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Mass spectrometry of intact proteins and protein complexes has the potential to provide a transformative level of information on biological systems, ranging from sequence and post-translational modification analysis to the structures of whole protein assemblies. This ambitious goal requires the efficient fragmentation of both intact proteins and the macromolecular, multicomponent machines they collaborate to create through noncovalent interactions. Improving technologies in an effort to achieve such fragmentation remains perhaps the greatest challenge facing current efforts to comprehensively analyze cellular protein composition and is essential to realizing the full potential of proteomics. In this work, we describe the use of a trimethyl pyrylium (TMP) fixed-charge covalent labeling strategy aimed at enhancing fragmentation for challenging intact proteins and intact protein complexes. Combining analysis of TMP-modified and unmodified protein complexes results in a greater diversity of regions within the protein that give rise to fragments, and results in an up to 2.5-fold increase in sequence coverage when compared to unmodified protein alone, for protein complexes up to 148 kDa. TMP modification offers a simple and powerful platform to expand the capabilities of existing mass spectrometric instrumentation for the complete characterization of intact protein assemblies.

Carolina Ciacci,1 Mario Gagliardi,1 Monica Siniscalchi,1 Monica Ruotolo,1 Antonella Santonicola,1 Najla Hajji,1 Fabiana Zingone2 1Celiac Center at Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy; 2Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, ItalyCorrespondence: Carolina CiacciCeliac Center at Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Salerno, 84081, ItalyEmail cciacci@unisa.itIntroduction: Celiac disease (CeD) diagnosis has worldwide shared protocols. Conversely, follow-up of patients is still an object of study. Gluten immunogenic peptide detection in the urine (GIP) appears to be a new and efficient method for dietary gluten control of patients. The present study aims to assess the clinical usefulness of the GIP point-of-care urine test in the follow-up of symptomatic and asymptomatic patients with CeD before and during the COVID-19 lockdown in Italy.Methods: Thirty adult CeD patients on a gluten-free diet (GFD) were enrolled before and during the COVID-19 lockdown through follow-up visits or remote consultation. Patients underwent anthropometrical evaluation, dietetic interview, and State-Trait Anxiety Inventory (STAI). Then, two groups were formed: symptomatic and worried about gluten contamination. Each patient received 5 GIP point-of-care tests to perform a maximum of 5 times in the following 5 weeks in case of symptoms or anxiety state due to hypothesized gluten contamination.Results: Sixteen symptomatic patients and 14 patients with concerns related to gluten contamination were included. There were no differences in age, BMI, compliance to GFD and GIP positive tests between the two groups. Worried group showed a borderline higher level of anxiety than symptomatic group (p = 0.06), with a significant minor percentage of patients reporting “no or low anxiety” (14.3% vs 50% p = 0.03). The symptomatic patients showed a higher rate of diarrhea than worried group (25% vs 0%, p = 0.04). Gluten in urine samples was globally found in 8 out of 30 cases (26.6%).Conclusion: The GIP test is a tool that can be used as a point of care test to assess adequate compliance with GFD and reassure symptomatic CeD patients from the feeling of anxiety for gluten contamination, especially during the COVID-19 pandemic.Keywords: GIP, POCT gluten contamination, GFD, anxiety, burden, celiac disease

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is widely expressed in the central and peripheral nervous systems. This receptor is implicated in both brain development and adult neurogenesis thanks to its ability to mediate acetylcholine stimulus (Ach). Copy number variations (CNVs) of CHRNA7 gene have been identified in humans and are genetically linked to cognitive impairments associated with multiple disorders, including schizophrenia, bipolar disorder, epilepsy, Alzheimer’s disease, and others. Currently, α7 receptor analysis has been commonly performed in animal models due to the impossibility of direct investigation of the living human brain. But the use of model systems has shown that there are very large differences between humans and mice when researchers must study the CNVs and, in particular, the CNV of chromosome 15q13.3 where the CHRNA7 gene is present. In fact, human beings present genomic alterations as well as the presence of genes of recent origin that are not present in other model systems as well as they show a very heterogeneous symptomatology that is associated with both their genetic background and the environment where they live. To date, the induced pluripotent stem cells, obtained from patients carrying CNV in CHRNA7 gene, are a good in vitro model for studying the association of the α7 receptor to human diseases. In this review, we will outline the current state of hiPSCs technology applications in neurological diseases caused by CNVs in CHRNA7 gene. Furthermore, we will discuss some weaknesses that emerge from the overall analysis of the published articles.

