Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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Hippophae rhamnoides L. Fruit Extract Relieves Chronic Idiopathic Constipation and Improves Bowel Function: A Monocentric, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial
Background/Objectives: Chronic idiopathic constipation (CIC) is a common gastrointestinal disorder with a global prevalence of about 14%, common in women and elderly population. It often lacks effective treatment. This randomized clinical trial was aimed to evaluate the efficacy and tolerability of Hippophae rhamnoides L. (sea buckthorn) fruit extract in adults with CIC. Methods: A UHPLC-HRMS/MS analysis was performed on the hydroethanolic H. rhamnoides fruit extract to evaluate its composition. Ninety participants were randomly assigned to receive either 500 mg of H. rhamnoides extract or placebo delivered through a capsule daily for 28 days. The primary outcome was the change in weekly spontaneous complete bowel movements (SCBMs), while secondary outcomes included stool consistency (Bristol Stool Form Scale—BSFS), gastrointestinal symptoms, and quality of life (SF-12). Results: Metabolic profile of the extract tentatively identified 75 bioactive compounds, predominantly flavonoids, triterpenoids and phospholipids. H. rhamnoides fruit extract significantly improved SCBM frequency (from 1.5 to 2.6 per week; p < 0.001) and normalized stool consistency (mean BSFS score from 1.4 to 3.5; p < 0.001), compared to no change in the placebo group. Significant reductions in bloating, abdominal pain, and heaviness were observed, while flatulence showed no between-group significant difference. No adverse events or use of rescue treatments were reported. Quality-of-life scores remained largely unchanged, with a non-significant trend towards improved mental health in the treated group. Conclusions: These findings suggest that H. rhamnoides fruit extract is a safe and effective option for managing CIC, offering an alternative to other plant extracts with laxative effects
Mapping the path to zero: 3D high-resolution spatial analysis of building energy consumption and solar generation potential in Singapore
The building sector’s substantial contribution to global energy consumption and emissions necessitates innovative approaches to achieve sustainability targets. This study develops a high-resolution spatial assessment framework for evaluating nearly zero energy building (NZEB) potential through photovoltaic (PV) integration in tropical urban environments, using Singapore as a case study. We combine top-down and bottom-up methodologies to overcome limitations of traditional 2D approaches, implementing 3D urban modelling with Rhinoceros/Grasshopper and Cyclops to accurately capture mutual shading effects and facade solar potential in high-density contexts. Using Singapore’s Building and Construction Authority energy benchmarks and Urban Redevelopment Authority building classifications, we assessed 85,197 buildings across four PV deployment scenarios. Results reveal that buildings consumed 6.21 million tons of oil equivalent, with three distinct high-consumption zones identified. PV systems could generate 20.02 TWh from rooftops and 4.27–9.97 TWh from facades annually, achieving theoretical substitution rates of 27.70–41.50 % via annual energy balance assessment. Two-stage temporal analysis using 8760-hour profiles reveals daily self-sufficiency of 26–64 % without storage, requiring 4–6 h battery capacity to bridge theoretical potential with practical viability, yielding storage-inclusive payback periods of 3.2–8.3 years. Spatial analysis at 0.3 km × 0.3 km resolution identifies central Singapore as having the highest NZEB potential, while certain areas face challenges due to high energy demands and limited solar access. Cost-benefit analysis demonstrates economic viability with payback periods of 2–3 years and net incomes of SGD 127.27-150.33 billion over 25 years. This framework provides crucial insights for urban energy planning in tropical cities, offering a replicable methodology for assessing renewable energy integration potential at the city scale
Modelling causal and multiscale network dynamics to understand complex brain functions: Application to health and disease
The human brain operates as a complex, multiscale system in which coordinated activity emerges from interactions across distributed networks. Understanding this complexity requires investigating connectivity at multiple levels such as structural, functional, and effective connectivity, which capture the brain’s architecture and function across different dimensions. Advances in computational neuroimaging have made it possible to model these dimensions using biophysically informed frameworks. Among these, Dynamic Causal Modelling (DCM) can be used to estimate directed, so called effective connectivity between brain pairs of regions, while The Virtual Brain (TVB) simulates large-scale neural activity constructed by individual structural and physiological parameters.
