Land/Water Aerobic Activities: Two Sides of the Same Coin. A Comparative Analysis on the Effects in Cognition of Alzheimer's Disease.

 Evidence in the literature indicates that aerobic physical activity may have a protective role in aging pathologies. However, it has not been clarified whether different types of aerobic exercise produce different effects. In particular, these potential differences have not been explored in patients with Alzheimer's disease (AD). The present narrative review has the specific aim of evaluating whether land (walking/running) and water (swimming) aerobic activities exert different effects on cognitive functions and neural correlates in AD patients. In particular, the investigation is carried out by comparing the evidence provided from studies on AD animal models and on patients. On the whole, we ascertained that both human and animal studies documented beneficial effects of land and water aerobic exercise on cognition in AD. Also, the modulation of numerous biological processes is documented in association with structural modifications. Remarkably, we found that aerobic activity appears to improve cognition per se, independently from the specific kind of exercise performed. Aerobic exercise promotes brain functioning through the secretion of molecular factors from skeletal muscles and liver. These molecular factors stimulate neuroplasticity, reduce neuroinflammation, and inhibit neurodegenerative processes leading to amyloid-ß accumulation. Additionally, aerobic exercise improves mitochondrial activity, reducing oxidative stress and enhancing ATP production. Aerobic activities protect against AD, but implementing exercise protocols for patients is challenging. We suggest that health policies and specialized institutions should direct increasing attention on aerobic activity as lifestyle modifiable factor for successful aging and age-related conditions.

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy.

Endometrial cancer (EC) is the most prevalent gynecological cancer in high-income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity-related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR-199a-5p, miR-449a, miR-449b-5p) in normal-weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity-related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity-related pathways and that may provide novel implications for the clinical management of obese EC patients.

Bariatric Surgery and COVID-19: a Change of Perspective in a New Phase of the Pandemic.

PURPOSE: The protective role of bariatric surgery (BS) against COVID-19 has been reported by several studies, showing, in the first pandemic waves, better outcome of the infection in patients that had undergone BS. With the virus progressive endemicity, BS benefits on COVID-19 clinical course could appear less evident, while COVID-19 effects on BS outcomes must be investigated. In this national multicentric cross-sectional study, we compared COVID-19 incidence and clinical course between a cohort of patients that had undergone BS (OP) and a cohort of candidates to BS (WS); moreover, we analyzed BS outcomes based on SARS-CoV-2 positivity/negativity. METHODS: From June to December 2021, 522 patients from five Italian referral centers were administered an 87-item telephonic questionnaire completing the analysis of electronic medical records. Demographics, COVID-19 "tested" incidence, suggestive symptoms and clinical outcome parameters of OP and WS were compared. BS outcomes parameters were compared between OP that developed the disease or not. RESULTS: COVID-19 incidence was the same in OP and WS, while symptoms and clinical course seemed milder in OP, with no data individually reaching statistical significance. OP who developed SARS-CoV-2 infection had higher excess weight loss than negative OP (66.8% ± 22.1 vs. 57.7% ± 22.8, p = 0.029). Positive OP had had gastric-bypass (RYGB/OAGB) more frequently than negative ones (38.4% vs. 18.2%, p = 0.025). CONCLUSION: With the disease becoming endemic, BS protective role against COVID-19 seems clinically less relevant. BS outcomes can be affected by COVID-19, thus imposing careful follow-up for positive patients, especially if undergoing gastric-bypass.

Synaptic and transcriptomic features of cortical and amygdala pyramidal neurons predict inefficient fear extinction.

Fear-related disorders arise from inefficient fear extinction and have immeasurable social and economic costs. Here, we characterize mouse phenotypes that spontaneously show fear-independent behavioral traits predicting adaptive or maladaptive fear extinction. We find that, already before fear conditioning, specific morphological, electrophysiological, and transcriptomic patterns of cortical and amygdala pyramidal neurons predispose to fear-related disorders. Finally, by using an optogenetic approach, we show the possibility to rescue inefficient fear extinction by activating infralimbic pyramidal neurons and to impair fear extinction by activating prelimbic pyramidal neurons.

