Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients

Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology

New human milk fortifiers for the preterm infant

Given its unique nutritional and functional advantages, human milk (HM) should be considered as the first choice for the nutrition of all infants, including preterm newborns. Since its protein, mineral and energy contents are not suitable to meet the high needs of very-low-birth-weight (VLBW) infants, HM should be fortified for these components. Fortification of HM is an important nutritional intervention in order to provide appropriate nutritional intake and appropriate growth. The standard fortification strategy has yielded inadequate protein intakes, resulting in slower growth as compared to preterm formulas. Improvement of outcomes depends on new fortification strategies, considering the large variability of HM composition. Individualized fortification, either targeted or adjustable, has been shown to be effective and practical in attaining adequate protein intakes and growth.<br />Most commercially available multi-nutrient fortifiers and protein concentrates are derived from bovine milk (BM), which has a protein composition very different from that of HM. The use of BM proteins has been recently questioned for possible association with intestinal inflammation in VLBW infants. Recently, one HM-based fortifier was shown to be associated with lower necrotizing enterocolitis rates and lower mortality in extremely premature infants, compared to BM-based products. Other milk sources are currently under evaluation: a randomized, controlled, single-blind clinical trial, coordinated by the Neonatal Unit of the University of Turin in collaboration with the Italian National Research Council of Turin and the University of Cagliari, is being carried out to evaluate the adequacy of fortifiers derived from donkey milk for the nutrition of preterm infants

Integrated production of biopolymers with industrial wastewater treatment: Effects of OLR on process yields, biopolymers characteristics and mixed microbial community enrichment

The production of polyhydroxyalkanoates (PHA) using industrial wastewaters as feedstocks is a current and challenging topic. This study investigated the production of biopolymers by a mixed microbial culture under different OLRs equal to 1 kgCOD m-3d-1 (Period 1), 2 kgCOD m-3d-1 (Period 2) and 3 kgCOD m-3d-1 (Period 3). The maximum PHA content was achieved in Period 2 (0.38 gPHA gTSS-1), whereas lower values were obtained in Period 1 (0.13 gPHA gTSS-1) and Period 3 (0.26 gPHA gTSS-1). Overall, the maximum PHA productivity resulted equal to 0.08 gPHA L-1h-1 (P2), 0.05 gPHA L-1h-1 (P1) and 0.04 gPHA L-1h-1 (P3), respectively. The molecular weight of the PHA increased from Period 1 (250 kDa) to Period 2 (417 KDa) and Period 3 (463 KDa), although resulting in a slight decrease of crystallinity degree. Microbial community analysis, revealed a reduction in bacterial diversity and a progressive shift of the microbial community with the increasing OLR. Alpha-diversity indexes based on Operational Taxonomic Units (OTUs) at 99% identity revealed higher species richness (Taxa (S) 280) and diversity (Shannon (H) 4,06) in Period 1, whereas Period 3 was characterized by reduced richness and diversity and higher dominance (Taxa (S) 133, Shannon (H) 2,40). Based on the results obtained, it was pointed out that the OLR variation determined significant effects on the process performances, as well as on the productivity and quality of the biopolymers. This means that OLR is a key control parameter to maximize the PHA production and control the physical-chemical characteristics of the polymers

Magnesium homeostasis goes awry in chemoresistance -TRPM6, TRPM7 and MagT1 in colon carcinoma LoVo cells

Chemoresistance is one of the most significant factors impeding the progress of cancer therapy (1). It is known that neoplastic cells accumulate magnesium and frequently upregulate one of its transporters, i.e.TRPM7 (2). We have investigated magnesium homeostasis in a model of chemoresistance i.e. colon carcinoma LoVo cells sensitive (LoVo-S) or resistant to doxorubicin (LoVo-R). We observed that LoVo-R have higher amount of total intracellular magnesium than LoVo-S. We studied the expression of some magnesium transporter (TRPM6, TRPM7 and MagT1) by Real Time PCR and Western Blot and found that TRPM6 and 7 are overexpressed in LoVo-S, while MagT1 is upregulated in LoVo-R. In LoVo-S, silencing TRPM7 retards cell growth and shifts the phenotype to one more similar to resistant cells. On the other hand, calpeptin, a calpain inhibitor, upregulates TRPM7, stimulated proliferation and enhances the sensitivity to doxorubicin of LoVo-R. Silencing MagT1 in LoVo-R markedly inhibited cell growth without affecting the response to doxorubicin. We conclude that alterations of magnesium homeostasis play a role in drug resistance

Sensitivity of three commercial tests for SARS-CoV-2 serology in children: an Italian multicentre prospective study

US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. Methods: Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value &lt; 0.05 indicated statistical significance. Results: Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15-28 days from infection (0.94, 95%CI: 0.73-1.0) and Roche N at 28-84 days (0.78, 95%CI: 0.58-0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests. Conclusion: Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests

La presa in carico della persona anziana vittima di maltrattamento: analisi del fenomeno in due contesti di emergenza di Regione Lombardia

