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1.
Langmuir ; 40(10): 5106-5120, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427698

RESUMO

The present study focuses on exploring the physical properties of lipid membranes based on the polyhydroxy oxanorbornane (PH-ONB) headgroup, designed as synthetic analogues of naturally occurring archaeal lipid membranes. Specifically, we study two variants of PH-ONB headgroup-based lipids differing in the number of hydroxy groups present in the headgroup, with one having two hydroxy groups (ONB-2OH) and the other having three (ONB-3OH). These lipids form stable bilayer membranes. The study begins with a comprehensive analysis of the fluorescence characteristics of nitrobenzoxadiazole (NBD)-tagged ONB-based lipids in different solvent environments and within a model lipid membrane 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Subsequently, the physical properties of the ONB-based membranes were examined by using an NBD-tagged ONB-based probe and a commonly used extrinsic 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probe. The steady-state and time-resolved fluorescence properties of the NBD-tagged ONB-based probe and DPH were used to compare the physical properties of the ONB-based membranes, including polarity, fluidity, phase transition, order, hydration, location, heterogeneity, and rotational diffusion. The solid gel to liquid crystalline phase transition temperatures of ONB-2OH and ONB-3OH lipid membranes are found to be (68 ± 1) °C and (74 ± 1) °C, respectively. The variation in organization (size), fluidity, and phase transition temperature of ONB-based lipid membranes is explained by the extent of hydrogen bonding interactions between lipid head groups. ONB-based membranes exhibit characteristics similar to those of phospholipid membranes and possess a notably high phase transition temperature. These properties make them a promising and cost-effective synthetic alternative to archaeal lipid membranes with a wide range of potential applications.


Assuntos
Corantes Fluorescentes , Fosfolipídeos , Corantes Fluorescentes/química , Fosfolipídeos/química , Fenômenos Químicos , Temperatura , Transição de Fase , Bicamadas Lipídicas/química , Fosfatidilcolinas/química
2.
Med Biol Eng Comput ; 60(2): 511-530, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35020123

RESUMO

The detection of inimitable patterns (motif) occurring in a set of biological sequences could elevate new biological discoveries. Its application in recognition of transcription factors and their binding sites have demonstrated the necessity to attain knowledge of gene function, human diseases, and drug design. The literature identifies (ℓ, d) motif search as the widely studied problem in PMS (Planted Motif Search). This paper proposes an efficient optimization algorithm named "Freezing FireFly (FFF)" to solve (ℓ, d) motif search problem. The new strategy freezing such as local and global was added to increase the performance of the basic Firefly algorithm. It freezes the best possible out coming positions even in the lesser brighter one. The performance of the proposed algorithm is experienced on simulated and real datasets. The experimental results show that the proposed algorithm resolves the instance (50, 21) within 1.47 min in the simulated dataset. For real (such as ChIP-seq (Chromatin Immunoprecipitation)) and synthetic datasets, the proposed algorithm runs much faster in comparison to existing state-of-the-art optimization algorithms, including Samselect, TraverStringRef, PMS8, qPMS9, AlignACE, FMGA, and GSGA.


Assuntos
Algoritmos , Humanos , Sítios de Ligação , Biologia Computacional , Congelamento
3.
BJOG ; 129(4): 572-579, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34536318

RESUMO

OBJECTIVES: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery. DESIGN: Cross-sectional analysis. SETTING: United States, 2015-18. POPULATION: Singleton births (20-44 weeks of gestation). EXPOSURE: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation. MAIN OUTCOMES AND MEASURES: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. RESULTS: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00-2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84-90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable. CONCLUSIONS: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates. TWEETABLE ABSTRACT: Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth.


Assuntos
Parto Obstétrico/estatística & dados numéricos , Hipertensão/epidemiologia , Morte Perinatal , Complicações Cardiovasculares na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adolescente , Adulto , Causalidade , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
4.
BJOG ; 129(4): 619-626, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34529344

RESUMO

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.


Assuntos
Frutosamina/sangue , Natimorto/epidemiologia , Adulto , Estudos de Casos e Controles , Causalidade , Feminino , Humanos , Nascido Vivo/epidemiologia , Gravidez , Curva ROC , Fatores de Risco , Estados Unidos/epidemiologia
5.
Structure ; 30(3): 360-370.e6, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-34875216

RESUMO

SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane proteins called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Here, we determine the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64°, and a transmembrane C-terminal helix with an angle of 32°. A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its activating effect on SERCA.


Assuntos
Proteínas de Ligação ao Cálcio , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/metabolismo , Bicamadas Lipídicas/metabolismo , Simulação de Dinâmica Molecular , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/química , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
6.
Elife ; 102021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33978571

RESUMO

Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca2+-transport response to ß-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca2+ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN's cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme's active site, augmenting Ca2+ transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally modified bitopic membrane proteins.