Environmental Enrichment Protects against Neurotoxic Effects of Lipopolysaccharide: A Comprehensive Overview.

Neuroinflammation is a pathophysiological condition associated with damage to the nervous system. Maternal immune activation and early immune activation have adverse effects on the development of the nervous system and cognitive functions. Neuroinflammation during adulthood leads to neurodegenerative diseases. Lipopolysaccharide (LPS) is used in preclinical research to mimic neurotoxic effects leading to systemic inflammation. Environmental enrichment (EE) has been reported to cause a wide range of beneficial changes in the brain. Based on the above, the purpose of the present review is to describe the effects of exposure to EE paradigms in counteracting LPS-induced neuroinflammation throughout the lifespan. Up to October 2022, a methodical search of studies in the literature, using the PubMed and Scopus databases, was performed, focusing on exposure to LPS, as an inflammatory mediator, and to EE paradigms in preclinical murine models. On the basis of the inclusion criteria, 22 articles were considered and analyzed in the present review. EE exerts sex- and age-dependent neuroprotective and therapeutic effects in animals exposed to the neurotoxic action of LPS. EE's beneficial effects are present throughout the various ages of life. A healthy lifestyle and stimulating environments are essential to counteract the damages induced by neurotoxic exposure to LPS.

Dietary Protection against Cognitive Impairment, Neuroinflammation and Oxidative Stress in Alzheimer's Disease Animal Models of Lipopolysaccharide-Induced Inflammation.

Alzheimer's disease (AD) is a rapidly growing epidemic with a heavy social and economic burden. Evidence suggests that systemic inflammation, dysregulation of the immune response and the resulting neuroinflammation and neurodegeneration play a significant role in AD pathogenesis. Currently, given that there is no fully convincing cure for AD, the interest in lifestyle factors (such as diet), which potentially delay onset and reduce the severity of symptoms, is increasing. This review is aimed at summarizing the effects of dietary supplementation on cognitive decline, neuroinflammation and oxidative stress in AD-like animal models with a focus on neuroinflammation induced by lipopolysaccharide (LPS) injection, which mimics systemic inflammation in animals. The compounds reviewed include curcumin, krill oil, chicoric acid, plasmalogens, lycopene, tryptophan-related dipeptides, hesperetin and selenium peptides. Despite the heterogeneity of these compounds, there is a strong consensus on their counteracting action on LPS-induced cognitive deficits and neuroinflammatory responses in rodents by modulating cell-signaling processes, such as the NF-κB pathway. Overall, dietary interventions could represent an important resource to oppose AD due to their influence in neuroprotection and immune regulation.

Walking, Running, Swimming: An Analysis of the Effects of Land and Water Aerobic Exercises on Cognitive Functions and Neural Substrates.

In the brain and cognitive reserves framework, aerobic exercise is considered as a protective lifestyle factor able to induce positive effects on both brain structure and function. However, specific aspects of such a beneficial effect still need to be completely clarified. To this aim, the present narrative review focused on the potential brain/cognitive/neural reserve-construction mechanisms triggered by different aerobic exercise types (land activities; such as walking or running; vs. water activities; such as swimming), by considering human and animal studies on healthy subjects over the entire lifespan. The literature search was conducted in PubMed database. The studies analyzed here indicated that all the considered kinds of activities exert a beneficial effect on cognitive/behavioral functions and on the underlying brain neurobiological processes. In particular, the main effects observed involve the cognitive domains of memory and executive functions. These effects appear related to structural and functional changes mainly involving the fronto-hippocampal axis. The present review supports the requirement of further studies that investigate more specifically and systematically the effects of each type of aerobic activity, as a basis to plan more effective and personalized interventions on individuals as well as prevention and healthy promotion policies for the general population.

