily address singleton pregnancies, resulting in a knowledge gap regarding their specific metabolic and dietary needs. This study aimed to follow women with twin pregnancies through all three trimesters, assessing basal metabolic rate (BMR), dietary intake, and diet quality. Methods A two-year prospective observational study was conducted at AOU Careggi Hospital, Florence, Italy, involving 35 twin-pregnant women, with 32 completing the study. Participants underwent calorimetric, anthropometric, and dietary assessments during the first (8–13 weeks), second (14–27 weeks), and third trimesters (28–34 weeks). BMR was measured using indirect calorimetry and compared with predictive equations. Dietary intake was evaluated using 7-day food diaries and the Medi-Lite adherence score. Results Indirect calorimetry revealed an increase in BMR by 16%, rising from 1479 ± 196 kcal in the first trimester to 1733 ± 224 kcal in the third trimester. Hronek’s equation, previously validated for singleton pregnancies, was identified as the most accurate predictive tool for estimating BMR. Dietary analysis revealed that mean daily energy intake increased from 1660 ± 244 kcal in the first trimester to 1889 ± 262 kcal in the third trimester, consistently below recommendations, with insufficient macro- and micronutrient consumption. Poor diet quality was characterized by low intake of fruits, vegetables, legumes, and fresh fish, and high consumption of processed meats, cheese, and sugar-sweetened beverages. Adherence to the Mediterranean diet was moderate across all three trimesters. Conclusions This study highlights the increased energy demands and nutritional inadequacies in twin pregnancies, underscoring the need for tailored dietary guidelines and interventions.

Abstract The geriatric vision of palliative care is based on a multidisciplinary, patient‐centered approach, looking for a balance between human dignity and medical treatments with a particular focus on the social and ethical aspects. In order to develop the best care models, there is a rising need for a tighter collaboration of all the involved players (i.e., doctors, nurses, social workers). Indeed, the idea of a fragmented system without considering the patient or his/her family is not at all applicable to older patients with chronic disease. The causes of death, the phase of death changes, and the extend of last period of life could be a long phase characterized by complicated treatment decisions, difficult management of symptoms, multiple psychosocial problems, and complex spiritual distress. Recently, Italian guidelines on Comprehensive Geriatric Assessment (CGA) have been published. However, none of the identified studies on patients in hospice and other palliative care facilities met the criteria for inclusion. These findings underscore the need for further research to determine the potential benefits of a multidimensional approach for patients in hospice and other palliative care settings. Our reflections and suggestions on the CGA use for older persons in palliative care may be a starting point for an open and continuous dialogue with all the operators concerned.

Abstract Background Patients with cancer (PwC) who undergo specific treatments reported greater fatigue and reduced functional capacity as predominant outcomes, compromising their QoL during and following the treatment. Prehabilitation intervention, provided after diagnosis and before treatments, is to optimize the physiological reserve and address modifiable risk factors before surgery or chemotherapy to improve post-treatment results. The primary aim of this study is to obtain a common line of efficacy compared with prehabilitation treatment; the secondary endpoint is to assess the methodological quality of the studies eligible in the review. Methods The systematic review was conducted from September to February 2024, in accordance with PRISMA guidelines. Databases consulted were MEDLINE, Scopus, Web of science and CINAHL, RCTs related to Prehabilitation intervention on PwC were included. The methodological quality of the included studies was assessed through the RoB2 Cochrane tool and the PEDro scale. Meta-analysis was performed to estimate relative treatment effects among evaluated outcomes. Results Forty-two studies were included in the systematic review, 13 were included in the quantitative analysis. The results of the studies reporting reduced postoperative hospital stay, improved endurance, muscle strength, respiratory function, quality of life, and urinary incontinence. Critical analysis of the articles using the PEDro scale revealed 28 RCTs with a good rating, 9 with a fair rating, and 5 with a poor rating; in contrast, the Cochrane RoB2 tool revealed that all articles were at high risk of bias. Meta-analysis showed statistically significant values for 6MWT (38.53, 95%CI 33.03 - 44.04); HADS-depression (-0.71, 95%CI -0.93 -0.49) and HADS-anxiety (-0.49, 95%CI -0.76 -0.23). Conclusions Prehabilitation represents a specific intervention that aims to improve postoperative outcomes in fragile patients undergoing surgery, increasing their preoperative physiological reserve in anticipation of the stress they will face and facilitating the postoperative recovery of functional capacity. Prehabilitation is a good intervention to use, especially in terms of functional capacity and mental health, the latter being very impactful in terms of reduced levels of anxiety and depression. These data make it possible to justify supportive intervention by physical therapists aimed at improving and restoring health-related QoL especially in the short term.

