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Rosaria Di Lorenzo,1 Anita Iorio,2 Margherita Pinelli,3 Federica Magarini,3 Mattia Marchi,3 Andrea Sacchetti,3 Chiara Calogero,4 Gian Maria Galeazzi,5 Paola Ferri,5 Sergio Rovesti,5 Alessandro Minarini6 1Service of Psychiatric Diagnosis and Care, Department of Mental Health and Pathological Addictions, AUSL-Modena, Modena, Italy; 2Psychiatric Rehabilitation Technique Programme, University of Modena and Reggio Emilia, Reggio Emilia, Italy; 3School of Psychiatry, University of Modena and Reggio Emilia, Modena, Italy; 4Community Mental Health Center, Vignola (MO), Department of Mental Health and Pathological Addictions, AUSL-Modena, Modena, Italy; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 6Community Mental Health Center, Vignola (MO), Department of Mental Health and Pathological Addictions, AUSL-Modena, Modena, MO, ItalyCorrespondence: Rosaria Di Lorenzo, Department of Mental Health and Pathological Addictions, AUSL-Modena, Service of Psychiatric Diagnosis and Care, via P. Giardini n. 1355, Baggiovara (MO), 41126, Italy, Email r.dilorenzo@ausl.mo.itPurpose: Antipsychotic long-acting injections (AP-LAIs) are indicated for patients affected by schizophrenia especially those with poor treatment adherence.Patients and Methods: To compare paliperidone palmitate 3-monthly (PP3M), paliperidone palmitate one-monthly (PP1M) and haloperidol decanoate (HAL-D) treatment, we enrolled 90 patients with schizophrenia treated in Mental Health Center with one of the three AP-LAIs for at least six months and followed them for another 6 months. At 6 and 12 months of treatment we administered Clinical Global Impression-Severity, Global Assessment of Functioning and World Health Organization Quality of Life-26 items (WHOQOL-BREF). At 1-year treatment, we evaluated relapses (psychiatric hospitalizations and urgent consultations), side effects and drop-outs.Results: We did not highlight any statistically significant difference among the three treatments in relapses and scale scores. Weight increase was significantly higher in PP1M and PP3M groups. Twelve patients (13.3%) discontinued AP-LAI. At 1-year AP-LAI treatment, 69% of patients rated quality of life as “good” or “very good” and 71% declared themselves to be “satisfied” or “very satisfied”.Conclusion: HAL-D, PP1M and PP3M 1-year treatments were similarly effective in preventing relapses and improving quality of life and health satisfaction. All discontinuations in the new 3-monthly antipsychotic treatment were caused by patient refusal to continue it.Keywords: antipsychotic long-acting injections, schizophrenia spectrum disorders, relapses, quality of life, health satisfaction

Plasmonic nanoparticles (NPs) are exploited to concentrate light, provide local heating and enhance drug release when coupled to smart polymers. However, the role of NP assembling in these processes is poorly investigated, although their superior performance as nanoheaters has been theoretically predicted since a decade. Here we report on a compound hydrogel (agarose and carbomer 974P) loaded with gold NPs of different configurations. We investigate the dynamics of light-heat conversion in these hybrid plasmonic nanomaterials via a combination of ultrafast pump-probe spectroscopy and hot-electrons dynamical modeling. The photothermal study ascertains the possibility to control the degree of assembling via surface functionalization of the NPs, thus enabling a tuning of the photothermal response of the plasmon-enhanced gel under continuous wave excitation. We exploit these assemblies to enhance photothermal release of drug mimetics with large steric hindrance loaded in the hydrogel. Using compounds with an effective hydrodynamic diameter bigger than the mesh size of the gel matrix, we find that the nanoheaters assemblies enable a two orders of magnitude faster cumulative drug release toward the surrounding environment compared to isolated NPs, under the same experimental conditions. Our results pave the way for a new paradigm of nanoplasmonic control over drug release.

