Therapeutic induction of energy metabolism reduces neural tissue damage and increases microglia activation in severe spinal cord injury.

Neural tissue has high metabolic requirements. Following spinal cord injury (SCI), the damaged tissue suffers from a severe metabolic impairment, which aggravates axonal degeneration and neuronal loss. Impaired cellular energetic, tricarboxylic acid (TCA) cycle and oxidative phosphorylation metabolism in neuronal cells has been demonstrated to be a major cause of neural tissue death and regeneration failure following SCI. Therefore, rewiring the spinal cord cell metabolism may be an innovative therapeutic strategy for the treatment of SCI. In this study, we evaluated the therapeutic effect of the recovery of oxidative metabolism in a mouse model of severe contusive SCI. Oral administration of TCA cycle intermediates, co-factors, essential amino acids, and branched-chain amino acids was started 3 days post-injury and continued until the end of the experimental procedures. Metabolomic, immunohistological, and biochemical analyses were performed on the injured spinal cord sections. Administration of metabolic precursors enhanced spinal cord oxidative metabolism. In line with this metabolic shift, we observed the activation of the mTORC1 anabolic pathway, the increase in mitochondrial mass, and ROS defense which effectively prevented the injury-induced neural cell apoptosis in treated animals. Consistently, we found more choline acetyltransferase (ChAT)-expressing motor neurons and increased neurofilament-positive corticospinal axons in the spinal cord parenchyma of the treated mice. Interestingly, oral administration of the metabolic precursors increased the number of activated microglia expressing the CD206 marker suggestive of a pro-resolutive, M2-like phenotype. These molecular and histological modifications observed in treated animals ultimately led to a significant, although partial, improvement of the motor functions. Our data demonstrate that rewiring the cellular metabolism can represent an effective strategy to treat SCI.

A Hotspot of TTX Contamination in the Adriatic Sea: Study on the Origin and Causative Factors.

Tetrodotoxins (TTXs), the pufferfish venom traditionally associated with Indo-Pacific area, has been reported during last decades in ever wider range of marine organisms and ever more geographical areas, including shellfish in Europe. Wild mussels (Mytilus galloprovincialis) grown in the Marche Region (N Adriatic Sea, Italy) were shown to be prone to TTX contamination during the warm season, with a suspected role of Vibrio alginolyticus characterized by non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS)-encoding genes. This work aimed to deepen the knowledge about the toxin's origin and the way through which it accumulates in mussels. A two-year study (spring-summer 2020-2021) confirmed the recurrent presence of TTX (11-68 µg kg-1) in the official monitored natural mussel beds of the Conero Riviera. During 2021, a supplementary nonroutine monitoring of a natural mussel bed in the same area was carried out weekly from June until August for TTXs and/or the presence of V. alginolyticus. Biotic (mussels, mesozooplankton, worms and phytoplankton); abiotic (water and sediment) matrices and phytoplankton assemblage characterizations were studied. Mussels showed relevant TTX contamination levels (9-296 µg kg-1) with extremely rapid TTX accumulation/depletion rates. The toxin presence in phytoplankton and its distribution in the different mussel tissues supports its possible exogenous origin. The V. alginolyticus count trend overlaps that of TTX contamination in mussels, and similar trends were reported also for some phytoplankton species. The role of V. alginolyticus carrying NRPS or PKS genes as a possible TTX source and of phytoplankton as a "potential vector" should therefore be further investigated.

Water quality integrated system: A strategic approach to improve bathing water management.

In the Adriatic Sea, massive rainfall events are causing flooding of rivers and streams, with severe consequences on the environment. The consequent bacterial contamination of bathing water poses public health risks besides damaging tourism and the economy. This study was conducted in the framework of WATERCARE, an EU Interreg Italy-Croatia Project, which aims at reducing the impact of microbial contamination on Adriatic bathing water due to heavy rainfall events drained in the local sewage network and; enhancing the quality of local waters; and providing support for the decision-making processes regarding the management of bathing water in line with EU regulations. The study involved the development of an innovative water quality integrated system that helps meet these objectives. It consists of four components: a real time hydro-meteorological monitoring system; an autosampler to collect freshwater samples during and after significant rainfall events; a forecast system to simulate the dispersion of pollutants in seawater; and a real-time alert system that can predict the potential ecological risk from the microbial contamination of seawater. The system was developed and tested at a pilot site (Fano, Italy). These preliminary results will be used to develop guidelines for urban wastewater and coastal system quality assessments to contribute to develop policy actions and final governance decisions.