Transcriptomic and Network Analyses Reveal Immune Modulation by Endocannabinoids in Approach/Avoidance Traits.

Approach and avoidance (A/A) tendencies are stable behavioral traits in responding to rewarding and fearful stimuli. They represent the superordinate division of emotion, and individual differences in such traits are associated with disease susceptibility. The neural circuitry underlying A/A traits is retained to be the cortico-limbic pathway including the amygdala, the central hub for the emotional processing. Furthermore, A/A-specific individual differences are associated with the activity of the endocannabinoid system (ECS) and especially of CB1 receptors whose density and functionality in amygdala differ according to A/A traits. ECS markedly interacts with the immune system (IS). However, how the interplay between ECS and IS is associated with A/A individual differences is still ill-defined. To fill this gap, here we analyzed the interaction between the gene expression of ECS and immune system (IS) in relation to individual differences. To unveil the deep architecture of ECS-IS interaction, we performed cell-specific transcriptomics analysis. Differential gene expression profiling, functional enrichment, and protein-protein interaction network analyses were performed in amygdala pyramidal neurons of mice showing different A/A behavioral tendencies. Several altered pro-inflammatory pathways were identified as associated with individual differences in A/A traits, indicating the chronic activation of the adaptive immune response sustained by the interplay between endocannabinoids and the IS. Furthermore, results showed that the interaction between the two systems modulates synaptic plasticity and neuronal metabolism in individual difference-specific manner. Deepening our knowledge about ECS/IS interaction may provide useful targets for treatment and prevention of psychopathology associated with A/A traits.

A Retrospective Study on Statins and Post-stroke Patients: What About Functional Outcome and Follow-Up in a Stroke Rehabilitation Cohort?

Objective: Statins exert pleiotropic effects by influencing several mechanisms, including synaptogenesis, neurogenesis, cerebral flow regulation, and angiogenesis. Results from in vitro and animal models suggest that statins could have beneficial effect on functional recovery and outcome after stroke events. However, results in human studies are still controversial. The aim of our study was to evaluate the role of statin in influencing functional outcome and subsequent clinical follow-up in a large cohort of post-stroke rehabilitation patients. Methods: This retrospective study consecutively enrolled 413 adult patients with stroke event, admitted to the division of Neurorehabilitation of the IRCCS ICS Maugeri, Veruno (Italy), for an individual rehabilitation program between 2015 and 2017. Follow-up lasted 3-5 years after discharge. Demographic data, etiology, classification, and anatomical site of stroke lesion, functional assessment, use and duration of statin therapy, and death during hospitalization were collected at baseline and on discharge. Clinical data on subsequent follow-up were also evaluated, considering these as variables: stroke recurrence, bone fractures, cardiovascular complications, and death. Results: In our cohort, 177 patients (42.9%) were prescribed statin therapy, of whom 50 (28.2%) before the stroke event and 127 (71.8%) at the beginning of the rehabilitation process. The use and type of statin therapy as well as the duration of treatment were not associated with recovery and functional outcome, regardless of confounders including sex, age, etiology, and site of stroke lesion, and initial functional level. For what concern post-discharge clinical follow-up, the use of statin therapy was significantly associated with a lower risk of bone fractures (OR = 0.095, CI 95%: 0.012-0.743, p = 0.01) independently from age, sex, initial and final functional level, and comorbidities. Conclusions: The use of statins does not seem to influence the functional outcome in post-stroke patients. However, they could exert a protective role against bone fractures during post-discharge follow-up, suggesting further evaluation on this topic.

Effectiveness of Telerehabilitation on Motor Impairments, Non-motor Symptoms and Compliance in Patients With Parkinson's Disease: A Systematic Review.