Abstract Geographic distribution, as well as evolutionary and biogeographic processes and patterns of marine invertebrate benthic species are strongly shaped by dispersal ability during the life cycle. Remote oceanic islands lie at the brink of complex biotic and abiotic interactions which have significantly influenced the biodiversity patterns we see today. The interaction between geological environmental change and taxon-specific dispersal modes can influence species evolutionary patterns, eventually delimiting species-specific biogeographic regions. In this study, we compare the population genetic patterns of the marine bivalve Cardita calyculata in the northeast Atlantic, discussing the role of Macaronesian islands during past climatic cycles. The genetic structure and diversity patterns were outlined based on SSR-GBAS loci of 165 individuals and on the mitochondrial COI marker of 22 individuals from the Canary Islands, Madeira, Azores and the Mediterranean. The highly structured genetic pattern found among regions and within archipelagos suggests the central role of oceanic islands in promoting the divergence of the species in both the NE Atlantic and the Mediterranean. The high degree of divergence in the COI dataset (> 7%) suggests the existence of potential cryptic speciation that needs to be further explored with a more comprehensive sampling. Such patterns are only congruent with a scenario where C. calyculata populations were maintained during glacial/interglacial cycles, supporting the role of the studied archipelagos as drivers of diversity for marine biota. We stress the importance of developing studies for species with various life history and dispersal modes. In such a way, a more profound understanding of the biogeographic and evolutionary significance of oceanic islands can catalyse directed conservation efforts, especially in the context of the ongoing climate crisis.

Abstract Generalizing defensive responses to new stimuli resembling learned threats is an adaptive process within an ever-changing environment. However, evaluation mechanisms excessively biased toward generalization (i.e., overgeneralization) may underlie anxiety-related symptoms. In the context of obesity, fear memory and fear generalization processes have never been investigated. In this study, participants with obesity and healthy participants as controls underwent a single-cue auditory fear conditioning paradigm and recognition memory tasks. We analyzed the autonomic reactions evoked by threat-predictive and new stimuli, as well as the recognition performance towards the same cues. We found that participants with obesity displayed similar autonomic defensive responses to a learned fearful stimulus, but enhanced reactions to new stimuli, when compared with the controls. We detected no significant differences between groups in recognition abilities. Our results provided the first evidence that obesity may widen fear generalization patterns. This alteration may encourage future research in investigating the link between emotional dysregulation and clinical anxiety-related symptoms in obesity.

For a long time, the leather industry has considered the chromium tanning process to be the easiest and fastest way to treat raw hides and transform them into valuable products. In the last few decades, increasing attention has been paid to the potential oxidation of the trivalent chromium in tanned leather. This happens for many reasons, such as the quality of the tanning agent or the adoption of good manufacturing practices. Anyway, the main problem, which is difficult to solve, is the sensibility of the free residual chromium tanned leather, which is high enough for possible harmful activity. Given this scenario, this work proposes a solution to decrease hexavalent chromium formation by using antioxidants during the leather tanning process. In this regard, a screening work was started, to find the worst-case scenario for trivalent chromium oxidation. To do this, commercial tanning products were employed, especially fatliquoring agents, which, in some cases, are the main source that could easily react with ROS (Reactive Oxygen Species) to drive chromium oxidation. After the determination of conditions, different groups of common antioxidants were tested to analyse the antioxidation performances and their possible use in the chromium-based tanning process. The results underline the efficient action of the antioxidants studied, paving the way for some interesting perspectives to limit the drawbacks of chromium tanned leather.

World university rankings have had an impact on academic competition worldwide. The comparability of ranking results depends on how data is collected within each university. When data concepts are interpreted differently, data variety is introduced and ranking results cannot be used in a meaningful manner. In this case study, the effect of semantic harmonisation of the data concepts of the "Times Higher Education" World University Ranking is evaluated. Based on two independent initiatives, in Italy and in Belgium, the data and results of this ranking before and after interuniversity harmonisation of data collection are compared. This study demonstrates that, despite the data definitions provided by the ranking organisation, the data concepts 'academic staff' and 'students' are interpreted differently within each university. These differences can affect how universities are positioned relative to each other in ranking tables. A profound level of semantic harmonisation is then required to ensure semantically comparable data.

