American University of Rome

Language characteristics reflect the ability to connect emotions to words and thoughts, thus transforming non-verbal material into material that can be communicated to others, allowing people to share their emotional experience with others and to regulate their own emotions. In this review, we present the results from the last decade by the three main university research groups (Universities of Rome, Bergamo, and Padua) on Italian computerized linguistic measures of the Referential Process (RP). We discuss 22 studies across several clinical and non-clinical settings and populations, exploring the application of RP measures to heterogeneous materials, such as transcripts of validated clinical instruments, expressive writings, autobiographical memories, dreams, and the therapists’ clinical notes. We also consider the associations between linguistic measures and psychological constructs. The results show the existence of definite linguistic characteristics in the different samples examined. Specifically, a higher use of sensory-somatic words appears to be associated with depressive states, while a greater use of abstract words is associated with defensive dimensions. Additionally, RP measures seem to capture the affective dysregulation features shown by individuals with higher alexithymia scores, indicating reduced symbolizing and affective capabilities. In general, these findings confirm a strong association between language and bodily functioning, highlighting the connection between physical arousal, emotion, thoughts, and health/pathology dimensions.

Background Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the expansion of a CGG repeat in the 5’UTR of the FMR1 (fragile X messenger ribonucleoprotein 1) gene. Healthy individuals possess a repeat 30–55 CGG units in length. Once the CGG repeat exceeds 200 copies it triggers methylation at the locus. This methylation covers the FMR1 promoter region and silences expression of the gene and the production of FMRP (fragile X messenger ribonucleoprotein). The loss of FMRP is responsible for a number of pathologies including neurodevelopmental delay and autism spectrum disorder. Methylation of the expanded repeat in the FMR1 locus is the causal factor for FXS, however it is not known why the expanded repeat triggers this epigenetic change or how exactly DNA methylation is established. Intriguingly, genetic engineering of expanded CGG repeats of over 300 copies in the FMR1 locus in mice remains unmethylated. Also in humans, in very rare cases, individuals can have an FMR1 CGG expansion > 200 copies but the locus remains unmethylated. These unmethylated full mutation (UFM) individuals give us a rare opportunity to investigate the mechanism of FMR1 promoter methylation. Methods Fibroblasts were obtained from a healthy control, an FXS patient and two unmethylated full expansion carriers. RNA was extracted and comparative transcriptomic analysis was performed on all samples. Whole genome sequencing was carried out on DNA from the two UFM carriers and the results analysed to investigate DNA variants that could explain the observed differences in gene expression. Results Our analyses focused on genes involved in epigenetic modification. We show that Tet methylcytosine dioxygenase 3 (TET3), a gene involved in DNA methylation, is significantly downregulated in UFM carriers compared to healthy controls or FXS patient derived cells. Genomic analyses reveal a number of rare variants present in the TET3 locus in UFM carriers when compared to the reference genome. However, no clear modifying TET3 variants were identified. Conclusion Our results suggest that TET3 is a candidate factor responsible for the lack of methylation of the expanded FMR1 locus. Further analyses are needed to further elucidate this relationship, however given its potential to directly interact with CGG repeats and its ambiguous role in 5-hydroxy-methylation of CG containing sequences, TET3 is a strong candidate for further exploration.