BACKGROUND: Il maltrattamento della persona anziana è un fenomeno sottostimato, rappresenta una violazione dei diritti umani e un grave problema di salute globale che espone le vittime a pesanti conseguenze per la salute. Si stima che nei prossimi decenni le violenze sugli anziani siano destinate a crescere. OBIETTIVO: Indagare l’esperienza degli Infermieri del Pronto Soccorso di due contesti ospedalieri riguardo alla violenza contro gli anziani. METODI: È stata condotta un’indagine somministrando un questionario costruito partendo da un precedente studio realizzato dall’Università degli studi di Urbino. È stato selezionato un campione di convenienza sul gruppo di Infermieri afferenti alle due strutture regionali di Pronto Soccorso. RISULTATI: Sono stati reclutati 117 Infermieri, 41 (35%) hanno risposto al questionario. La forma di violenza maggiormente riscontrata è la negligenza, seguita da violenza psicologica, fisica, economica e sessuale. Età avanzata e non autosufficienza sono stati riconosciuti come fattori di rischio predisponenti alla violenza; mentre sembra che appartenere al genere femminile non predisponga ad agiti annoverabili come violenza. Tra gli autori del maltrattamento la vicinanza abitativa o affettiva sono elementi da considerare predisponenti; i familiari intimi o i caregiver sono spesso autori del reato. Appare significativa la percentuale degli operatori socio- sanitari (4%). CONCLUSIONI: La violenza e il maltrattamento contro la persona anziana sono argomenti poco esplorati, talvolta considerati una problematica assistenziale piuttosto che una riflessione della Comunità Scientifica Infermieristica. Risulta indispensabile adeguare i programmi formativi ai vari livelli in quest’ambito e sviluppare un modello di presa in carico condiviso basato sulla valutazione oggettiva del rischioBACKGROUND: Elderly maltreatment is an underestimated phenomenon, represents a human rights violation and a serious global health problem that exposes victims to heavy health consequences. We estimate that violence against the elderly is likely to increase in the coming decades. AIM: To investigate the Emergency Room Nurses experiences in two hospital regarding elderly violence. METHODS: The survey was conducted by administering a questionnaire revised from an earlier study performed by the University of Urbino. A convenience sample was selected on the group of nurses attached to the two regional Emergency Room facilities. RESULTS: A total of 117 nurses were recruited, 41 (35%) responded to the questionnaire. The most frequently encountered violence form is neglect, followed by psychological, physical, economic, and sexual violence. Advanced age and non-self-sufficiency were recognized as predisposing risk factors for violence, while it appears that belonging to the female gender does not predispose to acts that can be counted as violence. Among maltreatment perpetrators, living or emotional proximity is a predisposing element; close family members or caregivers are often the crime perpetrators. The social-health workers percentage (4 percent) appears significant. CONCLUSIONS: Elderly violence and mistreatment are still under-explored topics, sometimes considered a care issue rather than a consideration to be addressed in the Nursing Scientific Community. Adapting training programs regarding the elderly violence management and the development of a shared intake model based on objective risk assessment is essential

Gravidez não planejada no Brasil: estudo nacional em oito hospitais universitários

OBJECTIVE: To estimate the prevalence of unplanned pregnancy in eight public university hospitals, distributed in the five regions that make up Brazil. METHODS: A secondary analysis of a national multicenter cross-sectional study, carried out in eight public university hospitals between June 1 and August 31, 2020, in Brazil. Convenience sample including women who gave birth within sixty consecutive days and met the following criteria: over 18 years old; gestational age over 36 weeks at delivery; with a single and live newborn, without malformations. RESULTS: Sample composed of 1,120 postpartum women, of whom 756 (67.5%) declared that the pregnancy had not been planned. The median prevalence of unplanned pregnancy was 59.7%. The prevalence of unplanned pregnancy across hospitals differed significantly: Campinas (54.8%), Porto Alegre (58.2%), Florianópolis (59%), Teresina (61.2%), Brasília (64.3%), São Paulo (64.6%), Campo Grande (73.9%) and Manaus (95.3%) (p &lt; 0.001). Factors significantly associated with unplanned pregnancy were maternal age, black color, lower family income, greater number of children, greater number of people living in household, and not having a partner. CONCLUSION: In the studied sample, about two thirds of the pregnancies were declared as unplanned. The prevalence of unplanned pregnancies was related to social and demographic factors and varied significantly across the university hospitals evaluated.OBJETIVO: Estimar a prevalência de gestação não planejada (GNP) em oito hospitais públicos universitários, distribuídos nas cinco regiões que compõem o Brasil. MÉTODOS: Análise secundária de um estudo transversal multicêntrico nacional, realizado em oito hospitais universitários públicos, entre 1º de junho e 31 de agosto de 2020, no Brasil. Amostra por conveniência incluindo mulheres que deram à luz em período de sessenta dias consecutivos e atenderam aos seguintes critérios: maiores de 18 anos; idade gestacional acima de 36 semanas no parto; com recém-nascido único e vivo, sem malformações. RESULTADOS: Amostra composta por 1.120 puérperas, das quais 756 (67,5%) declararam que a gravidez não tinha sido programada. A mediana da prevalência de GNP foi de 59,7%. Observou-se diferença significativa na prevalência de GNP entre os hospitais: Campinas (54,8%), Porto Alegre (58,2%), Florianópolis (59%), Teresina (61,2%), Brasília (64,3%), São Paulo (64,6%), Campo Grande (73,9%) e Manaus (95,3%) (p &lt; 0,001). Foram fatores significativamente associados a GNP a idade materna, cor negra, menor renda familiar, maior número de filhos, maior número de pessoas convivendo em casa e não ter parceiro. CONCLUSÃO: na amostra estudada, cerca de dois terços das gestações foram declaradas como não programadas. A prevalência de gestação não planejada teve relação com fatores sociais e demográficos e variou significativamente entre os hospitais universitários avaliados