Psychosis of Alzheimer's disease: Neuropsychological and neuroimaging longitudinal study.

OBJECTIVES: Psychosis of Alzheimer's disease (AD) may represent a distinct disease phenotype; however, neuropsychological profile and neural basis linked to this phenotype have not yet been clarified. In this study, we aimed at detecting whether impairment in specific cognitive domains predicts the onset of psychosis in AD patients and what grey matter alterations, their location, and the rate of atrophy are associated with psychosis of AD. METHODS: Longitudinal neuropsychological data from AD patients with and without psychosis were analysed to determine whether the neuropsychological profile can predict the onset of psychosis. A voxel-based morphometry (VBM) on longitudinal T1-weighted images was used to explore differences in grey matter volume and in the rate of atrophy between groups. RESULTS: Noncognitive domain predicted the psychosis onset. However, AD patients with psychosis exhibited greater atrophy in the right anterior-inferior temporal lobe, including the fusiform gyrus (cluster-p-family-wise error [pfwe] < 0.05; peak-p uncorrected [pUNC] < 0.001) as well as greater rate of atrophy in the right insula than nonpsychotic patients (cluster-pFWE = 0.075; peak-pUNC < 0.001). The anterior-inferior temporal lobe is part of the ventral visual stream, and the insula plays a key role in the salience network. CONCLUSIONS: This finding suggests that damage in these areas underpins an impairment in the visual processing of the objects and an impairment in the attribution of salience to the misperceived stimuli, which in turn leads to the onset of psychosis. These findings tie in well with the neuropsychological model of psychosis, according to which the simultaneous presence of two factors, namely misperception and misattribution, underlies psychosis in dementia.

Attenuation of Choroidal Thickness in Patients With Alzheimer Disease: Evidence From an Italian Prospective Study.

INTRODUCTION: To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. METHODS: In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. RESULTS: After 12 months, AD patients had a greater reduction of CT than controls (P≤0.05, adjusted for baseline CT, age, sex, axial length, and smoking). DISCUSSION: CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging.

A methodology to assess the accuracy with which remote data characterize a specific surface, as a function of Full Width at Half Maximum (FWHM): application to three Italian coastal waters.

This methodology assesses the accuracy with which remote data characterizes a surface, as a function of Full Width at Half Maximum (FWHM). The purpose is to identify the best remote data that improves the characterization of a surface, evaluating the number of bands in the spectral range. The first step creates an accurate dataset of remote simulated data, using in situ hyperspectral reflectances. The second step evaluates the capability of remote simulated data to characterize this surface. The spectral similarity measurements, which are obtained using classifiers, provide this capability. The third step examines the precision of this capability. The assumption is that in situ hyperspectral reflectances are considered the "real" reflectances. They are resized with the same spectral range of the remote data. The spectral similarity measurements which are obtained from "real" resized reflectances, are considered "real" measurements. Therefore, the quantity and magnitude of "errors" (i.e., differences between spectral similarity measurements obtained from "real" resized reflectances and from remote data) provide the accuracy as a function of FWHM. This methodology was applied to evaluate the accuracy with which CHRIS-mode1, CHRIS-mode2, Landsat5-TM, MIVIS and PRISMA data characterize three coastal waters. Their mean values of uncertainty are 1.59%, 3.79%, 7.75%, 3.15% and 1.18%, respectively.

Variability of hydrographic and biogeochemical properties in the North-western Adriatic coastal waters in relation to river discharge and climate changes.