The absence of agreed methods to diagnose Achilles tendinopathy impedes research and clinical practice. This gap results in heterogeneous and/or poorly described study samples, making it challenging to apply findings in clinical practice. The aim of this Delphi study was to define consensus on (1) diagnostic domains; (2) differential diagnoses; and (3) conditions requiring further medical attention, when assessing for Achilles tendinopathy. We conducted a sequential three-stage process which included: (1) identifying diagnostic domains, differential diagnoses and conditions requiring further medical attention based on existing scoping reviews and clinical practice guidelines; (2) developing Delphi survey questions; and (3) administering a five-round Delphi online survey. Consensus was defined as ≥70% agreement. 52 participants completed the surveys. Four diagnostic domains were deemed essential and reached consensus (pain location (93%); pain during activity (97%); tests that provoke pain (87%); palpation to assess pain (83%)). 15 differential diagnoses reached consensus: 2 for both midportion and insertional (partial tear (80%); posterior ankle impingement (78%)), 6 for midportion (plantaris tendinopathy (84%); tibialis posterior or flexor hallucis longus tendinopathy/tenosynovitis (72%); flexor digitorum longus tendinopathy (77%); accessory soleus muscle (74%); paratendinopathy (86%); sural nerve neuropathy (81%)) and 7 for insertional (superficial (88%) and retrocalcaneal bursitis (86%); Haglund’s/calcaneal exostosis (80%), intratendinous calcifications (73%); Sever’s disease (78%); calcaneal stress reaction/fracture (80%); subtalar/ankle pain (71%)). Six conditions requiring further medical attention reached consensus: (Achilles tendon rupture (83%); systemic inflammatory joint disease (86%); metabolic syndrome (75%); familial hypercholesterolaemia (77%); endocrine and hormonal disorders (80%); drug reactions (77%)). This consensus identified essential diagnostic domains, differential diagnoses and conditions requiring further medical attention that should be considered when assessing for Achilles tendinopathy.

Autopsy is generally regarded as the gold standard for cause of death determination, the most accurate contributor to mortality data. Despite this, autopsy rates have substantially declined, and death certificates are more frequently completed by clinicians. Substantial discrepancies between clinician-presumed and autopsy-determined cause of death impact quality control in hospitals, accuracy of mortality data, and, subsequently, the applicability and effectiveness of public health efforts. This problem is compounded by wavering support for the practice of autopsy by accrediting bodies and academic bodies governing pathology specialty training. In forensic settings, critical workforce shortages combined with increased workloads further threaten sustainability of the practice. Postmortem imaging (PMI) can help mitigate these ongoing problems. Postmortem computed tomography can help clarify manner and cause of death in a variety of situations and has undeniable advantages, including cost reduction, the potential to review data, expedient reporting, archived unaltered enduring evidence (available for expert opinion, further review, demonstrative aids, and education), and (when feasible) adherence to cultural and religious objections to autopsy. Integration of radiology and pathology is driving a transformative shift in medicolegal death investigations, enabling innovative approaches that enhance diagnostic accuracy, expedite results, and improve public health outcomes. This synergy addresses declining autopsy rates, the forensic pathologist shortage, and the need for efficient diagnostic tools. By combining advanced imaging techniques with traditional pathology, this collaboration elevates the quality of examinations and advances public health, vital statistics, and compassionate care, positioning radiology and pathology as pivotal partners in shaping the future of death investigations.

When asked about their health status, people sometimes intentionally respond inaccurately, such as pretending to feel better or worse than they actually do. This behaviour is often referred to as 'faking' and can be motivated by various reasons, including the desire to gain certain benefits or avoid negative consequences. In this study, we explored whether personality traits Machiavellianism, narcissism, psychopathy and sadism (i.e., the Dark Tetrad) are related to three aspects of faking bad and faking good behaviour. Specifically, we looked at the relationship of students' (N = 215) scores on the Short Dark Tetrad scale (SD4) and their (1) spontaneous faking behaviour (i.e., honest responses on Inventory of Problems-29, faking bad measure , and on Supernormality Scale, faking good scale); (2) Self-reported history of faking bad and faking; and (3) Propensity to fake in civil and criminal contexts. Propensity to faking bad and faking good was investigated using vignettes including both civil and criminal contexts (Faking Bad civil n = 54; Faking Bad criminal n = 54; Faking Good civil n = 54; or Faking Good criminal n = 53) after which students were asked to rate their willingness to fake in depicted situations. The results indicated that Machiavellianism, psychopathy and sadism were associated with spontaneous faking bad, whereas narcissism was linked to spontaneous faking good. Additionally, no significant relationship emerged between Dark Tetrad traits and the history of faking behaviour. Lastly, Machiavellianism was positively associated with a greater propensity to fake, regardless of the context.

