Removal vs. retention of cervical cerclage in pregnancies complicated by preterm premature rupture of membranes: a retrospective study.

PURPOSE: To compare pregnancy outcomes in women with pPROM and a cervical cerclage in whom the cerclage was removed within 24 h and those in whom the cerclage was retained in situ. METHODS: A two-center retrospective cohort study of women with a singleton gestation with pPROM at < 340/7 weeks of gestation in the presence of cervical cerclage (January 1, 2012-July 30, 2016). Maternal and perinatal outcomes were compared between women in whom cerclage was removed within 24 h from pPROM and those in whom cerclage was retained until the onset of delivery. The primary outcome was time from pPROM to delivery. RESULTS: Seventy women met inclusion criteria. Cerclage was left in situ in 47 (67.1%) and removed in 23 (32.9%) women. Women in the cerclage retention group had a higher pPROM-to-delivery interval (7.0 ± 7.2 vs. 6.0 ± 10.9 days, p = 0.03), and were more likely to have a latency period > 48 h (87.2% vs. 65.2%, p = 0.03; aOR 3.9, 95% CI 3.1-4.9) or > 7 days (29.8% vs. 8.7%, p = 0.04; aOR 7.0, 95% CI 2.5-19.6) compared with women in whom cerclage was removed. Furthermore, chorioamnionitis rate was lower in the cerclage retention group compared to cerclage removal group (aOR 0.7, 95% CI 0.5-1.0). There were no differences between the groups in early neonatal sepsis, severe brain injury, or composite neonatal outcome. CONCLUSION: In women with pPROM and cervical cerclage, retention of cerclage may be associated with a longer latency period, and a lower chorioamnionitis rate, without an associated increase in the risk of neonatal infectious morbidity. Presentation information: The abstract of this study was presented as a poster at the 38th SMFM (Society of Maternal and Fetal Medicine) annual meeting, February 2018, Dallas, Texas, USA.

Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich's Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress.

Adenosine is a nucleoside that is widely distributed in the central nervous system and acts as a central excitatory and inhibitory neurotransmitter in the brain. The protective role of adenosine in different pathological conditions and neurodegenerative diseases is mainly mediated by adenosine receptors. However, its potential role in mitigating the deleterious effects of oxidative stress in Friedreich's ataxia (FRDA) remains poorly understood. We aimed to investigate the protective effects of adenosine against mitochondrial dysfunction and impaired mitochondrial biogenesis in L-buthionine sulfoximine (BSO)-induced oxidative stress in dermal fibroblasts derived from an FRDA patient. The FRDA fibroblasts were pre-treated with adenosine for 2 h, followed by 12.50 mM BSO to induce oxidative stress. Cells in medium without any treatments or pre-treated with 5 µM idebenone served as the negative and positive controls, respectively. Cell viability, mitochondrial membrane potential (MMP), aconitase activity, adenosine triphosphate (ATP) level, mitochondrial biogenesis, and associated gene expressions were assessed. We observed disruption of mitochondrial function and biogenesis and alteration in gene expression patterns in BSO-treated FRDA fibroblasts. Pre-treatment with adenosine ranging from 0-600 µM restored MMP, promoted ATP production and mitochondrial biogenesis, and modulated the expression of key metabolic genes, namely nuclear respiratory factor 1 (NRF1), transcription factor A, mitochondrial (TFAM), and NFE2-like bZIP transcription factor 2 (NFE2L2). Our study demonstrated that adenosine targeted mitochondrial defects in FRDA, contributing to improved mitochondrial function and biogenesis, leading to cellular iron homeostasis. Therefore, we suggest a possible therapeutic role for adenosine in FRDA.

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review.

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs.

Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review.

BACKGROUND: Hereditary ataxia (HA) represents a group of genetically heterogeneous neurodegenerative diseases caused by dysfunction of the cerebellum or disruption of the connection between the cerebellum and other areas of the central nervous system. Phenotypic manifestation of HA includes unsteadiness of stance and gait, dysarthria, nystagmus, dysmetria and complaints of clumsiness. There are no specific treatments for HA. Management strategies provide supportive treatment to reduce symptoms. OBJECTIVES: This systematic review aimed to identify, evaluate and summarise the published literature on the therapeutic roles of natural remedies in the treatment of HA to provide evidence for clinical practice. METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed and Science Direct Scopus were thoroughly searched for relevant published articles from June 2007 to July 2020. RESULTS: Ten pre-clinical and two clinical studies were eligible for inclusion in this systematic review. We identified the therapeutic roles of medicinal plants Brassica napus, Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Paeonia lactiflora, Pueraria lobata and Rehmannia glutinosa; herbal formulations Shaoyao Gancao Tang and Zhengan Xifeng Tang; and medicinal mushroom Hericium erinaceus in the treatment of HA. In this review, we evaluated the mode of actions contributing to their therapeutic effects, including activation of the ubiquitin-proteasome system, activation of antioxidant pathways, maintenance of intracellular calcium homeostasis and regulation of chaperones. We also briefly highlighted the integral cellular signalling pathways responsible for orchestrating the mode of actions. CONCLUSION: We reviewed the therapeutic roles of natural remedies in improving or halting the progression of HA, which warrant further study for applications into clinical practice.

Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression.

