New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Maternity Blues: A Narrative Review

Puerperium is a period of great vulnerability for the woman, associated with intense physical and emotional changes. Maternity blues (MB), also known as baby blues, postnatal blues, or post-partum blues, include low mood and mild, transient, self-limited depressive symptoms, which can be developed in the first days after delivery. However, the correct identification of this condition is difficult because a shared definition and well-established diagnostic tools are not still available. A great heterogenicity has been reported worldwide regarding MB prevalence. Studies described an overall prevalence of 39%, ranging from 13.7% to 76%, according to the cultural and geographical contexts. MB is a well-established risk factor for shifting to more severe post-partum mood disorders, such as post-partum depression and postpartum psychosis. Several risk factors and pathophysiological mechanisms which could provide the foundation of MB have been the object of investigations, but only poor evidence and speculations are available until now. Taking into account its non-negligible prevalence after childbirth, making an early diagnosis of MB is important to provide adequate and prompt support to the mother, which may contribute to avoiding evolutions toward more serious post-partum disorders. In this paper, we aimed to offer an overview of the knowledge available of MB in terms of definitions, diagnosis tools, pathophysiological mechanisms, and all major clinical aspects. Clinicians should know MB and be aware of its potential evolutions in order to offer the most timely and effective evidence-based care

Creazione di servizi personalizzati su dispositivi Android nell'ambito dell'Internet of Things collaborativo

In un mondo dove ormai qualunque oggetto quotidiano è connesso ad Internet ed è comune sentir parlare di “quarta rivoluzione industriale”, diventa critica la gestione dell'eterogeneità di dati prodotti dai dispositivi nell'ambito dell'Internet of Things. Perché non utilizzare tali informazioni in modo vantaggioso, integrandole tra loro a favore della città e dei suoi abitanti? Questa tesi focalizza l'attenzione sulla creazione di servizi personalizzati dalla combinazione di dati ufficiali e non, provenienti da sensori di stazioni di monitoraggio o di smartphone, a disposizione di utenti privati e di stakeholders. Le azioni svolte in merito sono state il reperimento di dati ufficiali dall’Arpae dell’Emilia-Romagna e la progettazione e sviluppo di Habitatest, un'applicazione mobile per il sistema Android. Habitatest offre ai suoi utenti un widget per visualizzare i valori dei dati, estratti da dispositivi di utenti privati, e dei servizi creati, un grafico che mostra l’andamento delle informazioni ed un sistema drag and drop per comporre tali dati, con una formula matematica, finalizzati alla produzione di servizi. L’obiettivo del progetto realizzato è stimolare gli utenti alla condivisione di dati, derivanti dai sensori dei propri dispositivi, ed alla creazione di servizi per scopi comuni, quali migliorare la qualità di vita di se stessi e delle altre persone, applicato a campi come la domotica, contribuire alla nascita delle Smart Cities e risparmiare risorse, salvaguardando l'ambiente in cui viviamo

Prevention of Preterm Birth with Progesterone

Gestational age at birth is a critical factor for perinatal and adulthood outcomes, and even for transgenerational conditions’ effects. Preterm birth (PTB) (prematurity) is still the main determinant for infant mortality and morbidity leading cause of infant morbidity and mortality. Unfortunately, preterm birth (PTB) is a relevant public health issue worldwide and the global PTB rate is around 11%. The premature activation of labor is underlined by complex mechanisms, with a multifactorial origin influenced by numerous known and probably unknown triggers. The possible mechanisms involved in a too early labor activation have been partially explained, and involve chemokines, receptors, and imbalanced inflammatory paths. Strategies for the early detection and prevention of this obstetric condition were proposed in clinical settings with interesting results. Progesterone has been demonstrated to have a key role in PTB prevention, showing several positive effects, such as lower prostaglandin synthesis, the inhibition of cervical stromal degradation, modulating the inflammatory response, reducing gap junction formation, and decreasing myometrial activation. The available scientific knowledge, data and recommendations address multiple current areas of debate regarding the use of progesterone in multifetal gestation, including different formulations, doses and routes of administration and its safety profile in pregnancy

COVID-19 vaccination in pregnancy and postpartum

: Pregnant women were excluded from the initial phase 3 clinical trials of COVID-19 vaccines resulting in limited data on their efficacy and safety during pregnancy and postpartum. As a result, since December 2020, there has been conflicting advice from public health, governmental, and professional authorities on this matter. From the end of 2020 up to now, some consensus guidance has been published with a prevalent precautionary approach on the administration of vaccines in pregnant women, in breastfeeding ones, or for those who are planning a pregnancy (either spontaneously or with assisted technologies). After the first few months of vaccine administration in some countries, more permissiveness seems to prevail, although with inconsistencies. Some little indicative advice, their inconsistency around the world and their changes in a short time have probably disoriented both women and their health care providers and placed the burden of decision making upon women and their health care providers without information to assist in making an informed choice. We reviewed the COVID-19 vaccination guidance for pregnant and breastfeeding women published to date and evidence from cases of unplanned pregnancy during the course of vaccine trials, preclinical experimental and observational clinical studies, and discuss their implications. In this way, we have tried to identify the safety of COVID-19 vaccines for pregnant or breastfeeding women, and their offspring

Exploring Tdap and influenza vaccine uptake and its determinants in pregnancy: a cross-sectional study