This thesis applies these frameworks to investigate how brain networks maintain, adapt, and reorganize their connectivity across motor, developmental, and neuroinflammatory conditions. Using DCM and TVB, this thesis explores how directed communication and excitation/inhibition balance shape healthy brain function and how their disruption contributes to pathology. In the first study, DCM was used to examine action execution (AE) and action observation (AO) to test the hypothesis that how cerebro-cerebellar loops implement sensorimotor prediction. A visuomotor network including primary motor, parietal, and cerebellar regions showed shared architecture across AE and AO, with cerebellar output switching from excitatory to inhibitory depending on task context. This revealed the cerebellum as a dynamic regulator of cortical communication and predictive control. Building on this, the second study extended the modelling framework to developmental dyslexia (DD), integrating imaging and genetic data to investigate how reading proficiency and the DCDC2-related READ1 deletion variant influence cortico-cerebellar coupling. Results showed that children with DD carrying READ1d exhibited reduced effective connectivity between the cerebellum and dorsal magnocellular and ventral attention regions, while reading proficiency was linked to stronger cerebellar modulation of visuo-attentional processes; highlighting the cerebellum’s integrative role in linking perceptual and cognitive functions. Finally, the third study combined DCM and TVB information to study the relevance of alterations in directed connectivity and excitation/inhibition dynamics for clinical measures in a cohort including people with multiple sclerosis (pwMS); This final study examined interactions using task-based, resting-state, and diffusion imaging data. Results revealed preserved overall network architecture but altered effective connectivity in pwMS compared to healthy volunteers. TVB-derived inhibitory and excitatory parameters further correlated with disability and motor performance, suggesting that maladaptive regulation of inhibitory control contributes to functional impairment.
Collectively, these studies demonstrate how computational models such as DCM and TVB can bridge local causal interactions with large-scale network dynamics, offering mechanistic insights into brain reorganization across distinct domains. By pointing towards an integration of multimodal imaging with biologically interpretable modelling, this thesis contributes to the development of multiscale, model-informed biomarkers that may guide personalized diagnosis, prognosis, and possible treatment strategies in complex brain disorders.The human brain operates as a complex, multiscale system in which coordinated activity emerges from interactions across distributed networks. Understanding this complexity requires investigating connectivity at multiple levels such as structural, functional, and effective connectivity, which capture the brain’s architecture and function across different dimensions. Advances in computational neuroimaging have made it possible to model these dimensions using biophysically informed frameworks. Among these, Dynamic Causal Modelling (DCM) can be used to estimate directed, so called effective connectivity between brain pairs of regions, while The Virtual Brain (TVB) simulates large-scale neural activity constructed by individual structural and physiological parameters.
This thesis applies these frameworks to investigate how brain networks maintain, adapt, and reorganize their connectivity across motor, developmental, and neuroinflammatory conditions. Using DCM and TVB, this thesis explores how directed communication and excitation/inhibition balance shape healthy brain function and how their disruption contributes to pathology. In the first study, DCM was used to examine action execution (AE) and action observation (AO) to test the hypothesis that how cerebro-cerebellar loops implement sensorimotor prediction. A visuomotor network including primary motor, parietal, and cerebellar regions showed shared architecture across AE and AO, with cerebellar output switching from excitatory to inhibitory depending on task context. This revealed the cerebellum as a dynamic regulator of cortical communication and predictive control. Building on this, the second study extended the modelling framework to developmental dyslexia (DD), integrating imaging and genetic data to investigate how reading proficiency and the DCDC2-related READ1 deletion variant influence cortico-cerebellar coupling. Results showed that children with DD carrying READ1d exhibited reduced effective connectivity between the cerebellum and dorsal magnocellular and ventral attention regions, while reading proficiency was linked to stronger cerebellar modulation of visuo-attentional processes; highlighting the cerebellum’s integrative role in linking perceptual and cognitive functions. Finally, the third study combined DCM and TVB information to study the relevance of alterations in directed connectivity and excitation/inhibition dynamics for clinical measures in a cohort including people with multiple sclerosis (pwMS); This final study examined interactions using task-based, resting-state, and diffusion imaging data. Results revealed preserved overall network architecture but altered effective connectivity in pwMS compared to healthy volunteers. TVB-derived inhibitory and excitatory parameters further correlated with disability and motor performance, suggesting that maladaptive regulation of inhibitory control contributes to functional impairment.