Introduction: Parkinson's disease (PD) is a chronic neurodegenerative disease involving a progressive alteration of the motor and non-motor function. PD influences the patient's daily living and reduces participation and quality of life in all phases of the disease. Early physical exercise can mitigate the effects of symptoms but access to specialist care is difficult. With current technological progress, telemedicine, and telerehabilitation is now a viable option for managing patients, although few studies have investigated the use of telerehabilitation in PD. In this systematic review, was investigated whether telerehabilitation leads to improvements in global or specific motor tasks (gait and balance, hand function) and non-motor dysfunction (motor speech disorder, dysphagia). The impact of TR on quality of life and patient satisfaction, were also assessed. The usage of telerehabilitation technologies in the management of cognitive impairment was not addressed. Method: An electronic database search was performed using the following databases: PubMed/MEDLINE, COCHRANE Library, PEDro, and SCOPUS for data published between January 2005 and December 2019 on the effects of telerehabilitation systems in managing motor and non-motor symptoms. This systematic review was conducted in accordance with the PRISMA guideline and was registered in the PROSPERO database (CRD42020141300). Results: A total of 15 articles involving 421 patients affected by PD were analyzed. The articles were divided into two categories based on their topic of interest or outcome. The first category consisted of the effects of telerehabilitation on gait and balance (3), dexterity of the upper limbs (3), and bradykinesia (0); the second category regarded non-motor symptoms such as speech disorders (8) and dysphagia (0). Quality of life (7) and patient satisfaction (8) following telerehabilitation programs were also analyzed, as well as feasibility and costs. Conclusion: Telerehabilitation is feasible in people affected by PD. Our analysis of the available data highlighted that telerehabilitation systems are effective in maintaining and/or improving some clinical and non-clinical aspects of PD (balance and gait, speech and voice, quality of life, patient satisfaction). Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42020141300.

Optogenetic Stimulation of Prelimbic Pyramidal Neurons Maintains Fear Memories and Modulates Amygdala Pyramidal Neuron Transcriptome.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons and amygdala gene expression to analyze the specific transcriptional pathways associated to adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over photo-activable PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and associated to strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological, and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Influence of systemic infection and comorbidities on rehabilitation outcomes in severe acquired brain injury.

BACKGROUND: Severe infectious complications are a frequent problem in patients with disability due to a severe acquired brain injury. Previous studies reported that the rehabilitation outcome is significantly lower in patients colonized or infected. However, these results could be influenced by comorbidities of those patients admitted in rehabilitation hospital with a lower functional status. AIM: To explore the influence of systemic infection, in particular concerning multidrug resistant bacteria and analyze the role of comorbidities, as a risk factor for the development of systemic infection, on rehabilitation outcomes in patients with severe brain injury. DESIGN: This research is a cohort, prospective-observational study, comparing patients with and without systemic infections, in terms of rehabilitation outcomes. SETTING: An Italian Intensive Care Rehabilitation Department. POPULATION: A group of 221 patients (mean age: 59 years, range: 16-93 years, 127 males, 94 females) with severe acquired brain injury admitted to rehabilitation hospital. METHODS: We compared the rehabilitation outcomes between patients with and without a systemic infection (at least a positive blood culture) during the rehabilitation period. A secondary analysis was performed on 70 patients with infection versus 70 patients without infection, matched for functional status at admission. The used clinical scores were: Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Coma Recovery Scale Revised (CRS-R), Glasgow Coma Scale (GCS), Functional Independence Measure (FIM), Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), Levels of Cognitive Functioning (LCF) administered at admission and discharge. Length of hospitalization and the role of comorbidities were also considered. RESULTS: The group of patients with systemic infection (in particular due to Gram-negative bacteria) had a significantly lower outcome for 5 out 6 clinical scales and with a more than doubled length of hospitalization (P<0.001). However, these patients with, at least, a positive blood culture resulted having lower functional status at admission. In the secondary analysis, worst outcome was found in patients with positive blood culture in terms of FIM (P=0.033), GOS (P=0.048), and CRS-R (P=0.001). CONCLUSIONS: Systemic infections during rehabilitation increased the length of hospitalization and reduce the rehabilitative outcomes, even when the analysis was performed on groups matched for the functional status at admission. Moreover, the cardiological and endocrine metabolic comorbidities seem to influence the outcome, without representing a further risk factor for systemic infection. CLINICAL REHABILITATION IMPACT: The impact of infections during rehabilitation inpatient should be more taken into account, with specific procedures and suitable environments to avoid the diffusions of infections.