Background. The literature claims that an increased risk of complications from pertussis and influenza exists for pregnant women and infants. Maternal tetanus, diphtheria, and acellular pertussis (Tdap) and influenza vaccines seem to decrease this risk so that several countries are committed to increase vaccination uptake, but not all of them know their own vaccination coverage and factors that motivate this population to vaccination.Study Design. A cross-sectional survey was conducted.Methods. We conducted this survey to estimate among pregnant women: 1) the vaccine coverage, 2) the availability of information, 3) the knowledge about maternal Tdap and influenza vaccination, 4) the factors that could have driven unvaccinated pregnant women to have themselves vaccinated. In addition, determinants of Tdap and influenza vaccine uptake and correct knowledge about vaccine-preventable diseases and vaccination in pregnancy were assessed using univariate and multivariate analyses.Results. Of the 250 women included in the present study, only 58 (23.2%, 95% Confidence Interval (CI): 18-28.4%) and 21 (8.1%, 95% CI: 5-11.8%) reported that they had been vaccinated with Tdap and influenza vaccine, respectively, during their current pregnancy. The most common reasons cited for getting themselves vaccinated was having background knowledge of the health problems due to the diseases prevented by Tdap and influenza vaccines, awareness regarding these vaccines being recommended in pregnancy, knowledge of their effectiveness and/or side effects, and having been informed about vaccination by a healthcare professional.Conclusions. Influenza and Tdap vaccine uptake among pregnant women in Italy is low, however, the present study showed that women are available to get vaccinated during pregnancy when adequately informed about the vaccines recommended

Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy

Polymeric cyclodextrin–based nanoparticles are currently undergoing clinical trials as nanotherapeutics. Using a non-covalent approach, we decorated two cross-linked cyclodextrin polymers of different molecular weights with an RGD peptide derivative to construct a novel carrier for the targeted delivery of doxorubicin. RGD is the binding sequence for the integrin receptor family that is highly expressed in tumour tissues. The assembled host–guest systems were investigated using NMR and DLS techniques. We found that, in comparison with free doxorubicin or the binary complex doxorubicin/cyclodextrin polymer, the RGD units decorating the cyclodextrin-based nanosystems improved the selectivity and cytotoxicity of the complexed doxorubicin towards cultured human tumour cell lines. Our results suggest that the nanocarriers under study may contribute to the development of new platforms for cancer therapy

Risk factors for non-adherent retained placenta after vaginal delivery: a systematic review

Background Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes difficult to develop predictive and preventive strategies to apply in clinical practice. This analysis collected and analyzed all known risk factors related to this obstetric complication. Methods A systematic literature review for all original research articles published between 1990 and 2020 was performed. Observational studies about retained placenta risk factors published in English language were considered eligible. Conference abstracts, untraceable articles and studies focused on morbidly adherent placenta were excluded. The included articles were screened to identify study design, number of enrolled patients and retained placenta risk factors investigated. All stages of the revision followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Results Thirty-five studies met the inclusion criteria. The reported retained placenta prevalence ranged from 0.5 to 4.8%. Maternal age, previous cesarean sections, previous dilation and curettage, previous retained placenta, labor induction, resulted as the most recurrent, independent risk factors for retained placenta. Previous estro-progestins therapy, morphological placental features (weight, shape, insertion of umbilical cord, implantation site), endometriosis, Assisted Reproductive Technologies, Apgar score are fascinating new proposal risk factors. Conclusions Old and new data are not enough robust to draw firm conclusions. Prospective and well-designed studies, based on a well agreed internationally retained placenta definition, are needed in order to clarify this potential dramatic and life-threatening condition

Maternity Blues: A Narrative Review

Puerperium is a period of great vulnerability for the woman, associated with intense physical and emotional changes. Maternity blues (MB), also known as baby blues, postnatal blues, or post-partum blues, include low mood and mild, transient, self-limited depressive symptoms, which can be developed in the first days after delivery. However, the correct identification of this condition is difficult because a shared definition and well-established diagnostic tools are not still available. A great heterogenicity has been reported worldwide regarding MB prevalence. Studies described an overall prevalence of 39%, ranging from 13.7% to 76%, according to the cultural and geographical contexts. MB is a well-established risk factor for shifting to more severe post-partum mood disorders, such as post-partum depression and postpartum psychosis. Several risk factors and pathophysiological mechanisms which could provide the foundation of MB have been the object of investigations, but only poor evidence and speculations are available until now. Taking into account its non-negligible prevalence after childbirth, making an early diagnosis of MB is important to provide adequate and prompt support to the mother, which may contribute to avoiding evolutions toward more serious post-partum disorders. In this paper, we aimed to offer an overview of the knowledge available of MB in terms of definitions, diagnosis tools, pathophysiological mechanisms, and all major clinical aspects. Clinicians should know MB and be aware of its potential evolutions in order to offer the most timely and effective evidence-based care

Metastatic Breast Neuroendocrine Cancer in Pregnancy: A Case of an Oncologic Emergency and a Review of Literature

Breast neuroendocrine carcinoma is a rare entity. It constitutes less than 0.5% of breast malignancies, and is usually diagnosed in older women. The occurrence of this type in young patients during pregnancy is extremely rare. Only 2 cases were previously reported. Both were diagnosed at earlier stage with the appearance of a palpable breast mass. Hereby, we present the case of a young patient at 28 weeks’ gestation admitted for severe diffuse back pain and neurologic deficit due to spinal cord compression at the level of C5 vertebra, and nerve root compression at the level of L5 vertebrae. To the best of our knowledge, this is the first case of oncologic emergency during pregnancy due to a metastatic poorly differentiated breast carcinoma with neuroendocrine differentiation in the absence of a detectable primary focus of malignancy in the breast. We also discuss the management and the obstetrical outcome of this patient.SCOPUS: re.jDecretOANoAutActifinfo:eu-repo/semantics/publishe