Erythropoietin as a Neuroprotective Drug for Newborn Infants: Ten Years after the First Use

Protective strategies against perinatal brain injury represent a major challenge for modern neonatology. Erythropoietin (Epo) enhances endogenous mechanisms of repair and angiogenesis. In order to analyse the newest evidence on the role of Epo in prematurity, hypoxic ischemic encephalopathy (HIE) and perinatal stroke, a critical review using 2020 PRISMA statement guidelines was conducted. This review uncovered 26 clinical trials examining the use of Epo for prematurity and brain injury-related outcomes. The effects of Epo on prematurity were analysed in 16 clinical trials. Erythropoietin was provided until 32-35 weeks of corrected postnatal age with a dosage between 500-3000 UI/kg/dose. Eight trials reported the Epo effects on HIE term newborn infants: Erythropoietin was administered in the first weeks of life, at different multiple doses between 250-2500 UI/kg/dose, as either an adjuvant therapy with hypothermia or a substitute for hypothermia. Two trials investigated Epo effects in perinatal stroke. Erythropoietin was administered at a dose of 1000 IU/kg for three days. No beneficial effect in improving morbidity was observed after Epo administration in perinatal stroke. A positive effect on neurodevelopmental outcome seems to occur when Epo is used as an adjuvant therapy with hypothermia in the HIE newborns. Administration of Epo in preterm infants still presents inconsistencies with regard to neurodevelopmental outcome. Clinical trials show significant differences mainly in target population and intervention scheme. The identification of specific markers and their temporal expression at different time of recovery after hypoxia-ischemia in neonates might be implemented to optimize the therapeutic scheme after hypoxic-ischemic injury in the developing brain. Additional studies on tailored regimes, accounting for the risk stratification of brain damage in newborns, are required

Caregiver burden on sexual intimacy and marital satisfaction

SUMMARY Objective: This study investigates affective and sexual dimensions in partners involved as caregivers of Alzheimer dementia (AD) subjects. A negative correlation between burden of the caregiver and sexual-affective quality of life was assumed. Design and methods: Hundred participants with AD partner (33 male, 67 female), aged between 55 and 85 years were recruited and data were collected from the Caregiver Burden Inventory scale and a semi-structured interview that included demographic information, medical history, relationship and sexual satisfaction, and current sexual function. AD group was compared with a control group (CG) (N ¼ 100) matched for age, sex, education and marital status on measures of the semi-structured interview. Data were analysed using frequency count, univariate analysis (chi-squared and ANOVA) and bivariate correlation. Results: The findings revealed that mean burden level was 31.59 (SD 19.51). A difference between experimental and CGs was found for sexual and affective marital satisfaction (p < 0.05). The same variables showed a rather negative correlation with total burden levels (r ¼ )0.374, p < 0.001; r ¼ )0.448, p < 0.001). What's known Alzheimer dementia and the global impairment of intellectual function, as well as its physiological correlates, have strong influence on the quality of life with the consequent need of assistance which could determine a high burden level in the caregiver. The attendant cognitive changes that occur in the Alzheimer patient present many, often conflicting, challenges to a couple's sexual functioning 2,

Palmitoylethanolamide modulates high-fat diet-shaped gut function and microbiota composition in obese mice

Introduction/Background & aims: Emerging data indicate a pivotal role for gut microbiota in the progression of obesity. Indeed, in the gut, high-fat diet (HFD) intake induces the loss of barrier integrity, causing the transfer of detrimental factors (i.e. lipopolysaccharide, LPS) into the systemic circulation, leading to metabolic dysfunctions and an overall state of low-grade inflammation, called “met- ainflammation” [1]. The metabolic and anti-inflammatory activities of palmitoylethanolamide (PEA), an endogenous lipid mediator, prompt us to evaluate its capability to improve intestinal homeostasis and shape gut microbiota composition altered in HFD-fed obese mice. Method/Summary of work: Male C57Bl/6 J mice received standard diet (STD) or HFD (n = 10 each group). After 12 weeks, a subgroup of HFD mice was treated with PEA (30 μg/kg/die per os) for 7 weeks. Body weight was monitored during the treatment and fat mass was evaluated at the end of experimental time. Systemic parameters and intestinal function were examined using ELISA assay, and Real-Time PCR analysis, respectively. Faecal microbiota was studied by per- forming 16S rDNA amplicon sequencing and linear discriminant analy- sis in order to obtain the operational taxonomic units (OTUs) defining the bacterial communities