Abstract Background SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time. Methods SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time. Case presentation Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th. Conclusion Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients.

One of the genetic mutations most associated with the onset of amyotrophic lateral sclerosis, both in sporadic and familial cases, is the expansion of the C9orf72 gene. The presence of more than 30 repeats (GGGGCC) correlates with uncertain ALS symptomatology. Here we collected a dermal biopsy from a subject carrying 36 hexanucleotide repeats and reprogrammed it into an induced pluripotent stem cell line. Despite the number of repeat elements, the subject had no symptoms at the age of the biopsy (76 years), thus resulting in a healthy carrier of the mutation.

The development of cerebral cavernous malformations (CCMs) is a well-recognized sequela of irradiation to the brain in pediatric tumors, particularly in medulloblastoma, glioma, and acute lymphoblastic leukaemia. So far, only one case of cerebral cavernoma after chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has been described. We describe a case of a patient with medulloblastoma aged 18 months at the time of oncological diagnosis who was treated with high-dose chemotherapy followed by HSCT and who developed CCM two years later. The patient was not treated for vascular malformation since he remained asymptomatic until now and is regularly followed with neuro-radiological check-ups. This represents the second case of acquired cavernoma developed in a patient who has not received radiation therapy.

BackgroundTelerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS).Materials and methodsSubjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t-test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t-test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications.ResultsA total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003).ConclusionsBoth SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.

Abstract Background Physical fatigue is one of the most disabling symptoms in people with Multiple Sclerosis (PwMS). Several factors might influence the development of fatigue, such as gender, education, body mass index (BMI), Expanded Disability Status Scale (EDSS), disease duration, working status (Ws), physiotherapy (Ph), and disease-modifying therapies (DMTs). Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a patient-reported outcome (PRO) that allows one to define the impact of fatigue in PwMS clearly. This study aimed to assess fatigue impact on PwMS by using FSIQ-RMS. Methods The participants were enrolled from May to July 2021 in MS Centers of Sant’Andrea Hospital and Policlinico Umberto I Hospital in Rome. Fatigue was evaluated using the FSIQ-RMS, validated, and culturally adapted in Italian. Clinical and demographic data were collected at the same time. Results We enrolled 178 PwMS [Female 74.16%; RMS 82.58%, SPMS 17.52%]. FSIQ-RMS scores were significantly correlated with EDSS (p-value

BackgroundMycotic carotid pseudoaneurysms represent a challenge for surgeons. They are rare and associated with high mortality and morbidity.MethodsWe reported a case of a 61-year-old man with a mycotic pseudoaneurysm of carotid bifurcation. The case was managed by a staged procedure, starting with initial endovascular control using a stent graft, followed by open arterial reconstruction using a saphenous vein graft.ResultsThe patient was discharged home with a patent carotid artery and no sign of infection or bleeding. A computed tomography scan performed at 1 month, 6 months, and 1 year later confirmed good patency of the graft without imaging of cerebral ischemia.ConclusionsMycotic pseudoaneurysms of the extracranial carotid artery are rare and should always be treated surgically. This disease, despite its rarity, requires early detection and treatment to avoid fatal outcomes. A hybrid staged approach is suggested, compared to one-staged surgery, to avoid rupture and improve clinical outcomes. This approach involves using a stent graft combined with antibiotic therapy as bridge treatment until definitive surgery can be performed to enable arterial reconstruction with an autologous graft.

