Intrauterine growth pattern and birthweight discordance in twin pregnancies: a retrospective study

Background: Twins, compared to singletons, have an increased risk of perinatal mortality and morbidity, due mainly to a higher prevalence of preterm birth and low birthweight. Intrauterine growth restriction (IUGR) is also common and can affect one or both fetuses. In some cases, however, one twin is much smaller than the other (growth discordance). Usually, high birthweight discordance is associated with increased perinatal morbidity. The aim of this study is to describe the epidemiological features of a population of twins at birth, with particular reference to the interpretation and clinical effects of birthweight discordance. Methods: We evaluated retrospectively the clinical features of 70 infants born from twin pregnancies and assessed birthweight discordance in 31 pregnancies where both twins were followed at our institution. Discordance was treated both as a continuous and a categorical variable, using a cutoff of 18%. Possible relationships between birthweight discordance and other variables, such as maternal age, gestational age, birthweight percentile, number of SGA newborns in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of malformations, neonatal morbidity and death, were analyzed. Results: In our cohort birthweight percentile decreased slightly with increasing gestational age. Birthweight discordance, on the contrary, increased slightly with the increase of gestational age. A high discordance is associated to the presence of one SGA twin, with the other AGA or LGA. In our population, all 6 pregnancies in which discordance exceeded 18% belonged to this category (one SGA twin). Ht discordance at birth is associated to the presence of neonatal anemia in a twin, but it is not significantly related to weight discordance. Finally, in our case history, weight discordance is not associated in any way with the prevalence of malformations, morbidity and mortality. Conclusions: Birthweight discordance is an important indicator of complications that act asymmetrically on the two fetuses, affecting intrauterine growth in one of them, and usually determining the birth of a SGA infant. Our case history shows a significant statistical association between pair discordance and IUGR in one of the twins, but we could not demonstrate any relationship between discordance and the prevalence of malformations, morbidity and mortality

Single Inhaler LABA/LAMA for COPD

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field

Gut microbiota modulates seizure susceptibility

A bulk of data suggest that the gut microbiota plays a role in a broad range of diseases, including those affecting the central nervous system. Recently, significant differences in the intestinal microbiota of patients with epilepsy, compared to healthy volunteers, have been reported in an observational study. However, an active role of the intestinal microbiota in the pathogenesis of epilepsy, through the so-called "gut-brain axis," has yet to be demonstrated. In this study, we evaluated the direct impact of microbiota transplanted from epileptic animals to healthy recipient animals, to clarify whether the microbiota from animals with epilepsy can affect the excitability of the recipients' brain by lowering seizure thresholds. Our results provide the first evidence that mice who received microbiota from epileptic animals are more prone to develop status epilepticus, compared to recipients of "healthy" microbiota, after a subclinical dose of pilocarpine, indicating a higher susceptibility to seizures. The lower thresholds for seizure activity found in this study support the hypothesis that the microbiota, through the gut-brain axis, is able to affect neuronal excitability in the brain

The Association Between Intolerance of Uncertainty, Emotion Dysregulation, and Anxiety in Italian Non-Clinical Pre-Adolescents and Adolescents

Background: Anxiety symptoms are rather frequent in adolescence and associated with long-term negative consequences. Therefore, expanding knowledge on the factors that may underlie anxiety symptomatology is extremely relevant; to this end, intolerance of uncertainty and emotion dysregulation are of key interest. This study aimed to deepen the relation between intolerance of uncertainty and emotion regulation difficulties and to explore the role of these constructs in explaining anxiety levels in adolescence. Methods: Three hundred and fifty Italian non-clinical pre-adolescents and adolescents (age range: 11-17, 53.4% boys) entered the study between November 2021 and March 2022. We administered an online survey containing the Difficulties in Emotion Regulation Scale, Intolerance of Uncertainty Scale-Revised, Self-Administered Psychiatric Scales for Children and Adolescents-Anxiety scale, and Depression Anxiety Stress Scales-21. Pearson’s correlations were calculated to examine the relation between intolerance of uncertainty, emotion dysregulation dimensions, and different anxiety symptoms. A hierarchical linear regression was performed to test the predictive role of intolerance of uncertainty and specific emotion regulation strategies on generalized anxiety symptoms. Results: All emotion dysregulation dimensions, except Awareness, were significantly correlated with intolerance of uncertainty and the different anxiety manifestations. Intolerance of uncertainty was associated with all anxiety symptoms, but to a greater extent with generalized and school-related anxiety. Finally, both intolerance of uncertainty and specific emotion dysregulation dimensions (i.e., Goals and Strategies) predicted generalized anxiety symptoms; however, the emotion dysregulation block led to a higher increase in explained variance than intolerance of uncertainty did. Conclusion: Intolerance of uncertainty, emotion dysregulation, and anxiety symptoms emerged to be strictly associated. Moreover, the contribution of both intolerance of uncertainty and specific emotion regulation difficulties to the putative development of generalized anxiety in adolescence has been tentatively supported. Particularly, emotion dysregulation seems to play a more relevant role in generalized anxiety compared to intolerance of uncertainty

SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008-2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming ana priorigenetic model: step 1) a machine learning technique [Gradient Boosting Machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step 2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation

Antimeningococcal and antipneumococcal vaccination determinants: A European systematic literature review

EACKGROUND: ESCULAPIO is a multicenter project, funded by the Italian Centre for Disease Prevention and Control, aimed at implementing communication strategies to improve vaccination knowledge and attitudes among different target populations. OBJECTIVE: The objective of the Sicilian research unit was, in the first phase, to identify, through systematic literature revision, which vaccination determinants play a role in the uptake of recommended vaccines included in the Italian Vaccination Plan. DESIGN: A systematic literature review was carried out on studies describing the determinants underlying pneumococcal and meningococcal vaccination uptake. The analysis was limited to papers published in English from 2000 to date. RESULTS: A total of 188 (meningococcal) and 731 (pneumococcal) papers were found. After selection by publication data, country (Europe), article type (original article), target population (healthy subjects), 7 (meningococcal) and 4 ( pneumococcal) manuscripts were finally included in the analysis. For meningococcal vaccination a better socioeconomic status is related to vaccination acceptance, whereas distance from immunization service is a negative determinant. For pneumococcal vaccination the determinants related to vaccination uptake are older parental age and a strong vaccine recommendation. Conversely, when the vaccine needs to be paid for, a refusal is more likely. CONCLUSIONS: Our results show that payment for vaccination is a major barrier and communication about meningococcal and pneumococcal vaccination should be targeted towards specific population groups, especially through the counseling activities by health professionals

Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer's disease models

Abstract Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer's disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26–36aa of tau protein) could improve the Alzheimer's disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer's disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20–22 kDa NH2-terminal tau fragment is crucial target for Alzheimer's disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloidβ-dependent and independent neuropathological and cognitive alterations in affected subjects

Validation of PARADISE 24 and Development of PARADISE-EDEN 36 in Patients with Dementia

Dementia was one of the conditions focused on in an EU (European Union) project called “PARADISE” (Psychosocial fActors Relevant to brAin DISorders in Europe) that later produced a measure called PARADISE 24, developed within the biopsychosocial model proposed in the International Classification of Functioning Disability and Health (ICF). The aims of this study are to validate PARADISE 24 on a wider sample of patients with mild to moderate dementia to expand PARADISE 24 by defining a more specific scale for dementia, by adding 18 questions specifically selected for dementia, which eventually should be reduced to 12. We enrolled 123 persons with dementia, recruited between July 2017 and July 2019 in home care and long-term care facilities, in Italy, and 80 participants were recruited in Warsaw between January and July 2012 as part of a previous cross-sectional study. The interviews with the patient and/or family were conducted by health professionals alone or as a team by using the Paradise data collection protocol. The psychometric analysis with the Rasch analysis has shown that PARADISE 24 and the selection of 18 additional condition-specific items can be expected to have good measurement properties to assess the functional state in persons with dementia

An integrated approach identifies new oncotargets in melanoma

Melanoma is an aggressive skin cancer; an early detection of the primary tumor may improve its prognosis. Despite many genes have been shown to be involved in melanoma, the full framework of melanoma transformation has not been completely explored. The characterization of pathways involved in tumor restraint in in vitro models may help to identify oncotarget genes. We therefore aimed to probe novel oncotargets through an integrated approach involving proteomic, gene expression and bioinformatic analysis We investigated molecular modulations in melanoma cells treated with ascorbic acid, which is known to inhibit cancer growth at high concentrations. For this purpose a proteomic approach was applied. A deeper insight into ascorbic acid anticancer activity was achieved; the discovery of deregulated processes suggested further biomarkers. In addition, we evaluated the expression of identified genes as well as the migration ability in several melanoma cell lines. Data obtained by a multidisciplinary approach demonstrated the involvement of Enolase 1 (ENO1), Parkinsonism-associated deglycase (PARK7), Prostaglansin E synthase 3 (PTGES3), Nucleophosmin (NPM1), Stathmin 1 (STMN1) genes in cell transformation and identified Single stranded DNA binding protein 1 (SSBP1) as a possible onco-suppressor in melanoma cancer