Background: Cemented total knee arthroplasty (TKA) is the gold standard treatment for osteoarthritis, but uncemented TKA offers benefits like improved osseointegration and reduced complications from cement debris. This study aimed to investigate (1) if there has been a rise in uncemented TKA from 2017 to 2021 and (2) if there are differences in early complications between cemented and uncemented TKA. Methods: A retrospective data review was performed on the Michigan Arthroplasty Registry Collaborative Quality Initiative database of TKA patients from 2017 to 2021 at 6 hospitals. Patients with revision or partial knee arthroplasty were excluded. Patients were divided into 2 groups: uncemented and cemented. Hybrid and reverse hybrid fixation data were collected for incidence, but not for demographics or complications. All patient demographics and 90-day postoperative events were collected and analyzed. Results: A retrospective study of 18,749 primary TKAs found that 89.7% were cemented, 9.7% uncemented, and 0.7% hybrid or reverse hybrid. Uncemented patients were younger, men, heavier, current smokers, and diabetics than cemented patients (P < .0001, P = .03). They also had a shorter length of stay (P ≤ .0001) and were on fewer preoperative medications: anticoagulants (P = .0059), antiplatelets (P ≤ .0001), opioids (P = .0091), and steroids (P = .0039). The rate of uncemented TKA increased from 3.3% to 17.1%, while the rate of cemented TKA fell from 96.2% to 81.9% (P = .0048). The readmission rate was higher in cemented TKAs (4.0%) than in uncemented TKAs (2.6%) (P = .0048). Conclusions: The use of uncemented TKA increased from 3.3% in 2017 to 17.1% in 2021, while cemented fixation decreased from 96.7% to 81.9%. There were no significant differences in short-term complications between groups. Uncemented patients were younger, men, took fewer medications, had a shorter length of stay, and were less likely to be readmitted. However, they were more likely to have comorbidities than the cemented group.

Summary: Intra-tumor heterogeneity, i.e., the presence of diverse cell types and subpopulations within tumors, presents a significant obstacle in cancer treatment due to its negative consequences for resistance to therapy and disease recurrence. However, the mechanisms that underlie intra-tumor heterogeneity and result in the plethora of different cancer cells within a single lesion remain poorly understood. Here, we leverage the SW480 cell line as a model system to investigate the molecular and functional diversity of colon cancer cells. Through a combination of fluorescence-activated cell sorting (FACS) analysis and transcriptomic profiling, we identified three distinct subpopulations, namely resident cancer stem cells (rCSCs), migratory CSCs (mCSCs), and high-relapse cells (HRCs). These subpopulations show varying Wnt signaling levels and gene expression profiles mirroring their stem-like and functional properties. Examination of publicly available spatial transcriptomic data confirms the presence of these subpopulations in patient-derived cancers and reveals their distinct spatial distribution relative to the tumor microenvironment.

Background: The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation. Objective: To evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [18F]FDG-PET measures of neural dysfunction. Methods: We retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [18F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [18F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC). Results: Based on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [18F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC. Conclusion: This study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.

Complex fistulizing perianal disease is a disabling manifestation of inflammatory bowel disease (IBD), seriously compromising patients ‘quality of life’. The success rate of available treatments is quite low, and nearly half of the patients will develop chronically active fistulas or experience fistula recurrence. Mesenchymal stem cell therapy has shown interesting results, but the complexity and the cost of production limit its widespread use. This study aims to report the results of the innovative use of autologous emulsified adipose-derived stromal vascular fraction tissue for treating complex fistulizing perianal disease. From March 2021 to March 2022, 10 patients underwent a two-step procedure: (1) examination under anaesthesia, with loose seton drainage and 4 weeks later and (2) curettage of the fistulous tract, internal fistula closure and an injection of autologous emulsified adipose-derived stromal vascular fraction tissue harvested from the subcutaneous layer of the patient’s hip. Clinical and radiological (through magnetic resonance imaging) healing were assessed at 6 months. We included five patients affected by Crohn’s disease, three by ulcerative colitis and two by indeterminate colitis. All patients were on concomitant biological therapy (50% on Infliximab). One patient required a re-treatment for a relapse and two different fistulas were separately treated in another one. Out of 12 total procedures performed, clinical healing was achieved in 10 cases (83%), while radiological healing in 6 patients (50%). No adverse events were recorded. Autologous emulsified adipose-derived stromal vascular fraction tissue can represent an effective, safe and cheap add-on therapy for patients with complex perianal fistulas in IBDs.