Collectively, these studies demonstrate how computational models such as DCM and TVB can bridge local causal interactions with large-scale network dynamics, offering mechanistic insights into brain reorganization across distinct domains. By pointing towards an integration of multimodal imaging with biologically interpretable modelling, this thesis contributes to the development of multiscale, model-informed biomarkers that may guide personalized diagnosis, prognosis, and possible treatment strategies in complex brain disorders
Is Arachidonic Acid Supplementation a Valuable Support in the Context of Resistance Training? A Narrative Review
Arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, serves as a metabolic precursor for prostaglandins (PGs) such as PGE2 and PGF2α, which have been implicated in the regulation of skeletal muscle adaptations to resistance exercise. On this basis, AA supplementation has been proposed as a potential ergogenic aid in resistance training, under the hypothesis that increasing endogenous AA availability through supplementation may enhance PGs synthesis, thereby potentially influencing muscle remodeling and recovery process. However, AA remains a relatively underexplored candidate. This review aimed to summarize and critically evaluate the current evidence regarding the effects of AA supplementation in the context of resistance exercise. The limited available studies provide preliminary mechanistic observations suggesting that AA supplementation may be associated with changes in muscle strength and anaerobic performance and with modulation of the acute inflammatory response to exercise, without affecting chronic inflammation. Conversely, findings related to body composition and muscle hypertrophy remain inconsistent and a significant effect has not been consistently observed. Despite these preliminary insights, the current body of evidence is insufficient and heterogeneous, precluding the recommendation of routine clinical or practice-based use. Future well-designed, long-term investigations are warranted to clarify the efficacy, optimal dosage, and timing of AA supplementation, as well as its safety profile and potential applications across populations differing in age, sex, nutritional status, and training background
(Mis)perceptions of individual position in national and global income distribution. The Italian case
This study investigates income rank (mis)perceptions in Italy, focusing on
the discrepancy between individuals’ subjective assessments of their income
position and their objectively measured positions in national and global income
distribution. The research utilizes data from a large-scale national survey
Inequality between reality and perception (IneqPer, n = 12,000; 2024/2025).
It provides consistent evidence of the pervasive central tendency bias, when
individuals place themselves near to the median of income distribution regardless
of their objective income rank. The findings also reveal systematic patterns of
misperceptions. Lower-resource individuals tend to overestimate their income
rank, while higher-resource individuals often underestimate it. Misperceptions
vary significantly by gender, age, employment status, education, migration
background, the type of settlement, and regional economic conditions: young,
unemployed, and immigrants are more prone to overestimate their rank in
income distribution, while men, older, employed, those from urban areas
and more educated individuals are more likely to underestimate it. Political
orientation shows no associations with misperceptions of national income
rank, but left-oriented respondents are more accurate with respect to global
ranks, whereas all other respondents underestimate their global rank. Regionally,
residents of less affluent Southern areas tend to overestimate their income rank,
whereas those in wealthier Northern regions often underestimate it. The study is
one of the first that analyses both national and global income rank perceptions.
The results show that central tendency bias emerges consistently across different
contexts, suggesting that income distributions are broadly perceived as abstract.
These insights have implications for public policy, economic behavior, and
interventions addressing inequality in Italy and in the world
The loss of DDB2-PCNA interaction influences cell growth and genome stability in UV irradiated human cell
Reticulocytes and Their Maturation
Reticulocyte maturation represents the final stage of erythropoiesis and is often perceived as a straightforward transition culminating in the production of a mature red blood cell (RBC). However, this process is far more complex than traditionally assumed, with multiple unresolved mechanistic aspects. While molecular characterization of reticulocytes has significantly advanced through transcriptomic and proteomic approaches, the precise sequence of events leading to membrane remodeling, cytoskeletal maturation, and functional adaptation remains poorly understood.
A key challenge in studying reticulocyte maturation lies in distinguish-ing between different stages of reticulocyte development. The transition from marrow reticulocyte to circulating reticulocyte represents a fundamental, yet mechanistically obscure, event. Although many studies have relied on stress reticulocytes or in vitro models, these do not fully capture the physiological maturation pathway of normal circulating reticulocytes.