The dynamics of hydrographic and biogeochemical properties in a Northwestern coastal area of the Adriatic Sea were investigated. The time series data from continuous observation (2007-2022) allowed the investigation of annual trends and seasonal cycles along a coastal transect influenced by local river discharge. Various statistical models were used to investigate water temperature, salinity, chlorophyll a, dissolved organic, inorganic and particulate nutrients, precipitation and river discharge. It was found that the local river discharge regime played an essential role in interannual, and seasonal biogeochemical dynamics associated with global climate change in the Mediterranean region. A significant trend towards oligotrophic conditions was detected, as evidenced by the downward trend in the river mouth and on the sea of chlorophyll a (-0.2 µg L-1 in the sea), dissolved organic and inorganic nitrogen and phosphorus (i.e., -0.43 µM yr-1 of DON in the sea and -6.67 of DIN µM yr-1 in the river mouth or -0.07 µM yr-1 of DOP and -0.02 µM yr-1 of DIP in the river mouth) and silicate (-2.47 µM yr-1 in the river mouth) concentrations. Salinity showed a long-term increase in the sea (0.08 yr-1), corresponding to a significant decrease in water discharge from the local river (-0.27 m3 s-1 yr-1) and precipitation (-0.06 mm yr-1). The dissolved organic and inorganic nutrients highlighted a different seasonal accumulation under the river runoff regime. The nutrient enrichment was predominantly driven by river contribution. Data analysis showed that the coastal biogeochemical properties dynamics were mostly influenced by river discharge and precipitation regimes, which in turn are driven by climate change variability in the North-western Adriatic Sea.

Generation of mouse hippocampal brain organoids from primary embryonic neural stem cells.

Here we present a protocol to generate standardized cerebral organoids with hippocampal regional specification using morphogen WNT3a. We describe steps for isolating mouse embryonic (E14.5) neural stem cells from the brain subgranular zone, preparing organoids samples for immunofluorescence, calcium imaging, and metabolic profiling. This protocol can be used to generate mouse brain organoids for developmental studies, modeling disease, and drug screening. Organoids can be obtained in one month, thus providing a rapid tool for high-throughput data validation. For complete details on the use and execution of this protocol, please refer to Ciarpella et al. "Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity".1.

Sundowning in Patients with Dementia: Identification, Prevalence, and Clinical Correlates.

BACKGROUND: The term sundowning is used to describe the emergence or worsening of neuropsychiatric symptoms in late afternoon or early evening in people with dementia. OBJECTIVE: Our aim was to evaluate sundowning's prevalence and clinical manifestations among patients attending a tertiary memory clinic and to investigate its clinical and neuropsychological correlates. METHODS: Patients with dementia attending our memory clinic were enrolled in the study. Sundowning was identified through a specifically designed questionnaire. Sociodemographic and clinical features of sundowners and non-sundowners were compared, and a logistic regression was performed to identify the variables associated with the phenomenon. A subgroup of patients underwent a complete neuropsychological assessment. RESULTS: Among 184 recruited patients, 39 (21.2%) exhibited sundowning, mostly expressed as agitation (56.4%), irritability (53.8%), and anxiety (46.2%). Sundowners were significantly older, had a later dementia onset, exhibited more severe cognitive and functional impairment, more frequent nocturnal awakenings, and hearing loss relative to non-sundowners. They were also more likely to use anticholinergic medications and antipsychotics, and less likely to use memantine. In a multi-adjusted model, the factors significantly associated with sundowning were the Clinical Dementia Rating score (OR 3.88; 95% CI 1.39-10.90) and the use of memantine (OR 0.20; 95% CI 0.05-0.74). Participants with and without sundowning obtained similar results in single domain neuropsychological tests. CONCLUSION: Sundowning is commonly experienced by patients with dementia and appears as a multiply determined condition. Its presence should always be evaluated in clinical practice and a multidimensional approach should be adopted to identify its predictors.

Acclimatization of a coral-dinoflagellate mutualism at a CO2 vent.