A partir de uma pesquisa em Design que desenvolve uma interface digital direcionada ao ensino acadêmico de Design de Moda, este artigo traz um desdobramento de sua componente exploratória. O objetivo deste artigo é analisar como estudantes de Design de Moda da Universidade Estadual de Londrina consomem conteúdo de Moda para identificar oportunidades para os meios digitais de comunicação de forma a complementar o ensino universitário e prepará-los para o mercado profissional. O método da pesquisa parte de revisão de literatura sobre a evolução da comunicação de Moda desde o início até seu contexto atual e aplicação de questionário com estudantes e entrevistas com professoras. São selecionadas respostas do primeiro e quarto ano para comparação e os principais comentários das entrevistas para sustentar a discussão sobre as questões mais importantes observadas. Por fim é discutido como a comunicação entre professores e estudantes e o percurso acadêmico podem influenciar na procura por informação de Moda pelos estudantes. O artigo tem como resultado a ampliação de perspectivas e possibilidades para as mídias digitais de comunicação de Moda com recursos educativos que complementam o ensino universitário e auxiliam os estudantes no complexo sistema profissional de Moda.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.

Abstract Traditional fully-deterministic algorithms, which rely on physical equations and mathematical models, are the backbone of many scientific disciplines for decades. These algorithms are based on well-established principles and laws of physics, enabling a systematic and predictable approach to problem-solving. On the other hand, AI-based strategies emerge as a powerful tool for handling vast amounts of data and extracting patterns and relationships that might be challenging to identify through traditional algorithms. Here, we bridge these two realms by using AI to find an optimal mapping of meteorological features predicted two days ahead by the state-of-the-art numerical weather prediction model by the European Centre for Medium-range Weather Forecasts (ECMWF) into lightning flash occurrence. The prediction capability of the resulting AI-enhanced algorithm turns out to be significantly higher than that of the fully-deterministic algorithm employed in the ECMWF model. A remarkable Recall peak of about 95% within the 0-24 h forecast interval is obtained. This performance surpasses the 85% achieved by the ECMWF model at the same Precision of the AI algorithm.

Over the past three years, the international debate on architecture and design has been deeply influenced by various crises, including health, environmental, social, and economic emergencies. In this dynamic, post-pandemic context, the integration of new technologies into domestic spaces through personal devices has profoundly altered the way these spaces are utilized. From the initial impact of television screens and computers to the contemporary intrusion of social networks, video games, and artificial intelligence, interiors are constantly evolving and adapting to technological advancements that redefine their functional boundaries. The notion of Post-Domesticity, as introduced by philosopher Paul B. Preciado in his work Pornotopia. An Essay on Playboy’s Architecture and Biopolitics (2014), serves as a precursor to the current scenario marked by the erasure of boundaries between public and private spheres.

Motor deficit is a core symptom of Rett syndrome, a rare neurological disease caused in most cases by mutations of the methyl-CpG-binding protein2 (MECP2) gene. Serotonin reuptake inhibitors improve motor coordination in Mecp2 heterozygous (Het) mice and serotonin depletion prevented this effect. Here, we assess alterations in indole levels in various brain regions and whether boosting brain serotonin synthesis with the serotonin precursors tryptophan, 5-hydroxytryptophan and α-lactalbumin rescued motor coordination deficit of Mecp2 Het mice. Motor coordination was assessed in the accelerated rotarod during and after systemic administration of serotonin precursors for 2–3 weeks. Since no data are available, the effect of α-lactalbumin on tryptophan, serotonin and 5-hydroxyindoleacetic acid levels was evaluated in various brain regions in order to identify the dose of ALAC to evaluate on motor coordination. As compared to WT, Mecp2 Het mice show reduced levels of serotonin in the whole brain, hippocampus, brainstem and cerebral cortex, but not the striatum. Reduced levels of 5-hydroxyindoleacetic acid were observed in the hippocampus and brainstem. Doses of serotonin precursors increasing brain tryptophan and/or serotonin production and metabolism had no effect on motor coordination. The results indicate that boosting serotonin synthesis is not sufficient to improve motor coordination of Mecp2 Het mice.

