Cellular gene delivery via poly(hexamethylene biguanide)/pDNA self-assembled nanoparticles.

Cellular gene delivery via polycations has wide implications for the potential of gene therapy, but it has remained a challenge due to the plethora of pre- and post-uptake barriers that must be overcome to reach desired efficiency. Herein we report poly(hexamethylene biguanide) (PHMB) as a nano-vector for intracellular delivery of plasmid DNA (pDNA) and oligodeoxynucleotides (ODNs). PHMB and pDNA or ODNs self-assembled into complex nanoparticles at different pH values (7.4 and 12). Their size, charge, cellular uptake, and gene-expression efficiency are assessed and compared to PEI analogues. The systematic results show that the nanoparticles are effective in delivering plasmid DNA and ODNs to model cell lines in culture (HepG2, HEK293T, HeLa), with measurable changes in gene expression levels, comparable to and, in some conditions, even higher than PEI. The well-accepted safety profile of PHMB makes it a valuable candidate for consideration as an effective intracellular DNA vector for further study and potential clinical translation.

National-survey for evaluation of the best screening method of late fetal growth restriction in low risk pregnancy: A prospective study.

OBJECTIVE: To compare knowledge and practices surrounding third trimester screening of fetal growth restriction (FGR) in low risk pregnancies among Portuguese Gynecologists/Obstetricians (GOs) and General Practitioners (GPs). Primary outcome was to compare the proportion of GOs that consider the need of a third trimester ultrasound (estimation of fetal weight) for screening of FGR in low risk pregnancies and the best time to perform it with the corresponding proportion of GPs. STUDY DESIGN: We have conducted a prospective, observational cohort study based on application of surveys to GOs and GPs. Questionnaires were sent by e-mail to physicians and they filled them online. A second reminder e-mail was sent 7 days later. Recruitment was also done personally at scientific meetings. A total of 573 surveys were available for analysis, 298 corresponded to GOs and 275 to GPs. We used χ2 test to compare dichotomous variables and Kruskal-Wallis test for the comparison of ordinal variables. P values <0.05 were considered statistically significant. RESULTS: The vast majority of GOs and GPs (93%) considered that third trimester ultrasound is useful and needed for surveillance of low risk pregnancy. A higher proportion of GOs (38%) selected 35th-37th weeks as the best time to perform the ultrasound compared to GPs (10%) (p < 0.001). GOs (51%) consider that symphysis-fundus distance is a measurement with moderate accuracy for screening of FGR while GPs (61%) attribute a low accuracy (p < 0.001). Fifty percent (50%) of GOs consider that performing a third trimester ultrasound will have no impact on cesarean delivery rate for fetal distress, while 41% of GPs consider that routine ultrasound will contribute to increase this rate (p < 0.001). The majority of GPs (52%) consider that routine ultrasound will contribute to diminish the admission rate to neonatal intensive care unit while GOs revealed a dichotomy with 43% of respondents reporting that it will diminish the rate and 40% that it will have no impact. CONCLUSION: Varied opinions among the clinicians included in our sample reflect the controversy that remains on the best screening of FGR in low risk pregnancies.

[Twin pregnancy with a complete hydatiform mole and a viable co-twin]. / Gravidez gemelar com uma mola hidatiforme completa e um co-gémeo viável.

A complete hydatiform mole coexisting with a live, viable twin is a rare event. The diagnosis is challenging, and is normally achieved only at second trimester. It may be associated with thyrotoxicosis, vaginal bleeding, preeclampsia, fetal death or persistent throphoblastic disease. The authors describe the case of a pregnant woman presenting with first trimester bleeding. Ultrasound revealed a twin pregnancy with a viable twin and another placenta apparently detached. At 16 gestational weeks ultrasound revealed a live fetus with a normal placenta and a separate vacuolated and vascularized mass. Facing the hypothesis of gestational trophoblastic disease, the couple chose pregnancy interruption. Given the rarity of this situation, a high index of suspicion is needed to achieve the diagnosis. Despite the existence of case reports with good fetal and maternal outcome, the decision of pregnancy continuation should be made by the informed parents.

A existência de uma gravidez gemelar bicoriónica com uma mola hidatiforme completa e um co-gémeo viável é um evento raro, sendo o diagnóstico habitualmente realizado no segundo trimestre. Pode associar-se a tirotoxicose, pré-eclâmpsia, hemorragia vaginal, doença persistente do trofoblasto e morte fetal. Os autores descrevem o caso de uma grávida com hemorragia do primeiro trimestre. As imagens ecográficas foram interpretadas como uma gravidez gemelar bicoriónica com um embrião vivo e outra placenta com imagem de descolamento. Às 16 semanas visualizou-se um feto vivo com placenta posterior e uma massa vacuolada anterior, vascularizada. Perante a hipótese de doença do trofoblasto o casal optou pela interrupção da gravidez. O exame anatomo-patológico confirmou o diagnóstico. Perante a raridade desta entidade clínica, é necessário um elevado índice de suspeição para estabelecer oseu diagnóstico ecográfico. Apesar de estarem descritos casos com um bom desfecho materno e neonatal, a decisão de continuação da gravidez deve ser tomada pelos progenitores.

Maternal and neonatal immediate effects of sequential delivery.

OBJECTIVE: To evaluate the immediate maternal and neonatal outcomes associated with sequential instrumental delivery (vacuum plus forceps) compared with the use of one instrument only (forceps or vacuum). STUDY DESIGN: A longitudinal observational study was carried out, including all instrumental deliveries performed in term singleton pregnancies, in vertex presentation, at station level 0 or +1. According to the type of the instruments, the deliveries were divided in three groups: the vacuum group, the forceps group and the sequential group. Immediate maternal and neonatal outcomes were evaluated. RESULTS: A total of 275 instrumental deliveries were performed: 126 (45.5%) vacuum assisted deliveries, 62 (22.6%) forceps assisted deliveries and 87 (31.6%) sequential deliveries. Regarding maternal morbidity, there was a significant difference between the three groups (p < 0.001), with a higher rate of complications in the sequential group. The type of instrument was the only factor associated with significant maternal morbidity. The rate of immediate neonatal morbidity was 4.4% and there was no significant association with the instrument type or with other identifiable factors. CONCLUSION: Sequential delivery is associated with a higher maternal morbidity and it seems not to increase neonatal morbidity.

[Systemic lupus erythematosus and pregnancy]. / Lupus eritematoso sistémico e gravidez.

Systemic lupus erythematosus is a chronic inflammatory disease, resulting from an auto-immune dysfunction. The etiology of this disease is unknown. It frequently occurs in women of childbearing age. Pregnancy in patients with systemic lupus erythematosus may be associated with several complications (maternal, obstetrical and fetal). The prognosis for both mother and child is better when systemic lupus erythematosus has been quiescent for at least six months before pregnancy. Thus, preconceptional assessment and management is crucial for helping women to achieve a period of disease remission before pregnancy as well as for allowing an adjustment of therapy. Maternal health and fetal development should be closely monitored during pregnancy. These patients should be surveilled by a multidisciplinary team (obstetrician, rheumatologist or internist, nephrologist if necessary and a pediatrician), in a tertiary care hospital. Antiphospholipid syndrome, positivity for anti-SSA/Ro or anti-SSB/LA antibodies, hypertension or renal involvement are associated with an increase of adverse pregnancy outcomes. In this article the authors review the main aspects of Systemic lupus erythematosus (SLE) and pregnancy.