Sudden Infant Death Syndrome: Beyond Risk Factors

Sudden infant death syndrome (SIDS) is defined as "the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review". A significant decrease of SIDS deaths occurred in the last decades in most countries after the beginning of national campaigns, mainly as a consequence of the implementation of risk reduction action mostly concentrating on the improvement of sleep conditions. Nevertheless, infant mortality from SIDS still remains unacceptably high. There is an urgent need to get insight into previously unexplored aspects of the brain system with a special focus on high-risk groups. SIDS pathogenesis is associated with a multifactorial condition that comprehends genetic, environmental and sociocultural factors. Effective prevention of SIDS requires multiple interventions from different fields. Developing brain susceptibility, intrinsic vulnerability and early identification of infants with high risk of SIDS represents a challenge. Progress in SIDS research appears to be fundamental to the ultimate aim of eradicating SIDS deaths. A complex model that combines different risk factor data from biomarkers and omic analysis may represent a tool to identify a SIDS risk profile in newborn settings. If high risk is detected, the infant may be referred for further investigations and follow ups. This review aims to illustrate the most recent discoveries from different fields, analyzing the neuroanatomical, genetic, metabolic, proteomic, environmental and sociocultural aspects related to SIDS

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

IntroductionThe involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.MethodsWe performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.ResultsThe results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.ConclusionsThese data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases

L’insediamento a bifacciali di Guado San Nicola (Monteroduni, Molise, Italia)

La monografia rappresenta un compendio di lavori specialistici sul sito paleolitico di Guado San Nicola a Monteroduni (Molise, Italia), oggetto di ricerche sistematiche ed indagini interdisciplinari inaugurate nell’area a partire dal 2000 dall'Università degli Studi di Ferrara. Il sito, ascrivibile al MIS 10/11, costituisce un tassello importante nell’ambito della ricostruzione del quadro del popolamento umano della penisola italiana e dell’intero bacino del Mediterraneo, alla luce delle considerazioni crono-stratigrafiche, della ricchezza della documentazione e della presenza di elementi innovativi dal punto di vista culturale quali la padronanza del metodo Levallois e l’uso di percussori in palchi di cervo

N-(1-carbamoyl-2-phenylethyl) butyramide reduces antibioticinduced intestinal injury, innate immune activation and modulates microbiota composition

The use/misuse of antibiotics leads to pathological features referring to antibiotic-induced intestinal injury (AIJ), a clinical issue that plays a prominent role in the development of severe digestive disturbances. AIJ is characterized by loss of intestinal architecture and function, dysbiosis and bacterial translocation into the liver, triggering hepatic inflammation. This study aimed at determining the beneficial effect of N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), a butyrate releasing compound, in ceftriaxone-induced intestinal injury. To this purpose, mice receiving ceftriaxone (8 g∙kg−1/die, per os) for five days, were treated with FBA (212,5 mg∙kg−1/die, per os) for five or fifteen days. FBA modulated key players of innate immunity in antibiotic-injured gut tissues, reducing inflammatory process and improving the anti-inflammatory and resolving pattern. FBA also improved colonic architecture and intestinal integrity. Interestingly, we also observed a remodeling of gut microbiota composition related to an increase of metabolic pathways related to lactate and butyrate production. At mechanistic level, FBA induced histone acetylation and increased the expression of GPR43 and monocarboxylate transporter 1 in colon. Our data clearly demonstrated that FBA has multiple converging mechanisms in limiting intestinal and hepatic alterations to counteract AIJ