Among the most overlooked aspects of reticulocyte maturation is the role of membrane lipid remodeling. Unlike membrane proteins, which are largely retained or progressively lost, reticulocyte lipid composition undergoes selective and dynamic changes, likely involving phospholipid exchange with plasma lipoproteins. Recent findings suggest that phosphatidylcholine, phos-phatidylethanolamine, and sphingomyelin species are differentially remodeled, potentially influencing membrane transport properties, RBC deformability, and interactions with the membrane skeleton.
This chapter explores the coordinated regulation of membrane and volume reduction during reticulocyte maturation, which ensures the maintenance of a stable surface-to-volume ratio and prevents detrimental morphological changes. It also examines the emerging role of lipid-dependent regulation of membrane transporters, an area that remains almost entirely unexplored. The discussion extends to the possible involvement of external factors, including the spleen and liver, in reticulocyte conditioning, as well as the potential role of lipid transfer proteins such as VPS13A in RBC lipid homeostasis.
By integrating molecular and biophysical perspectives, this chapter highlights the fundamental role of membrane lipids in the transition from reticulocyte to mature RBC and proposes new directions for research in erythropoiesis, lipid remodeling, and membrane homeostasis
GIS-Based Accessibility and Safety Assessment in Small Historic Centres in Inner Areas. Pilot Application in Stigliano and Interoperability with a Digital Twin.
The high vulnerability and exposure to environmental risk of most historic villages in Italian inland areas, together with the poor accessibility, the degradation imposed by abandonment, and the increase in the elderly population, make interventions for the functional rehabilitation or reconversion of the built heritage and related public space complex and controversial. This opens questions also with respect to the evaluation and identification of possible actions to improve territorial and local accessibility emphasizing the need to consider among the priority the redevelopment, transformation and securing of the public space. Within this framework, the article experiments with a possible decision-supporting evaluation process in the minor historic center of Stigliano (MT), the lead municipality of the inner area Montagna Materana and currently the site of an experimental inter-university research project on digital twin implementation. The contribution gives a first reading of information collected through digital survey and GIS-based collaborative data collection techniques and set up a methodology to plan and prioritise interventions aimed at improving accessibility and safety. The methodology is based on a set of indicators for evaluating usability, walkability, and vulnerability. The objective is twofold: on the one hand, to ensure accessibility and safety of the routes that provide access to services and relational nodes within the historic center, with particular attention to daily use and the most fragile users; on the other hand, to make tourist usability more attractive, comfortable and inclusive
Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases
Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cells are central mediators of both disease initiation and progression. Astrocytes, microglia, and oligodendrocyte lineage cells modulate neuronal survival by regulating neuroinflammation, metabolic support, synaptic maintenance, and proteostasis. However, dysregulated glial responses, including chronic microglial activation, impaired phagocytosis, altered cytokine production, and mitochondrial dysfunction, contribute to persistent inflammation and structural degeneration observed across Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes current knowledge regarding the multifaceted involvement of glial cells in neurodegenerative disorders
Thematic analysis of a suicide note revealing a possible and undiagnosed dissociative identity disorder: a case report
This study analysed a suicide case involving a potential dissociative
identity disorder (DID) through the analysis of a suicide note and
two additional handwritten notes. These were found during the
death scene investigation of a hanging case of a woman as part of
the judicial investigation, including autopsy and toxicological
examination. Each of the notes was preceded by the name of the
deceased, followed by a number (for example, Giulia 1 and Giulia 2;
fictional names). It was reported in the deceased’s clinical history
the presence of unidentified psychological disorders. We employed
a discourse analysis of these texts. Eight main themes emerged
from the in-depth analysis, expressing the possibility of a DID. The
themes were divided into Giulia 1 (who wants to live) and Giulia 2
(who wants to commit suicide). Our study highlights the complexity
of suicidal behaviour in patients with DID, underscoring the relevance
of early diagnosis and treatment to prevent suicide. Suicidal
notes, which are relevant for forensic investigation, may also be
useful for clinical aims, including the development of preventive
strategies to reduce suicide rates among this population