Abstract Background: Randomized clinical trials (RCT) are the foundation for medical advances, but participant recruitment remains a persistent barrier to their success. This retrospective data analysis aims to (1) identify clinical trial features associated with successful participant recruitment measured by accrual percentage and (2) compare the characteristics of the RCTs by assessing the most and least successful recruitment, which are indicated by varying thresholds of accrual percentage such as ≥ 90% vs ≤ 10%, ≥ 80% vs ≤ 20%, and ≥ 70% vs ≤ 30%. Methods: Data from the internal research registry at Columbia University Irving Medical Center and Aggregated Analysis of ClinicalTrials.gov were collected for 393 randomized interventional treatment studies closed to further enrollment. We compared two regularized linear regression and six tree-based machine learning models for accrual percentage (i.e., reported accrual to date divided by the target accrual) prediction. The outperforming model and Tree SHapley Additive exPlanations were used for feature importance analysis for participant recruitment. The identified features were compared between the two subgroups. Results: CatBoost regressor outperformed the others. Key features positively associated with recruitment success, as measured by accrual percentage, include government funding and compensation. Meanwhile, cancer research and non-conventional recruitment methods (e.g., websites) are negatively associated with recruitment success. Statistically significant subgroup differences (corrected p-value < .05) were found in 15 of the top 30 most important features. Conclusion: This multi-source retrospective study highlighted key features influencing RCT participant recruitment, offering actionable steps for improvement, including flexible recruitment infrastructure and appropriate participant compensation.

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease where xerophthalmia, xerostomia and presence of anti-SSA and anti-SSB antibodies are typical features. Its prevalence is higher in over-65 aged population than in other age groups. In the elderly, pSS diagnosis comes up against a whole series of critical points that may favor its misdiagnosis. The aim of our article is to discuss the most relevant of them: the frequent occurrence of a seronegative subset, the presence of systemic features not related to sicca syndrome, the sicca syndrome as iatrogenic manifestation and the possibility of a biopsy false negative of labial salivary glands.

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease affecting both upper and lower motoneurons. The transactive response DNA binding protein (TARDBP) gene, encoding for TDP-43, is one of the most commonly mutated gene associated with familial cases of ALS (10%). We generated a human induced pluripotent stem cell (hiPSC) line from the fibroblasts of an asymptomatic subject carrying the TARDBP p.G376D mutation. This mutation is very rare and was described in a large Apulian family, in which all ALS affected members are carriers of the mutation. The subject here described is the first identified asymptomatic carrier of the mutation.

Abstract The global number of COVID‐19 infections, as of December 23, 2020, stood at approximately 79 million, with over 1.7 million deaths. The development of vascular inflammation may also contribute to a hypercoagulable state and endothelial dysfunction in such patients. It is known that multi‐organ damage is more likely in patients with sepsis if they develop coagulopathy and that inhibition of thrombin synthesis can have a positive impact in reducing mortality. In this review, we will focus on the protection of the most fragile groups of the population, such as the elderly. This segment of the population will be a key issue and probably of primary interest to all. Biomarkers appear to be extremely useful as an indicator of what is happening from a pathophysiological point of view in the heart, allowing us to better stratify the prognosis of our patients affected by COVID‐19, especially in the most severe cases and those with comorbidities.

