Histological and biological developmental characterization of the human cerebellar cortex

The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.     

Postbiotic Supplementation for Children and Newborn’s Health

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.     

The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System

The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network.     

Correction to: Intramuscular clodronate in erosive osteoarthritis of the hand is effective on pain and reduces serum COMP: a randomized pilot trial–The ER.O.D.E. study (ERosive Osteoarthritis and Disodium-clodronate Evaluation)

Clinical Rheumatology - One of the author names on this article was incorrectly tagged during the article mark-up; Luca Dalle Carbonare’s name has now been correctly tagged, with first name...     

Probability of cure in elderly Hodgkin's disease patients

BACKGROUND: Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of trials designed for them, useful information can be obtained only by retrospective analyses. METHODS: We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity. RESULTS: In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns). CONCLUSIONS: Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.     

The middle range of the number line orients attention to the left side of visual space

Mental representation of numbers is believed to be spatial in nature, with small numbers occupying the left and large numbers the right side of a putative mental number line. Consistent with this, presentation of numbers from the low and high ends of the mental number line induces covert shifts of spatial attention to the left and right side of visual space, respectively. However, the effect of the presentation of the middle range (containing numbers below and above the midpoint) of the number line on visual perception has so far not been studied. Here we show in two experiments, using a line bisection task and a simple target detection task, that processing of middle-range numbers affects allocation of visuospatial attention in a similar way as processing of small numbers, with attention shifted to the left side of space. We suggest that this pattern of results arises due to “anchoring” heuristics that participants use in number processing.     

Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients

A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].     

Clodronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open randomized pilot study

We evaluated the efficacy of clodronate for treating active erosive osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7 days, followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days, followed by 200 mg daily for the next 11 months. In group A, 21/24 patients completed the trial and obtained significant pain reduction (p < 0.001), Dreiser’s score (p = 0.012), and number of tender joints (p = 0.011). Strength of right (p = 0.04) and left (p = 0.016) hands, physician’s global assessment (p ≤ 0.001), and patient’s global assessment (p = 0.021) improved. In group B, 8/14 patients completed 12 months of the study, which showed the inefficacy of hydroxychloroquine and its lack of acceptance by patients (worsening pain and patient’s global assessment). Therefore, enrolment was stopped. Differences between groups showed a pain decreasing trend for group A and a slightly increasing one for group B (p = 0.018). Physician and patient global assessments showed a strong increase in group A compared with group B (p < 0.001). Clodronate is effective in erosive osteoarthritis; hydroxychloroquine seems to be ineffective.     

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Journal of Neurology - Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Based on the database of the...