How important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised COVID-19 patients? Results from a single Italian centre.

OBJECTIVE: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. RESEARCH DESIGN AND METHODS: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. RESULTS: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31-4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53-9.74, P < 0.001). A significantly higher risk of death was observed in patients with a BMI ≥ 35 kg/m2 (OR: 12.1; 95% CI: 3.25-45.1, P < 0.001). CONCLUSIONS: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.

Endoscopic Ultrasound-Guided Stented Gastro-Gastrostomy for Strictured Vertical Banded Gastroplasty.

Herein, we make a video presentation of an endoscopic reversal of a strictured vertical banded gastroplasty (VBG), carried out through an endoscopic ultrasonography (EUS)-guided transluminal therapy system, in order to accurately identify the common gastric wall and to allow the application of an endoscopic stent. The operative time was 60 min, and no intraoperative complication was recorded. On postoperative day 1, an upper GI swallow showed the oral contrast easily flowing into the body of the stomach throughout the stent. A semi-solid diet was started on day 1. The postoperative course was uneventful, and the patient was discharged on day 2. At the 3-month follow-up visit, the patient denied further symptoms. The follow-up upper GI swallow and endoscopy showed a patent gastro-gastrostomy and no residual gastric pouch dilation or stagnation of the oral contrast, and the stent was therefore removed. Gastro-gastrostomy by endoscopic stenting appears to be an effective option to relief symptoms in strictured VBG, and EUS guidance has made access to the target structure easier and safer.

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study.

To promote efficient explorative behaviors, subjects adaptively select spatial navigational strategies based on landmarks or a cognitive map. The hippocampus works alone or in conjunction with the dorsal striatum, both representing the neuronal underpinnings of the navigational strategies organized on the basis of different systems of spatial coordinate integration. The high expression of cannabinoid type 1 (CB1) receptors in structures related to spatial learning-such as the hippocampus, dorsal striatum and amygdala-renders the endocannabinoid system a critical target to study the balance between landmark- and cognitive map-based navigational strategies. In the present study, mice treated with the CB1-inverse agonist/antagonist AM251 or vehicle were trained on a Circular Hole Board, a task that could be solved through either navigational strategy. At the end of the behavioral testing, c-Fos immunoreactivity was evaluated in specific nuclei of the hippocampus, dorsal striatum and amygdala. AM251 treatment impaired spatial learning and modified the pattern of the performed navigational strategies as well as the c-Fos immunoreactivity in the hippocampus, dorsal striatum and amygdala. The present findings shed light on the involvement of CB1 receptors as part of the selection system of the navigational strategies implemented to efficiently solve the spatial problem.

Role of 2 common variants of 5HT2A gene in medication overuse headache.

OBJECTIVE: The aim of the present study was to evaluate a possible involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption. BACKGROUND: Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month. METHODS: Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Genotype-specific risks were estimated as odds ratios with associated 95% confidence intervals by unconditional logistic regression and adjusted for age and gender. A stepwise multiple linear regression analysis was employed to identify significant predictors of the number of drug doses taken per month. RESULTS: No significant association was found between 5HT2A A and 1438G and C516T gene polymorphisms and MOH risk. In contrast, a higher consumption of monthly drug doses was observed among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients (median 30, range 12-128) (Mann-Whitney U-test, P = .018). In the stepwise multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of overused drug (P = .047) emerged as significant, independent predictors of the monthly drug consumption in MOH patients. CONCLUSIONS: Although our results do not support a major role of the A-1438G and C516T polymorphic variants of the 5HT2A gene in the susceptibility of MOH, our findings support an influence of the C516T polymorphism on the number of symptomatic drug doses taken and, possibly, on the drug-seeking behavior in these patients.