Abstract Background Antiphospholipid syndrome (APS) is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. Anticardiolipin antibodies (aCL), anti-β2 glycoprotein-I (ab2GPI) ...and lupus anticoagulant (LA) are the main autoantibodies found in APS. Despite the amassed body of clinical knowledge, the risk of obstetric complications associated with specific antibody profile has not been well established. Objective To assess the risk of obstetric complications in women with primary APS associated with specific antibody profile Study design The PREGNANTS study is a multicenter, retrospective, cohort study. Diagnosis and classification of APS were based on the 2006 International revised criteria. All women included in the study had at least one clinical criteria for APS, were positive for at least one antiphospholipid antibodies (aCL, ab2GPI and/or LA), and were treated with low-dose aspirin and prophylactic low molecular weight heparin (LMWH) starting from the first trimester. Only singleton pregnancies with primary APS were included. The primary outcome was livebirth, defined as any delivery of a live infant after 22 weeks. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction (IUGR) and stillbirth. We planned to assess the outcomes associated with the various antibody profile (test result for LA, aCL and ab2GPI). Results There were 750 singleton pregnancies with primary APS in the study cohort. 54 (7.2%) were positive for LA only, 458 (61.0%) for aCL only, 128 (17.1%) for ab2GPI only; while 90 (12.0%) were double positive and LA negative and 20 (2.7%) were triple positive. The incidence of livebirth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared to women with only one antibody positive test results, women with multiple antibody positive results had a significantly lower livebirth (40.9% vs 56.6%; aOR 0.71, 95% CI 0.51 to 0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; aOR 1.56, 95% CI 1.22 to 1.95) and with severe features (22.7% vs 13.8%, aOR 1.66, 95% CI 1.19 to 2.49), IUGR (53.6% vs 40.8%; aOR 2.31, 95% CI 1.17 to 2.61) and stillbirth (36.4% vs 21.7%; aOR 2.67, 95% CI 1.22 to 2.94). In women with only one positive test result, women with ab2GPI positivity present alone had a significantly lower livebirth (47.7% vs 56.3% vs 79.6%; p<0.01), and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; p<0.01) and with severe features (17.2% vs 14.4% vs 0%; p=0.02), IUGR (48.4% vs 40.1% vs 25.9%; p<0.01) and stillbirth (29.7% vs 21.2% vs 7.4%; p<0.01) compared to women with aCL and to women with LA present alone, respectively. In the group of women with more than one antibody positivity, triple-positive women had lower livebirth (30% vs 43.3%; aOR 0.69, 95% CI 0.22 to 0.91), and higher incidence of IUGR (70.0% vs 50.0%; aOR 2.40, 95% CI 1.15 to 2.99) compared to double positive and LA negative women. Conclusion In singleton pregnancies with primary APS, aCL is the most common sole antiphospholipid antibody present, but ab2GPI is the one associated with the lowest livebirth rate and highest incidence of preeclampsia, IUGR, and stillbirth, compared to presence of aCL or LA alone. Primary APS women have an increased risk of obstetric complications and lower livebirth when more than one antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic LMWH, chance of a live-birth neonate is only 30% for triple-positive women.
The burden of depressive disorder is large and new treatment approaches are required. Repurposing widely available drugs such as statins may be a time- and cost-effective solution. Statins have ...anti-inflammatory and anti-oxidant properties which have been shown to be relevant to the pathophysiology of depression. This study assesses the efficacy, acceptability, tolerability, and safety of statins in major depressive disorder.
Our study is an update and extension of a previous meta-analysis published in 2016 by Salagre et al. We performed a systematic review (PubMed/MEDLINE, Cochrane CENTRAL, ISI Web of Science, CINAHL, and ClinicalTrials.gov until the 1st September 2020) and meta-analysis of randomized controlled trials using any statin against placebo or any other statin in the treatment of major depressive disorder. Our primary efficacy outcome measure was the mean value on any standardized scale for depressive symptoms at 8 weeks of treatment. We also calculated outcomes for efficacy, response, and remission at 2, 4, and 12 weeks, as well as acceptability (dropouts for any cause), tolerability (dropouts due to any adverse event), and safety (any adverse event) outcomes at the studies' endpoints. Furthermore, we conducted an exploratory network meta-analysis for the primary efficacy outcome to identify potential differences between statins.
We retrieved five randomized controlled trials meeting our inclusion criteria: four used a statin in addition to an antidepressant and compared it to placebo plus antidepressant, and one compared two statins alone. and one comparing one statin with another. Statins compared to placebo in addition to antidepressants were efficacious at 8 weeks (N = 255, SMD = -0.48, 95% CI = -0.74 to -0. 22) and 12 weeks (N = 134, SMD = -0.47, 95% CI = -0.89 to -0.05, moderate certainty) with no difference for acceptability, tolerability, and safety (low certainty). An exploratory network meta-analysis suggested that the most lipophilic statins, especially simvastatin, could be more efficacious than less lipophilic or hydrophilic molecules.
This systematic review suggests the efficacy, acceptability, tolerability, and safety of statins in addition to antidepressants in patients with major depressive disorder. Further clinical trials in different settings are required to test this result.
PROSPERO registration: CRD42020170938.
Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to ...pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%.
We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis.
A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%).
In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).
Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely ...needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.
We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.
Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.
We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.
Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.
Finding maximal exact matches in graphs Rizzo, Nicola; Cáceres, Manuel; Mäkinen, Veli
Algorithms for molecular biology,
03/2024, Volume:
19, Issue:
1
Journal Article
Peer reviewed
Open access
We study the problem of finding maximal exact matches (MEMs) between a query string Q and a labeled graph G. MEMs are an important class of seeds, often used in seed-chain-extend type of practical ...alignment methods because of their strong connections to classical metrics. A principled way to speed up chaining is to limit the number of MEMs by considering only MEMs of length at least
(
-MEMs). However, on arbitrary input graphs, the problem of finding MEMs cannot be solved in truly sub-quadratic time under SETH (Equi et al., TALG 2023) even on acyclic graphs.