Assuntos
Regulação Alostérica , Proteínas de Ligação ao Cálcio/química , Fosforilação , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/química , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Escherichia coli , Espectroscopia de Ressonância Magnética , Proteínas de Membrana/metabolismo , Estrutura Molecular , Conformação Proteica , Coelhos , Retículo Sarcoplasmático , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transdução de Sinais
7.
BJOG ; 128(2): 252-258, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946651

RESUMO

OBJECTIVE: Approximately 10% of stillbirths are attributed to fetal anomalies, but anomalies are also common in live births. We aimed to assess the relationship between anomalies, by system and stillbirth. DESIGN: Secondary analysis of a prospective, case-control study. SETTING: Multicentre, 59 hospitals in five regional catchment areas in the USA. POPULATION OR SAMPLE: All stillbirths and representative live birth controls. METHODS: Standardised postmortem examinations performed in stillbirths, medical record abstraction for stillbirths and live births. MAIN OUTCOME MEASURES: Incidence of major anomalies, by type, compared between stillbirths and live births with univariable and multivariable analyses using weighted analysis to account for study design and differential consent. RESULTS: Of 465 singleton stillbirths included, 23.4% had one or more major anomalies compared with 4.3% of 1871 live births. Having an anomaly increased the odds of stillbirth; an increasing number of anomalies was more highly associated with stillbirth. Regardless of organ system affected, the presence of an anomaly increased the odds of stillbirth. These relationships remained significant if stillbirths with known genetic abnormalities were excluded. After multivariable analyses, the adjusted odds ratio (aOR) of stillbirth for any anomaly was 4.33 (95% CI 2.80-6.70) and the systems most strongly associated with stillbirth were cystic hygroma (aOR 29.97, 95% CI 5.85-153.57), and thoracic (aOR16.18, 95% CI 4.30-60.94) and craniofacial (aOR 35.25, 95% CI 9.22-134.68) systems. CONCLUSIONS: In pregnancies affected by anomalies, the odds of stillbirth are higher with increasing numbers of anomalies. Anomalies of nearly any organ system increased the odds of stillbirth even when adjusting for gestational age and maternal race. TWEETABLE ABSTRACT: Stillbirth risk increases with anomalies of nearly any organ system and with number of anomalies seen.


Assuntos
Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/patologia , Doenças Fetais/epidemiologia , Doenças Fetais/patologia , Natimorto/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Nascido Vivo , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco
8.
Data Brief ; 31: 105768, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32551344

RESUMO

The Nadergul granodiorite (NG), is a part of Hyderabad Granite Batholith (HGB), exposed at ground level covering an area of 6 km2. Field observational data suggests that the NG is involved in the magma mixing mingling process. Petrographical data shows holocrystaline, phaneritic, coarse grained, inequigranular, mesocratic characteristics, essentially consists of quartz, orthoclase, plagioclase and microcline. The common accessory minerals are hornblende, biotite, clinopyroxene, zircon, fluorite, apatite and opaque. The myrmekitic texture is the most common intergrowth texture which seems to be magmatic origin. Geochemical data suggest that the NG is metaluminous and show calc-alkaline trend. It is charecterised by SiO2 content ranging from 63.55 % to 64.54%, moderate alkali content (Na2O + K2O = 5.6%), relatively high MgO content ranging from 2.8 % to 3.5 %. The total CaO-Na2O-K2O content ranges from 9.5 % to10.4 %. The normalised REE patterns show LREEs enrichment with slight negative europium anomaly. The High Field Strength Elements such as Zr (67.3 to 114.3 ppm), Y (21.1 to 30.1 ppm), Nb (6.3 to 8.5 ppm) and Th (8.4 to 13.8 ppm) are relatively enriched. The granodiorite is I type, falls in the Volcanic Arc Granitoid (VAG) field in tectonic discrimination diagram.

9.
Intensive Care Med ; 45(9): 1177-1189, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31346678

RESUMO

PURPOSE: To provide an update about the rapidly developing changes in the critical care management of acute ischaemic stroke patients. METHODS: A narrative review was conducted in five general areas of acute ischaemic stroke management: reperfusion strategies, anesthesia for endovascular thrombectomy, intensive care unit management, intracranial complications, and ethical considerations. RESULTS: The introduction of effective reperfusion strategies, including IV thrombolysis and endovascular thrombectomy, has revolutionized the management of acute ischaemic stroke and transformed outcomes for patients. Acute therapeutic efforts are targeted to restoring blood flow to the ischaemic penumbra before irreversible tissue injury has occurred. To optimize patient outcomes, secondary insults, such as hypotension, hyperthermia, or hyperglycaemia, that can extend the penumbral area must also be prevented or corrected. The ICU management of acute ischaemic stroke patients, therefore, focuses on the optimization of systemic physiological homeostasis, management of intracranial complications, and neurological and haemodynamic monitoring after reperfusion therapies. Meticulous blood pressure management is of central importance in improving outcomes, particularly in patients that have undergone reperfusion therapies. CONCLUSIONS: While consensus guidelines are available to guide clinical decision making after acute ischaemic stroke, there is limited high-quality evidence for many of the recommended interventions. However, a bundle of medical, endovascular, and surgical strategies, when applied in a timely and consistent manner, can improve long-term stroke outcomes.