From a positive psychological standpoint, access to decent work extends beyond fulfilling economic needs: it is a fundamental human right. While significant efforts have been made to examine the societal implications of decent work, surprisingly little attention has been directed toward its impact on individual employees. Integrating the Conservation of Resources theory and the Self-Determination theory, this study aims to advance understanding of this topic by exploring the dynamic and reciprocal interplay among decent work, flourishing (namely, an indicator of strong individual well-being), and job performance. Data were collected from 426 Italian employees (62.7% female) by administering a survey in three waves with a one-month lag. A Cross-Lagged Panel Model approach was employed. The findings highlight that (a) decent work is positively associated with later flourishing; (b) flourishing positively affects later job performance; (c) flourishing fully mediates the relationship between decent work and job performance; and (d) the relationship between flourishing and decent work is reciprocal, with flourishing also enhancing the perception of decent work over time. Our study contributes to advancing the understanding of decent work and its implications, demonstrating the importance of promoting a decent work environment to foster flourishing and performance. This creates a mutually reinforcing cycle of well-being and productivity.

Graphene Oxide (GO) is a two-dimensional (2D) nanomaterial largely exploited in many fields. Its preparation, usually performed from graphite in an oxidant environment, generally affords 2D layers with a broad size distribution, with overoxidation easily occurring. Here, we investigate the formation, along the Hummers synthesis of GO, of carbon nanoparticles (CNPs) isolated from GO and characterized through morphological and spectroscopic techniques. The purification methodology here applied is based on dialysis and results highly advantageous, since it does not involve chemical processes, which may lead to modifications in the composition of GO layers. Using a cross-matched characterization approach among different techniques, such as x-ray photoelectron spectroscopy, cyclic voltammetry and fluorescence spectroscopy, we demonstrate that the isolated CNP are constituted by layers that are highly oxidized at the edges and are stacked due to π–π interaction among their aromatic basal planes and H–bonded via their oxidized groups. These results, while representing a step forward in the comprehension of the structure of long-debated carbon debris in GO, strongly point to the introduction of dialysis as an indispensable step toward the preparation of more controlled and homogeneous GO layers and to its use for the valorization of low molecular weight GO species as luminescent CNPs.

Background We hypothesize that the rate of change in upper (ΔUMN) and lower (ΔLMN) motor neuron signs from symptom onset to first clinical assessment represent best predictors of survival and disease progression in amyotrophic lateral sclerosis (ALS) compared to singular quantification of UMN and LMN involvement. Methods A retrospective inpatient cohort of 1000 ALS patients was evaluated. The burden of UMN and LMN signs was assessed using the Penn Upper Motor Neuron Score and Lower Motor Neuron Score, respectively. For 421 patients, we compute the ENCALS survival model. Univariate and regularized Cox regressions were conducted to estimate the effect of the aforementioned variables on survival. The ROC curve analysis was then employed to a training sub-cohort to identify a ΔLMN cut-off value discriminating ALS patients with prolonged vs short survival. This cut-off value was then cross validated on a test sub-cohort. A multinomial regression model was used to compare different ΔUMN and ΔLMN scores among ENCALS groups. Results ΔUMN and ΔLMN showed a negative association with survival (ΔUMN: HR = 1.30; ΔLMN: HR = 4.22). A cut-off value of 0.22 for ΔLMN was identified to predict patients with estimated short vs prolonged survival. ENCALS groups characterized by shorter survival presented significantly higher ΔUMN and ΔLMN scores compared to those with longer survival. No significant association of PUMNS or LMNS gross scores with the above-mentioned variables was observed. Conclusion By reflecting the progressing degeneration of the two distinct motor neuron subpopulations, ΔUMN and ΔLMN might represent reliable and easily measurable clinical indexes to estimate survival in ALS.