BACKGROUND: Depression is a severe neuropsychiatric disorder that affects more than 264 million people worldwide. The efficacy of conventional antidepressants are barely adequate and many have side effects. Hericium erinaceus (HE) is a medicinal mushroom that has been reported to have therapeutic potential for treating depression. METHODS: Animals subjected to chronic restraint stress were given 4 weeks HE treatment. Animals were then screened for anxiety and depressive-like behaviours. Gene and protein assays, as well as histological analysis were performed to probe the role of neurogenesis in mediating the therapeutic effect of HE. Temozolomide was administered to validate the neurogenesis-dependent mechanism of HE. RESULTS: The results showed that 4 weeks of HE treatment ameliorated depressive-like behaviours in mice subjected to 14 days of restraint stress. Further molecular assays demonstrated the 4-week HE treatment elevated the expression of several neurogenesis-related genes and proteins, including doublecortin, nestin, synaptophysin, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated extracellular signal-regulated kinase, and phosphorylated cAMP response element-binding protein (pCREB). Increased bromodeoxyuridine-positive cells were also observed in the dentate gyrus of the hippocampus, indicating enhanced neurogenesis. Neurogenesis blocker temozolomide completely abolished the antidepressant-like effects of HE, confirming a neurogenesis-dependent mechanism. Moreover, HE induced anti-neuroinflammatory effects through reducing astrocyte activation in the hippocampus, which was also abolished with temozolomide administration. CONCLUSION: HE exerts antidepressant effects by promoting neurogenesis and reducing neuroinflammation through enhancing the BDNF-TrkB-CREB signalling pathway.

Spontaneously Resolved Macrocystic Lymphatic Malformations: Predictive Variables and Outcomes.

INTRODUCTION: Lymphatic malformations are benign, low-flow vascular malformations that typically present at or near birth. Due to morbidity associated with operative treatment, nonoperative treatment with injection of sclerosant has become the mainstay of therapy. Over the past 15 years, several patients at our centre with macrocystic (>2 cm cyst size) lymphatic malformations have seen their lesions resolve spontaneously while awaiting treatment. In this study, we review features of these patients that may contribute to spontaneous resolution. METHOD: A retrospective chart review was conducted from our Vascular Anomalies Clinic database (1999-2014) of all macrocystic lymphatic malformations; characteristics of patients with spontaneous resolution were reviewed. RESULTS: Of 61 patients with macrocystic lymphatic malformations, 7 cases (11.5%; 4 females, 3 males) resolved spontaneously. Median age at malformation appearance was 2 years (range: 0-6.5 years), with median age at resolution of 4 years (range: 10 months-7 years). Median time from appearance to resolution was 24 months (range: 3-43 months), with a median follow-up time of 4 years (range: 1-15 years). All but 1 case was associated with local or upper respiratory tract infection antecedent to resolution. Six of the 7 lesions were located in the neck. CONCLUSION: Among the cases reviewed, there was a common theme of upper respiratory tract or local infection antecedent to spontaneous lesion resolution. Compared to the literature, our proportion of malformations presenting after birth and the proportion of malformations presenting in the neck region were higher than those of other series. Although side effects associated with treatment are generally mild and/or rare, risks related to sclerotherapy and the accompanying requirement for general anesthesia in pediatric populations nevertheless exist. As the median time from lesion appearance to resolution was 24 months, it may be reasonable to observe these malformations for up to 24 months before proceeding with treatment if the lesion does not impair function and disfigurement is not considerable, particularly if the lesion presents after birth and/or is located in the neck region.

HISTORIQUE: Les malformations lymphatiques sont des malformations vasculaires bénignes à faible débit généralement présentes à la naissance ou peu après. Étant donné la morbidité associée à l'opération, le traitement non opératoire par injection de sclérosant est devenu la norme. Depuis 15 ans, plusieurs patients ayant une malformation lymphatique macrokystique (kyste de plus de 2 cm) qui ont été suivis au centre des chercheurs ont vu leurs lésions disparaître d'elles-mêmes pendant l'attente d'un traitement. Dans la présente étude, les chercheurs analysent les caractéristiques de ces patients qui sont susceptibles de contribuer à cette résolution spontanée. MÉTHODOLOGIE: Les chercheurs ont réalisé une analyse rétrospective des dossiers de la base de données de la clinique des anomalies vasculaires (1999-2014) afin d'en extraire toutes les malformations lymphatiques macrokystiques et ils ont examiné les caractéristiques des patients chez qui la malformation s'était résolue spontanément. RÉSULTATS: Chez les 61 patients présentant une malformation lymphatique macrokystique, sept cas se sont résolus spontanément (11,5 %; quatre filles, trois garçons). Ces derniers avaient un âge médian de deux ans (plage de 0 à 6,5 ans) à l'apparition de la malformation, et un âge médian de quatre ans (plage de dix mois à sept ans) à la résolution. La période médiane entre l'apparition et la résolution s'élevait à 24 mois (plage de trois à 43 mois), et la durée de suivi médian, à quatre ans (plage de un à 15 ans). Tous les cas, sauf un, s'associaient à une infection locale ou à une infection des voies respiratoires supérieures qui avait précédé la résolution. Six des sept lésions se situaient au niveau du cou. CONCLUSION: Parmi les cas étudiés, on constatait la présence d'une infection des voies respiratoires supérieures ou d'une infection locale avant la résolution spontanée de la lésion. Par rapport aux données contenues dans les publications, la proportion de malformations observées après la naissance et de malformations présentes dans la région du cou était plus élevée que dans les autres études. Même si les effets secondaires associés au traitement sont généralement légers ou rares, les populations pédiatriques courent tout de même des risques liés à la sclérothérapie et à l'anesthésie générale connexe. Puisqu'une période médiane de 24 mois s'écoulait entre l'apparition de la lésion et sa résolution, il peut être raisonnable d'observer ces malformations jusqu'à 24 mois avant le traitement si la lésion ne nuit pas à la fonction et ne défigure pas l'enfant de manière considérablement, particulièrement si elle se forme après la naissance ou si elle est située dans la région du cou.