Ocean acidification caused by shifts in ocean carbonate chemistry resulting from increased atmospheric CO2 concentrations is threatening many calcifying organisms, including corals. Here we assessed autotrophy vs heterotrophy shifts in the Mediterranean zooxanthellate scleractinian coral Balanophyllia europaea acclimatized to low pH/high pCO2 conditions at a CO2 vent off Panarea Island (Italy). Dinoflagellate endosymbiont densities were higher at lowest pH Sites where changes in the distribution of distinct haplotypes of a host-specific symbiont species, Philozoon balanophyllum, were observed. An increase in symbiont C/N ratios was observed at low pH, likely as a result of increased C fixation by higher symbiont cell densities. δ13C values of the symbionts and host tissue reached similar values at the lowest pH Site, suggesting an increased influence of autotrophy with increasing acidification. Host tissue δ15N values of 0‰ strongly suggest that diazotroph N2 fixation is occurring within the coral tissue/mucus at the low pH Sites, likely explaining the decrease in host tissue C/N ratios with acidification. Overall, our findings show an acclimatization of this coral-dinoflagellate mutualism through trophic adjustment and symbiont haplotype differences with increasing acidification, highlighting that some corals are capable of acclimatizing to ocean acidification predicted under end-of-century scenarios.

Multidimensional assessment of time perception along the continuum of Alzheimer's Disease and evidence of alterations in subjective cognitive decline.

Timing alterations occur in Alzheimer's disease (AD), even in early stages (mild cognitive impairment, MCI). Moreover, a stage named subjective cognitive decline (SCD), in which individuals perceive a change in cognitive performance not revealed by neuropsychological tests, has been identified as a preclinical phase of AD. However, no study to date has investigated different dimensions of time processing along the continuum from physiological to pathological aging, and whether timing alterations occur in SCD. Here a sample of participants with SCD, MCI, AD and healthy controls (HC) performed tasks assessing prospective duration estimation, production, reproduction, implicit temporal learning in conditions dependent from external cues (externally-cued learning, ECL) or independent from external cues (internally-based learning, IBL), retrospective duration estimation, the subjective experience of time and the temporal collocation of events. AD patients performed worse than HC and SCD in prospective timing, and in collocating events in time. The subjective experience of time did not differ between groups. Concerning temporal learning, AD performed worse in ECL than in IBL, whereas SCD performed worse in IBL than in ECL. SCD, MCI and AD patients all showed errors greater than HC in retrospective duration estimation. Results point to implicit temporal learning in externally-cued conditions and retrospective time estimation as possible early markers of cognitive decline.

Fecal bacteria contamination in the Adriatic Sea: Investigating environmental factors and modeling to manage recreational coastal waters.

This study is based on assessing fecal indicator bacteria contamination along meteorological, hydrological and physical-chemical variables after high rainy events during the summer period. The study focused on four different coastal sites in the western and eastern Adriatic coast characterized by various geomorphological and hydrological features, levels of urbanization and anthropogenic pressures, with the aim of finding appropriate and effective solutions to ensure the safety and sustainability of tourism and public health. Detailed in-situ survey revealed a wide range of fecal indicator bacterial (FIB) across the different river mouths with concentrations of E. coli ranging from 165 to 6700 CFU 100 mL-1. It was found that nitrogen compounds track microbial load and acted as tracers for fecal contaminants. Further, a modelling tool was also used to analyze the spatial and temporal distribution of fecal pollution at these coastal sites. The integrated monitoring through high frequent survey in river waters and modeling framework allowed for the estimation of fecal indicator bacterial load at the river mouth and examination of fecal pollutant dispersion in recreational waters, considering different scenarios of fecal dispersion along the coast. This study formed the basis of a robust decision support system aimed at improving the management of recreational areas and ensuring the protection of water bodies through efficient management of bathing areas.

Cortical complexity alterations in the medial temporal lobe are associated with Alzheimer's disease psychosis.