Detecting ionizing radiation, whether from natural source or due to accidental or intentional nuclear explosions, is a critical and complex challenge for modern technology. Geiger-Muller tube is one of the most used technologies for the detection of gamma radiation. Although it was developed in the early of twentieth century, its simplicity, robustness, affordability, and reliability have ensured its continued widespread use. Moreover, simple electronics make it easy to integrate with modern hardware and software technologies. In this work, we will explore the theoretical principles behind radiation detection and, starting from the analysis and development of several open-source prototypes, we will lead to the design and implementation of both hardware and software. Additionally, we will expose the testing of a radiological detector prototype optimized for gamma radiation detection. Feasible applications of the device will be examined, along with potential innovations such as minimization and integration into multi sensor platforms or wearable systems. In the paper, a comparison of several devices has been studied along with the development of a new detector based on Geiger-Muller tubes, by using low-cost, commercially available technologies. A comparison between four open-source devices and the created prototype are presented and discussed.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease influenced by genetic, lifestyle, and environmental factors. While MASLD is more prevalent in men, women are at increased risk after menopause, highlighting the critical pathogenetic role of sex hormones. The complex interplay between estrogen deficiency, visceral fat accumulation, metabolic syndrome (MetS), and inflammation accelerates disease progression, increases cardiovascular (CV) risk, and triggers a cycle of worsening adiposity, metabolic dysfunction, and psychological problems, including eating disorders. Weight loss in postmenopausal women can significantly improve both metabolic and psychological outcomes, helping to prevent MASLD and related conditions. This review examines the prevalence of MASLD, its comorbidities (type 2 diabetes T2D, CV, mental disorders), pathogenetic mechanisms, and pharmacological treatment with GLP-1 receptor agonists (GLP1-RAs), with a focus on postmenopausal women. Given the use of GLP1-RAs in the treatment of obesity and T2D in MASLD patients, and the increase in MetS and MASLD after menopause, this review analyzes the potential of a stable GLP-1–estrogen conjugate as a therapeutic approach in this subgroup. By combining the synergistic effects of both hormones, this dual agonist has been shown to increase food intake and food reward suppression, resulting in greater weight loss and improved insulin sensitivity, glucose, and lipid metabolism. Therefore, we hypothesize that this pharmacotherapy may provide more targeted therapeutic benefits than either hormone alone by protecting the liver, β-cells, and overall metabolic health. As these effects are only supported by preclinical data, this review highlights the critical need for future research to evaluate and confirm the mechanisms and efficacy in clinical settings, particularly in postmenopausal women.

Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel-Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp, and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥ 30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors, and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery, and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these 6 mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n=19) followed by p.Arg161Ter (n=10). All pairwise comparisons of mutations affecting different codons showed at least one significant (p<0.05) difference, except for p.Asn78Ser vs. p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.

BACKGROUND Ventricular-arterial coupling (VAC) is altered by aging and cardiovascular comorbidities, indicating myocardial dysfunction and/or arterial stiffness. Our aim was to demonstrate whether lifestyle changes and anti-hypertensive drug treatment would improve VAC in recently diagnosed, early stage middle-aged hypertensives (HTN) without organ damage. METHODS Arterial elastance (Ea), carotid-femoral pulse wave velocity (cfPWV), global longitudinal strain (GLS), and myocardial work (MW) [global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE)] were investigated. This retrospective observational study involved 126 individuals (mean age 40 years; 55% female), divided into HTN and normotensives, NT. Clinical, echocardiographic and echo vascular parameters were assessed. Lifestyle changes were recommended for HTN. If blood pressure (BP) values still remained high, anti-hypertensive drug treatment was administered. RESULTS Higher values of systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), GWI, GCW, and GWW were observed in HTN. By following lifestyle changes, BP [diastolic blood pressure (DBP) and MAP], HR, VAC, Ea, cfPWV, GWE, and GLS were changed in HTN; after 6 months of anti-hypertensive drug treatment, BP (SBP, DBP and MAP), HR, VAC, Ea, cfPWV, GWI, GCW, GWW, GWE, and GLS were found to be changed. VAC was linearly related to cfPWV and GLS at two follow ups. No statistically significant difference in VAC between HTN and NT was found. CONCLUSIONS Along with a decrease in BP, smoking cessation, and HR control highlighted a significant role in cardiovascular prevention by improvement of VAC, Ea, cfPWV, GLS and MW.