Background: In the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson's disease on QoL of affected individuals. The Short Parkinson's Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson's disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale. Methods: Translation and cultural adaptation were performed. Included patients had diagnosis of Parkinson's disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach's Alpha and construct validity using Pearson's correlation between SPES-SCOPA and the gold standard PDQ-39. Results: 101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach's Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements. Conclusion: This research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

INTRODUZIONE Il sonno è un processo fisiologico caratterizzato da una riduzione dello stato di coscienza e ha un impatto importante sulla qualità della vita (QoL). I disturbi del sonno sono comuni nelle persone affette da Long Covid, complessa condizione clinica caratterizzata dalla comparsa di sintomi a distanza di circa 3 mesi dall’infezione acuta da Sars-CoV-2. Lo scopo di questo studio è valutare le proprietà psicometriche della versione italiana della General Sleep Disturbance Scale (GSDS-IT) nelle persone affette da Long Covid. METODI Questo studio retrospettivo di valutazione delle qualità psicometriche della scala di valutazione General Sleep Disturbance Scale (GSDS) è stato condotto dal Team clinico-riabilitativo del Poliambulatorio San Felice della ASL Roma 2 dal 1 giugno al 10 luglio 2023 su un campione di 58 pazienti affetti da Long Covid. I criteri di inclusione erano l'ammissione ad un programma di riabilitazione respiratoria post-COVID-19; età minima 18 anni; capacità di comunicare; firma del consenso informato. La consistenza interna è stata determinata tramite l'alfa di Cronbach; per la validità di costrutto sono state somministrate la scala a 12 elementi ​​Short Form Health Survey (SF-12), le Attività di Daily Living (ADL) e le Attività Strumentali di Daily Living (IADL). RISULTATI I valori Alpha di Cronbach e la correlazione intra-classe (ICC) per tutte le sottoscale erano statisticamente significativi. È stata trovata una correlazione tra il sonno e la salute mentale, nonché per la scala totale e le ADL. CONCLUSIONI La GSDS è uno strumento valido e affidabile per la valutazione dei disturbi del sonno nei pazienti con Long Covid. Il suo utilizzo in questa tipologia di pazienti è suggerito per rilevare la presenza di disturbi del sonno, in modo che sia i medici che i ricercatori possano prendere le decisioni più appropriate per la cura globale dei pazienti e per migliorare la loro QoL.

Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers.

The aim of the present study was to investigate the role of mental representation processes during the planning, reaching, and use phases of actions with tools commonly used toward the body (TB, e.g., toothbrush) or away from the body (AB, e.g., pencil). In the first session, healthy participants were asked to perform TB (i.e., making circular movements with the toothbrush near the mouth) and AB (i.e., making circular movements with the pencil near the desk) actions both with (i.e., actual use) and without the tool in hand (i.e., the pantomime of tool use). In the second session, the same participants performed a series of mental rotation tasks involving body- (i.e., face and hands) and object-related (i.e., abstract lines) stimuli. The temporal and kinematic analysis of the motor actions showed that the time required to start the pantomimes (i.e., the planning phase) was shorter for the AB action than for the TB action. In contrast, the reaching phase lasted longer for the AB action than for the TB action. Furthermore, the TB pantomime was associated with the performance in the mental rotation of body-related stimuli, especially during the planning and reaching phases, whereas the AB pantomime was more related to the performance in the mental rotation of object-related stimuli, especially during the tool use phase. Thus, the results revealed that the direction of a goal-directed motor action influences the dynamics of the different phases of the motor action and can determine the type of mental images involved in the planning and execution of the action.