Severe adult-acquired flatfoot deformity is widely addressed surgically via the Grice–Green subtalar arthrodesis. Standard radiographic measurements have been reported, but these are limited to planar views. These complex deformities and the relevant corrections after surgery should be assessed in weight-bearing using 3D analyses now enabled by modern cone-beam CT scans. The present study is aimed at reporting these 3D radiographical foot bone alignments and the clinical results for this surgery. Ten patients were treated with the Grice–Green procedure. This implies inserting an autologous bone graft from the proximal tibial into the extra-articular sinus-tarsi to perform a subtalar arthrodesis. Before and after surgery, the patients were assessed based on the clinical range-of-motion and Foot-Function and Posture Indexes. Three-dimensional models of the tibia, calcaneus, talus, navicular, and 1st metatarsus were reconstructed from cone-beam CT scans in a single-leg up-right posture. Relevant longitudinal axes were defined to calculate ten spatial angles. Post-operatively, a significant realignment was observed for seven angles, including corrections lift-up of the talus (on average by 15°) and subtalar joint (13° in 3D), as well as the Meary’s angle (21°). Only few correlations were found between traditional clinical and novel 3D radiographical measurements, suggesting the former only limitedly represent the corresponding real skeletal status, and the latter thus offer the physician a more comprehensive evaluation. The present original analysis from modern cone-beam CT scans shows precisely the correction of foot and ankle bone alignments achieved using the Grice–Green surgical procedure, finally in 3D and in weight-bearing. For the first time, traditional clinical and score system evaluations are reported together with bone orientation and joint angles in the three anatomical planes.

BackgroundCurrent guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes.MethodsThree-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer.ResultsThroughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers.ConclusionA behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

Summary: The mammalian brain can store and retrieve memories of related events as distinct memories and remember common features of those experiences. How it computes this function remains elusive. Here, we show in rats that recent memories of two closely timed auditory fear events share overlapping neuronal ensembles in the basolateral amygdala (BLA) and are functionally linked. However, remote memories have reduced neuronal overlap and are functionally independent. The activity of parvalbumin (PV)-expressing neurons in the BLA plays a crucial role in forming separate remote memories. Chemogenetic blockade of PV preserves individual remote memories but prevents their segregation, resulting in reciprocal associations. The hippocampus drives this process through specific excitatory connections with BLA GABAergic interneurons. These findings provide insights into the neuronal mechanisms that minimize the overlap between distinct remote memories and enable the retrieval of related memories separately.

The lack of affordable and effective therapeutics against cognitive impairment has promoted research toward alternative approaches to the treatment of neurodegeneration. In recent years, a bidirectional pathway that allows the gut to communicate with the central nervous system has been recognized as the gut-brain axis. Alterations in the gut microbiota, a dynamic population of trillions of microorganisms residing in the gastrointestinal tract, have been implicated in a variety of pathological states, including neurodegenerative disorders such as Alzheimer’s disease (AD). However, probiotic treatment as an affordable and accessible adjuvant therapy for the correction of dysbiosis in AD has not been thoroughly explored. Here, we sought to correct the dysbiosis in an AD mouse model with probiotic supplementation, with the intent of exploring its effects on disease progression. Transgenic 3xTg-AD mice were fed a control or a probiotic diet (Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601) for 12 weeks, with the latter leading to a significant increase in the relative abundance of Bacteroidetes. Cognitive functions were evaluated via Barnes Maze trials and improvements in memory performance were detected in probiotic-fed AD mice. Neural tissue analysis of the entorhinal cortex and hippocampus of 10-month-old 3xTg-AD mice demonstrated that astrocytic and microglial densities were reduced in AD mice supplemented with a probiotic diet, with changes more pronounced in probiotic-fed female mice. In addition, elevated numbers of neurons in the hippocampus of probiotic-fed 3xTg-AD mice suggested neuroprotection induced by probiotic supplementation. Our results suggest that probiotic supplementation could be effective in delaying or mitigating early stages of neurodegeneration in the 3xTg-AD animal model. It is vital to explore new possibilities for palliative care for neurodegeneration, and probiotic supplementation could provide an inexpensive and easily implemented adjuvant clinical treatment for AD.