Background Understanding the relationship between serum ferritin levels and cardiovascular outcomes in type 2 diabetes is crucial for improving risk stratification and guiding therapeutic interventions aimed at preventing major adverse cardiovascular events (MACE). This study aimed to identify distinct clusters of individuals with type 2 diabetes who have varying risks of MACE using a data-driven clustering approach. Methods This retrospective cohort study analyzed data from 49,506 individuals within a multicenter, population-based primary care registry in Catalonia, Spain. Individuals diagnosed with type 2 diabetes at age 35 or older were recruited between January 2010 and December 2021 and followed for at least 10 years. Biomarkers associated with cardiovascular risk—including serum glucose, HbA1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, serum ferritin, leukocyte, and monocyte counts—were examined. Clustering analysis was applied to identify patient subgroups, and Cox proportional hazards models were used to assess associations with cerebrovascular events, coronary events, and composite MACE. Results Five distinct clusters were identified, characterized by differences in serum glucose, HbA1c, lipid profiles, blood pressure, and serum ferritin levels. Individuals with discordantly high serum ferritin levels relative to their body mass index (BMI) exhibited a lower risk of adverse cardiovascular outcomes. In men, hazard ratios (HR) were 0.68 (95% confidence interval [CI]: 0.53–0.87) for cerebrovascular events, 0.65 (95% CI 0.49–0.88) for coronary events, and 0.68 (95% CI 0.56–0.83) for MACE. In women, HRs were 0.81 (95% CI 0.67–0.92) for cerebrovascular events, 0.73 (95% CI 0.57–0.95) for coronary events, and 0.79 (95% CI 0.67–0.92) for MACE. Conclusions Individuals with type 2 diabetes who exhibit higher-than-expected serum ferritin levels relative to their BMI may have a lower risk of cardiovascular events. These findings suggest that ferritin may play a more complex role in cardiovascular risk than previously assumed and highlight the potential for refined risk stratification strategies in type 2 diabetes management. Graphical abstract

Despite the availability of several drug classes for the treatment of hypertension, the current approaches to high blood pressure (BP) are not fully satisfying the needs of this patient population. As a result, in recent years, many clinical trials have investigated novel pharmacological approaches for lowering high BP. As overactivity of the renin–angiotensin–aldosterone system is often present in hypertensive patients, especially those with resistant hypertension, several studies have focused on novel strategies to counteract this phenomenon by the use of non-steroidal inhibitors of the mineralocorticoid receptors, aldosterone synthase inhibitors or RNA-targeting therapies to inhibit the hepatic synthesis of angiotensinogen. The latter approach in particular might offer the additional advantage of reducing the daily pill burden of these patients, hence mitigating the common occurrence of non-adherence to treatment. Because obesity and diabetes are common risk factors for hypertension (a high percentage of individuals with resistant hypertension being obese), numerous investigations have analyzed the BP-lowering effects of those agents, such as glucagon-like peptide-1 receptor agonists and sodium–glucose co-transporter-2 inhibitors, which have been shown to reduce body weight and improve cardiovascular outcomes in these patients. Available evidence suggests that these drug classes can indeed afford a clinically meaningful BP decrease and, potentially, reduce the treatment burden. In conclusion, even though the rates of uncontrolled hypertension remain high, several novel therapeutic options are in the offing. As these emerging treatments will compound with many already available agents, future efforts should be directed at better phenotyping patients to tailor the most suitable approach for each one.