Abstract Background Popliteal artery aneurysms (PAAs) need urgent treatment in case of acute thrombosis, distal embolization, or rupture. Few data are available in the literature about the treatment results in these scenarios. The aim of the present study was to evaluate an 11-year multicenter experience in the urgent treatment of PAAs. Methods All symptomatic PAAs surgically treated in two vascular centers between 2010 and 2021 were retrospectively analyzed. In the postoperative period periodical clinical and Duplex-Ultrasound evaluation were performed. The evaluated endpoint was the outcome of urgent PAAs treatment according to their clinical presentation. Statistical analysis was performed by Kaplan-Meier log-rank evaluation and multivariable Cox regression tests. Results Sixty-six PAAs needed an urgent repair. Twelve (18%) patients had a PAA rupture and 54 (82%) had an acute limb ischemia (ALI) due to either distal embolization or acute thrombosis. Patients with ALI underwent bypass surgery in 51 (95%) cases, which was associated with preoperative thrombolysis in 18 (31%) cases. A primary major amputation was performed in 3 (5%) cases. The mean follow-up was 52 ± 21 months with an overall 5-year limb salvage of 83 ± 6%. Limb salvage was influenced only by the number of patent tibial arteries (pTA) [5-years limb salvage 0%, 86 ± 10%, 92 ± 8% and 100% in case of 0, 1, 2 or 3 pTA, respectively (P = .001)]. An independent association of number of pTA and limb loss was found [hazard ratio (HR): 0.14 (95% confidence interval (CI) 0.03–0.6), P = .001]. Overall 5-year survival was 71 ± 7%. Ruptured PAAs were associated with lower 5-year survival compared with the ALI group (48 ± 2% vs. 79 ± 7%, P = .001). The number of pTA (33 ± 20%, 65 ± 10%, 84 ± 10% and 80 ± 10% for 0, 1, 2 and 3 pTA, respectively, P = .001) and the thrombolysis (94 ± 6% vs. 62 ± 10%, P = .03) were associated with higher survival in patients with ALI. There was an independent association of number of pTA and long-term survival [HR 0.15 (95% CI 0.03–0.8), P = .03]. Conclusions PAA rupture is the cause of urgent PAA treatment in almost one fifth of cases, and it is associated with lower long-term survival. ALI can benefit from thrombolysis, and long-term limb salvage and survival are associated with the number of pTA.

Background: Mentalization represents the ability to interpret one’s own and others’ behaviours in terms of intentional mental states. Previous studies have suggested that impairments in mentalization are associated with personality pathology. The aim of our study was to examine the relationships between mentalization and DSM-5 Alternative Model of Personality Disorder Criterion A in a sample of community dwelling adults. Furthermore, since mentalization and personality dysfunction are associated with emotion dysregulation, we aimed to explore the interconnections among these three constructs. Methodology: In a sample of 1225 Italian community dwelling adults and in a sub-sample of 97 participants we evaluated mentalizing ability and personality dysfunction. We relied on two methods that map different mentalization aspects: (a) in the whole sample, we used a self-report questionnaire (Reflective Functioning Questionnaire), and (b) in a sub-sample, we administered a performance test (Movie for the Assessment of Social Cognition). Moreover, in the whole sample, we explored the mediating role of emotion dysregulation on the association between mentalization and personality dysfunction. Results: The results suggested that uncertainty about mental states was a significant predictor of self and interpersonal personality impairment. Considering the sub-sample, interpersonal dysfunction was associated with a mentalization deficit characterized by hypermentalization, hypomentalization and lack of mentalistic abilities. In the whole sample we found that mentalization deficits might affect personality dysfunction via their effect on emotion regulation. Conclusion: Our findings showed that failures in mentalizing can leave an individual vulnerable to personality impairment and support Zettl et al. (2020) work showing that all the dimensions of personality impairment are associated with mentalistic abilities. Moreover, in line with both theoretical and empirical literature, the mediation analyses results could promote the comprehension of the interplay among mentalization, emotion dysregulation and interpersonal dysfunction supporting the psychotherapeutic model that considered these constructs as targets of psychotherapy.