Psychosis is frequent in Alzheimer's disease (AD) and it is associated with a worse disease course. AD psychosis may represent a distinct AD phenotype, though its specific neurobiological underpinnings have yet to be identified. This study investigated neural underpinnings of AD psychosis using surface-based-morphometry.Data from 32 AD patients, 17 with psychosis (AD-P) and 15 without were analyzed. Average cortical complexity (fractal dimension, FD) was estimated for each theoretically motivated ROI and patient. First, we compared regional FD in AD-P and AD patients. Then we calculated the correlation coefficients between FD and the severity of misidentification and paranoid psychotic symptoms. AD-P showed decreased FD in ventral-visual-stream compared to AD, suggesting that perceptual processes might be pivotal in psychosis. A negative correlation was found between misidentification severity and FD in the entorhinal cortex suggesting that misidentification may be specifically associated with alterations in regions involved in high-level perceptual and contextualization processes.

Prevalence and Safety of COVID-19 Vaccination in Community-Dwelling People with Dementia: Findings from a Tertiary Memory Clinic in Italy.

This study aimed to explore the prevalence and safety of SARS-CoV-2 vaccination in individuals with dementia. Patients with mild cognitive impairment or dementia were recruited at a tertiary memory clinic, from March 15 to September 15, 2021. Information on COVID-19 vaccination and adverse events experienced after vaccine administration were collected from caregivers. Two-hundred-seventy subjects were finally recruited. Among them, 253 (93.7%) had received the vaccine and only 69 (27.3%) experienced adverse events. Cognitive and behavioral changes following immunization were only rarely reported. COVID-19 vaccination is safe and well-tolerated in patients with cognitive impairment who should be prioritized in the vaccination campaign.

Occurrence and distribution of microbial pollutants in coastal areas of the Adriatic Sea influenced by river discharge.

The transport of a variety of pollutants from agricultural, industrial and urbanised areas makes rivers major contributors to the contamination of coastal marine environments. Too little is known of their role in carrying pathogens to the coast. We used DNA-based metabarcoding data to describe the microbial community composition in seawater and sediment collected in front of the estuary of the Tronto, the Chienti and the Esino, three Italian rivers with different pollution levels that empty into the north-central Adriatic Sea, and to detect and measure within these communities the relative abundance of microbial pollutants, including traditional faecal indicators and alternative faecal and sewage-associated pollutants. We then applied the FORENSIC algorithm to distinguish human from non-human sources of microbial pollution and FAPROTAX to map prokaryotic clades to established metabolic or other ecologically relevant functions. Finally, we searched the dataset for other common pathogenic taxa. Seawater and sediment contained numerous potentially pathogenic bacteria, mainly faecal and sewage-associated. The samples collected in front of the Tronto estuary showed the highest level of contamination, likely sewage-associated. The pathogenic signature showed a weak but positive correlation with some nutrients and strong correlations with some polycyclic aromatic hydrocarbons. This study confirms that rivers transport pathogenic bacteria to the coastal sea and highlights the value of expanding the use of HTS data, source tracking and functional identification tools to detect microbial pollutants and identify their sources with a view to gaining a better understanding of the pathways of sewage-associated discharges to the sea.

The Applications of 3D Imaging and Indocyanine Green Dye Fluorescence in Laparoscopic Liver Surgery.

Laparoscopic liver resections have gained widespread popularity among hepatobiliary surgeons and is nowadays performed for both standard and more complex hepatectomies. Given the increased technical challenges, preoperative planning and intraoperative guidance is pivotal in laparoscopic surgery to safely carry out complex and oncologically safe hepatectomies. Modern tools can help both preoperatively and intraoperatively and allow surgeons to perform more precise hepatectomies. Preoperative 3D reconstructions and printing as well as augmented reality can increase the knowledge of the specific anatomy of the case and therefore plan the surgery accordingly and tailor the procedure on the patient. Furthermore, the indocyanine green retention dye is an increasingly used tool that can nowadays improve the precision during laparoscopic hepatectomies, especially when considering anatomical resection. The use of preoperative modern imaging and intraoperative indocyanine green dye are key to successfully perform complex hepatectomies such as laparoscopic parenchymal sparing liver resections. In this narrative review, we discuss the aspects of preoperative and intraoperative tools that are nowadays increasingly used in experienced hepatobiliary centers.

Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity.

Brain organoids are in vitro three-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10-20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly standardized, reproducible, and fast (5 weeks) murine brain organoid model starting from embryonic neural stem cells. We obtained brain organoids, which progressively differentiated and self-organized into 3D networks of functional neurons with dorsal forebrain phenotype. Furthermore, by adding the morphogen WNT3a, we generated brain organoids with specific hippocampal region identity. Overall, our results showed the establishment of a fast, robust and reproducible murine 3D in vitro brain model that may represent a useful tool for high-throughput drug screening and disease modeling.

[Role of anastomotic configuration in ileocolic resection for Crohn's disease]. / Ruolo della configurazione anastomotica nella resezione ileocolica per malattia di Crohn.

Crohn's disease is characterised by a high incidence of perianastomotic recurrence after ileocolic resection. The influence of the anastomotic configuration on the incidence of reoperation was evaluated in patients undergoing resection for Crohn's disease. In our Institution, from 1993 to 2007, 308 consecutive patients affected by ileocolic Crohn's disease were submitted to 343 ileocolic resections or right colectomies. In 292 cases (85.1%), an antiperistaltic side-to-side (or functional end-to-end) anastomosis was performed, with an 80 mm linear stapler in 190 cases, a 100 mm linear stapler in 79, and a hand-sewn anastomosis in 23. The other hand-sewn anastomotic configurations were: 30 (8.8%) side-to-side isoperistaltic, 15 (4.3%) end-to-side and 6 (1.8%) end-to-end. The overall morbidity was 7.3%, with two postoperative deaths (0.6%) with no significant differences between groups. There were 38 overall recurrences (11%). In the side-to-side antiperistaltic group, the rate of recurrence was 8.2%, significantly lower than the recurrence rates observed in the other anastomoses (26.9%, p = 0.002), especially side-to-side isoperistaltic anastomosis (33.3%, p = 0.001). Early recurrences (< 1-year) were 2.6%, without significant differences between groups. There was a higher trend for end-to-end anastomosis (16.6%). In the side-to-side antiperistaltic group the morbidity was higher in the large mechanical anastomoses (100 mm length), but the recurrence rate was lower in this group as compared to the 80 mm anastomoses (1.2% vs. 12.1%, p = 0.006). Our non-randomised study suggests a better trend for the wide side-to-side antiperistaltic technique in terms of recurrence rate. These observations need further investigation with randomised controlled trials to compare the different anastomotic procedures.

Somatosensory Temporal Discrimination Threshold in Patients with Cognitive Disorders.

BACKGROUND: The temporal processing of sensory information can be evaluated by testing the somatosensory temporal discrimination threshold (STDT), which is defined as the shortest interstimulus interval needed to recognize two sequential sensory stimuli as separate in time. The STDT requires the functional integrity of the basal ganglia and of the somatosensory cortex (S1). Although there is evidence that time processing is impaired in patients with Alzheimer's disease (AD), no study has yet investigated STDT in patients with various degree of cognitive impairment. OBJECTIVE: The aim of our study was to understand how cognition and attention deficits affect STDT values in patients with cognitive abnormalities. METHODS: We enrolled 63 patients: 28 had mild-moderate AD, 16 had mild cognitive impairment (MCI), and the remaining 19 had subjective cognitive deficit (SCD). A group of 45 age-matched healthy subjects acted as controls. Paired tactile stimuli for STDT testing consisted of square-wave electrical pulses delivered with a constant current stimulator through surface electrodes over the distal phalanx of the index finger. RESULTS: STDT values were higher in AD and MCI patients than in SCD subjects or healthy controls. Changes in the STDT in AD and MCI were similar in both conditions and did not correlate with disease severity. CONCLUSIONS: STDT alterations in AD and MCI may reflect a dysfunction of the dopaminergic system, which signals salient events and includes the striatum and the mesocortical and mesolimbic circuits.