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder associated with the FMR1 gene premutation, characterized by the presence of 55 to 200 CGG triplet repeat expansions. Although the initial symptoms of FXTAS typically manifest in males around the age of 60 with motor symptoms and cognitive deficits, the presentation and progression in females differ. Women, in fact, exhibit a higher prevalence of neuropsychiatric symptoms, with an earlier onset compared to the motor symptoms observed in men. The following article reports on ten cases of women with a diagnosis of FMR1 gene premutation, originating from two medical centers. All the women in the study exhibited neuropsychiatric symptoms and subtle neurological signs as common features. Symptoms typically observed in the male population, such as tremors and cerebellar ataxia, were either absent or significantly reduced in the female cohort. Conversely, there was a higher prevalence of neuropsychiatric symptoms among the women. Neurocognitive impairment was only minimally evident, with mild executive dysfunction and memory complaints noted in a subset of cases. For this reason, we propose the terminology preFXTAS or prodromic FXTAS to define a clinical presentation in women characterized by early manifestations of FXTAS that do not entirely fulfill the established diagnostic criteria but exhibit MRI evidence of white matter alterations suggesting the initiation of the disease process. The study underscores the importance of establishing new diagnostic criteria for FXTAS and, at the same time, developing new biomarkers and interview checklists/assessment scales dedicated to females.

Objectives We conducted a scoping review and analyzed the medical literature on PubMed to assess any potential short-term and long-term benefits of pubertal induction in patients with DMD. Content We identified six articles from our research cumulatively reporting clinical data from 58 pediatric patients with DMD, of age between 12 and 17.7 years. All of them were on glucocorticoid therapy with variable duration and the longest follow-up of 11.7 years. In all patients, the induction protocol was successful (leading to appearance of secondary sexual characteristics); no secondary effects were reported by any analyzed studies. Three papers reported an objective improvement of patients’ quality of life, while in four there was a benefit on the bone profile. Summary Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that affects approximately 1 in 5,000 live-born male children. Because of early and chronic exposure to glucocorticoids, used as standards of care, pubertal development may be variable. While some boys experience a normal pubertal growth spurt, others have testosterone levels below the normal range for age and require pubertal induction therapy to achieve an adequate testicular volume, development of secondary sexual characteristics, and peak bone mass. When and how to use pubertal induction therapy in pediatric patients with DMD is still object of controversy. Outlook The reported evidence of testosterone therapy in patients with DMD is still limited to small cohort sizes, which suggest efficacy and psychosocial benefits.

This paper explores emerging therapies in polycythemia vera and essential thrombocythemia, focusing on thrombosis as a driver of disease progression leading to myelofibrosis, blast phase, second cancers, and mortality. While the thrombosis rate in high‐risk patients has declined, it remains persistently high in low‐risk individuals, with most events being arterial. Inflammation driven by JAK2 V617F mutation plays a primary role in pathogenesis, and mounting evidence suggests arterial thrombosis itself can fuel a self‐sustaining cycle of inflammation, thereby accelerating hematologic and systemic complications. Early intervention with cytoreductive and anti‐inflammatory drugs may not only prevent incidental thrombosis but also disrupt this inflammatory circuit.

The food system significantly impacts biodiversity and environmental health through land-use changes and agrochemical use. However, biodiversity is important for the food supply and the underlying ecosystem services (ES) that support food production. Given the complexity of this relationship, we reviewed 1114 articles following a bibliometric analysis of the literature and we identified 5 research streams: strategies to reduce biodiversity pressure, landscape-scale ecosystem management, agricultural practices’ impact on ES, understanding ES relationships, and soil importance. Pressures from climate change, population growth, diet shifts, and biofuel production raise concerns about food security. Landscape simplification due to agricultural intensification contributes to biodiversity loss, but diversification strategies can enhance ES and reduce reliance on synthetic inputs, narrowing yield gaps between conventional and more sustainable production practices. Nonetheless, policy interventions promoting diversification and low-input farming practices should be advocated. Further research is needed to fill the gaps identified in the literature.