Aumento do risco de ansiedade materna durante o surto de covid-19 no Brasil entre gestantes sem comorbidades

Objective: To studymaternal anxiety in pregnant womenwithout comorbidities in the context of the COVID-19 outbreak in Brazil and to study maternal knowledge and concerns about the pandemic. Methods: This is a secondary analysis from a national multicenter cross-sectional study performed in 10 cities, from June to August, 2020, in Brazil. Interviewed postpartum women, without medical or obstetrical comorbidities, were included in the present subanalysis. A structured questionnaire and the Beck Anxiety Inventory (BAI) were applied. Results: Out of the 1,662 women, 763 (45.9%)met the criteria for the current analysis and 16.1% presentedwithmoderate and 11.5% with severe maternal anxiety. Moderate or severe maternal anxiety was associated with high school education (odds ratio [OR]:1.58; 95% confidence interval [CI]:1.04–2.40). The protective factor was cohabiting with a partner (OR: 0.46; 95%CI: 0.29–0.73). There was a positive correlation between the total BAI score and receiving information about care in the pandemic (rpartial 0.15; p<0.001); concern about vertical transmission of COVID-19 (rpartial 0.10; p=0.01); receiving information about breastfeeding (rpartial 0.08; p¼0.03); concerns about prenatal care (rpartial 0.10; p¼0.01), and concerns about the baby contracting COVID-19 (rpartial 0.11; p=0.004). The correlation was negative in the following aspects: self-confidence in protecting from COVID-19 (rpartial 0.08; p¼0.04), having learned (rpartial 0.09; p=0.01) and self-confidence in breastfeeding (rpartial 0.22; p<0.001) in the context of the pandemic. Conclusion: The anxiety of pregnant women without medical or obstetrical comorbidities was associated to high school educational level and not living with a partner during the COVID-19 pandemic. Self-confidence in protecting against COVID-19 and knowledge about breastfeeding care during the pandemic reduced maternal anxiety.Objetivo: Estudar a ansiedade materna em gestantes sem comorbidades no contexto do surto de COVID-19 no Brasil e estudar o conhecimento e as preocupações maternas sobre a pandemia. Métodos: Trata-se de análise secundária de um estudo transversal multicêntrico nacional realizado em 10 cidades, de junho a agosto de 2020, no Brasil. Mulheres no pós-parto entrevistadas, semcomorbidadesmédicas ou obstétricas, foramincluídas nesta subanálise. Foram aplicados um questionário estruturado e o Inventário de Ansiedade de Beck (BAI, na sigla em inglês). Resultados: Das 1.662 mulheres, 763 (45,9%) atenderam aos critérios da análise atual e 16,1% apresentaram ansiedade materna moderada e 11,5% ansiedade materna grave. A ansiedade materna moderada ou grave foi associada à escolaridade no ensino médio (odds ratio [OR]: 1,58; intervalo de confiança [IC] 95%: 1,04–2,40). O fator protetor foi coabitar com companheiro (OR: 0,46; IC95%: 0,29–0,73). Houve correlação positiva entre a pontuação total do BAI e o recebimento de informações sobre cuidados na pandemia (rparcial 0,15; p<0,001); preocupação com a transmissão vertical de COVID-19 (rparcial 0,10; p=0,01); receber informações sobre amamentação (rparcial 0,08; p=0,03); preocupações sobre cuidados pré-natais (rparcial 0,10; p=0,01) e preocupações sobre o bebê contrair COVID-19 (rparcial 0,11; p=0,004). A correlação foi negativa com os seguintes aspectos: ter autoconfiança para se proteger (rparcial 0,08; p=0,04), aprender (rparcial 0,09; p=0,01) e ter autoconfiança para amamentar (rparcial 0,22; p<0,001) no contexto da pandemia. Conclusão: A ansiedade de gestantes sem comorbidades médicas ou obstétricas esteve associada à escolaridade no ensino médio e não morar com companheiro durante a pandemia de COVID-19. A autoconfiança na proteção contra COVID-19 e o conhecimento sobre os cuidados com a amamenta