Longer life expectancy and global population growth result in new environmental demands to meet different material and psychological needs across the lifespan. Since the physical environment is a fundamental factor in the quality of life, here we investigated which different indoor features (i.e., colors, materials/textures) have the most positive impact on individuals in terms of emotional reactions and whether these reactions could vary with age. Four groups of participants (i.e., younger adults, adults, middle-aged, elderly, age range 19–86 years) were presented with pictures of five different rooms: (1) Modern (white and cold colors with good-quality essential coverings); (2) Basic (white and blue colors; plastic and metal furniture); (3) Vivacious (red, blue, and green elements; soft-textured materials); (4) Comfort (different shades of blue and green; velvet coverings); (5) Nature (brown, orange, and green colors; wood furniture and leather coverings). Participants underwent a six-item questionnaire evaluating their positive and negative reactions to each image. The results showed a more positive evaluation of nature and vivacious rooms than all others. In turn, basic and modern rooms evoked more negative emotions than all others. Aged-related emotional reactions emerged, with the elderly appearing to be more inclined to rely on features, such as colors and covering materials, for the affective evaluation of the environment compared to adults and middle-aged adults. These preliminary results support the need for human-centered design approaches to improve well-being across the lifespan.

Background/Objective: Parkinson's disease (PD), a prevalent neurodegenerative disorder, leads to motor and non-motor impairments, affecting quality of life. Camptocormia can be one of the motor signs of PD, characterized by a severe and abnormal forward flexion of the thoracolumbar spine that typically occurs when walking or standing. The following study aims to verify whether postural gymnastics can be an effective treatment for trunk control, balance, activities of daily living, and general well-being in patients with early-stage PD and camptocormia. Methods: Nine participants (mean age 67.7 ± 7.8) with early PD (Hoehn and Yahr Scale ≤ 2) received 10 biweekly physiotherapy sessions. Outcomes were measured using the Parkinson's Disease Questionnaire (PDQ-39) and Berg Balance Scale (BBS) along with trunk mobility and muscle tests according to the Medical Research Council (MRC) scale. Results: Statistically significant results were noted in the PDQ-39 mobility, ADLs and emotional well-being subscales and in the BBS; statistically significant improvements were also seen in trunk mobility and muscle strength. Conclusions: This study shows that the postural gymnastic treatment, according to Souchard, in patients with PD's camptocormia has obtained good results and has the potential timprove mobility and balance, encouraging and motivating patients in their rehabilitation journeys. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Posterolateral corner and arcuate fractures can cause significant disruption to the stability and kinematics of the knee. This study aimed to determine the biomechanical performance of a novel spiked washer (SW) and intramedullary screw technique compared with a tension slide technique (TST) for the repair of arcuate fractures. Sixteen matched fresh-frozen cadaver knees underwent repair. Each specimen underwent transection of the posterolateral corner and lateral capsule along with a proximal fibula osteotomy to simulate an arcuate fracture. Eight specimens underwent repair with a SW technique and 8 underwent repair with a TST. Each specimen underwent cyclic loading followed by load to failure. Gap formation, ultimate load to failure, energy to failure, and stiffness were assessed. The SW technique had significantly less gap formation and higher load to failure. Furthermore, the SW technique had significantly higher stiffness and energy to failure. A SW and screw technique provided a significantly stronger construct with less gap formation when compared with a TST. [Orthopedics. 2024;47(5):e277–e281.] [ABSTRACT FROM AUTHOR]

Background: Telerehabilitation (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 methods: Subjects 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. Results: A 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). Conclusions: Both 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 FROM AUTHOR]

Abstract Hydroxychloroquine (HCQ) is an antimalarial drug also known to have anti‐inflammatory and antiviral effects. The antiviral action of HCQ has been a point of interest for many researchers because of its mechanism of action and the potential use it could have during the current COVID‐19 pandemic. However, HCQ can cause QT interval prolongation. The current therapies used in COVID‐19 are changing as the pandemic develops. The aim of this article is to promote a validated risk score for QT prolongation in multidimensional assessment of COVID‐19 patients, especially in elderly and polypathological patients.

Spy is an ATP independent chaperone that can act as both a holdase and a foldase towards topologically simple substrates. Assessing the interaction of Spy and apoflavodoxin, a complex client, the authors show that Spy’s activity is substrate specific. Spy binds partially unfolded states of apoflavodoxin tightly, which limits the possibility of folding and converts Spy to a pure holdase.