In this paper we show an
-time algorithm finding all
-MEMs between Q and G spanning exactly L nodes in G, where n is the total length of node labels, d is the maximum degree of a node in G,
, and
is the number of output MEMs. We use this algorithm to develop a
-MEM finding solution on indexable Elastic Founder Graphs (Equi et al., Algorithmica 2022) running in time
, where H is the maximum number of nodes in a block, and
is the total number of
-MEMs. Our results generalize to the analysis of multiple query strings (MEMs between G and any of the strings). Additionally, we provide some experimental results showing that the number of graph MEMs is an order of magnitude smaller than the number of string MEMs of the corresponding concatenated collection.
We show that seed-chain-extend type of alignment methods can be implemented on top of indexable Elastic Founder Graphs by providing an efficient way to produce the seeds between a set of queries and the graph. The code is available in https://github.com/algbio/efg-mems .
Objective The objective of the study was to assess the effectiveness of ultrasound in the antenatal prediction of symptomatic congenital cytomegalovirus (CMV) infection. Study Design The sonograms of ...650 fetuses from mothers with primary CMV infection were correlated to fetal or neonatal outcome. Infection status was disclosed by viral urine isolation at birth or CMV tissue inclusions at autopsy. Classification of symptomatic disease was based on postnatal clinical or laboratory findings or macroscopic evidence of tissue damage at autopsy. Results Ultrasound abnormalities were found in 51 of 600 mothers with primary infection (8.5%) and 23 of 154 congenitally infected fetuses (14.9%). Symptomatic congenital infection resulted in 1 of 23 and 68 of 131 cases with or without abnormal sonographic findings, respectively. Positive predictive values of ultrasound vs symptomatic congenital infection was 35.3% relating to all fetuses or infants from mothers with primary infection and 78.3% relating to fetuses or infants with congenital infection. Conclusion When fetal infection status is unknown, ultrasound abnormalities predict symptomatic congenital infection in only a third of cases.
Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in ...the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins' putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins' effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins' antidepressant effects while also improving our understanding of the physiopathological basis of depression.
Background: Psychiatric disorders are large contributors to the global disease burden, but research on the impact of climate change on them is limited. Our aim is to investigate the correlation ...between temperature and exacerbations of psychiatric disorders to help inform clinical management and future public health policies. Methods: Temperature records for the summer months from 2013 to 2022 were obtained from the meteorological station of the Department of Physics of Turin University. Data on patients admitted to the acute psychiatric unit were extracted from registries of San Luigi Gonzaga University Hospital (Turin, Italy). Regression analyses were used to investigate the correlation between temperature and number of admissions and to test for confounding variables. Results: A total of 1600 admissions were recorded. The monthly temperature and number of admissions were directly correlated (p = 0.0020). The correlation was significant for the subgroup of admissions due to Bipolar Disorders (p = 0.0011), but not for schizophrenia or major depressive disorder. After multiple regression analyses, the effect of temperature remained significant (p = 0.0406). Conclusions: These results confirm the impact of meteorological factors on mental disorders, particularly on BD. This can contribute to personalised follow-up and efficient resource allocation and poses grounds for studies into etiopathological mechanisms and therapeutic implications.
Autism spectrum disorders (ASD) and non-affective psychoses such as schizophrenia are commonly acknowledged as discrete entities. Previous research has revealed evidence of high comorbidity between ...these conditions, but their differential diagnosis proves difficult in routine clinical practice due to the similarities between core symptoms of each disorder. The prevalence of comorbid non-affective psychoses in individuals with ASD is uncertain, with studies reporting rates ranging from 0% to 61.5%. We therefore performed a systematic review and pooled analysis of the available studies reporting the prevalence of non-affective psychosis in ASD. Fourteen studies, including a total of 1708 participants, were included, with a weighted pooled prevalence assessed at 9.5% (95% CI 2.6 to 16.0). In view of significant heterogeneity amongst the studies, subgroup analyses were conducted. We observed higher prevalence of non-affective psychoses among ASD inpatients versus outpatients, when operationalised criteria were used, and in studies with smaller sample sizes, whereas the figures were comparable between children and adults with ASD. Our results suggest that future studies involving larger samples should implement both operationalized criteria and specific scales for the assessment of psychotic symptoms in individuals with ASD. A deeper understanding of both differential and comorbid features of ASD and non-affective psychosis will be required for the development of optimized clinical management protocols.
Objective The purpose of this study was to determine whether the combined distribution of a panel of cellular messenger RNA markers can detect preeclampsia long before onset. Study Design We compared ...blood at 10-14 weeks from 11 women who ultimately experienced preeclampsia with 88 matched control subjects. After multiples of the median conversion of all the markers, logistic regression was used to calculate the risk of the development of preeclampsia. Results Higher multiples of the median values than expected were found for endoglin, fms-related tyrosine kinase 1, and transforming growth factor–β1. Lower multiples of the median values were found for placental growth factor and placental protein 13. Endoglin fms-related tyrosine kinase 1 and transforming growth factor–β1 had the best discriminant power. Messenger RNA species provided independent contributions to the prediction of preeclampsia. In fact, 11 women with preeclampsia scored a median risk of 50% of experiencing preeclampsia. Control subjects scored a median risk of preeclampsia of 0.18%. The detection rate at a 5% false positive rate was 72.3%. Conclusion The messenger RNA dosage in maternal blood would be a useful method for the calculation of the risk of the development of preeclampsia.
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