Assuntos
Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/fisiopatologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/tendências , Humanos , Medicina Interna/métodos , Medicina Interna/tendências , Reperfusão/efeitos adversos , Reperfusão/métodos , Reperfusão/tendências , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Terapia Trombolítica/tendências , Resultado do Tratamento
10.
BJOG ; 126(10): 1223-1230, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31100201

RESUMO

OBJECTIVE: This study utilized the Dr. Foster Global Comparators database to identify pregnancy complications and associated risk factors that led to severe maternal morbidity during delivery hospitalisations in large university hospitals based in the USA, Australia, and England. DESIGN: Retrospective cohort. SETTING: Births in the USA, England and Australia from 2008 to 2013. SAMPLE: Data from delivery hospitalisations between 2008 and 2013 were examined using the Dr. Foster Global Comparators database. METHODS: We identified delivery hospitalisations with life-threatening diagnoses or use of life-saving procedures, using algorithms for severe maternal morbidity from the Center for Disease Control. Frequency of severe maternal morbidity was calculated for each country. MAIN OUTCOME MEASURES: Multivariable analysis was used to examine the association between morbidity and socio-demographic and clinical characteristics within each country. Chi-square tests assessed differences in covariates between countries. RESULTS: From 2008 to 2013, there were 516 781 deliveries from a total of 18 hospitals: 24.5% from the USA, 57.0% from England and 18.4% from Australia. Overall severe maternal morbidity rate was 8.2 per 1000 deliveries: 15.6 in the USA, 5.0 in England, and 8.2 in Australia. The most common codes identifying severe morbidity included transfusion, disseminated intravascular coagulation, acute renal failure, cardiac events/procedures, ventilation, hysterectomy, and eclampsia. Advanced maternal age, hypertension, diabetes, and substance abuse were associated with severe maternal morbidity in all three countries. CONCLUSION: Rates of severe maternal morbidity differed by country. Identification of geographical, socio-demographic, and clinical differences can help target modifications of practice and potentially reduce severe maternal morbidity. TWEETABLE ABSTRACT: Rates of severe maternal morbidity vary, but risk factors associated with adverse outcomes are similar in developed countries.


Assuntos
Hospitalização/estatística & dados numéricos , Morte Materna/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Austrália/epidemiologia , Centers for Disease Control and Prevention, U.S. , Comorbidade , Bases de Dados Factuais , Inglaterra/epidemiologia , Feminino , Humanos , Idade Materna , Pessoa de Meia-Idade , Complicações do Trabalho de Parto/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
12.
Data Brief ; 21: 1909-1917, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30519616

RESUMO

The data presented in this article are related to research to the research article entitled 'Petrology and Geochemistry Data of the Precambrian granitoids from the Hyderabad part of Eastern Dharwar Craton, Telangana state, India'. The granitoids from the Hyderabad area of the Telangana State are confined to the Precambrian gneissic complex of the northern-eastern part of Eastern Dharwar Craton. They cover 7760 Sq. km of the study area and fall between latitudes 16° 52'-17°42' N and between East longitudes 77° 21'-77° 51' E. The granitoids are mainly classified into grey and pink granites, granodiorites and aplites. The field studies are understood they occasionally contain older mafic enclaves in the form of lensoid bodies and thin bands and cut by younger dolerite dykes, pegmatite and quartz veins and laboratory investigations resolved the classification of the granitods and their chemical histories.

13.
Br J Anaesth ; 121(4): 768-775, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30236239

RESUMO

BACKGROUND: A modified Delphi approach was used to identify a consensus on practical recommendations for the use of non-pharmacological targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke with non-infectious fever (assumed neurogenic fever). METHODS: Nine experts in the management of neurogenic fever participated in the process, involving the completion of online questionnaires, face-to-face discussions, and summary reviews, to consolidate a consensus on targeted temperature management. RESULTS: The panel's recommendations are based on a balance of existing evidence and practical considerations. With this in mind, they highlight the importance of managing neurogenic fever using a single protocol for targeted temperature management. Targeted temperature management should be initiated if the patient temperature increases above 37.5°C, once an appropriate workup for infection has been undertaken. This helps prevent prophylactic targeted temperature management use and ensures infection is addressed appropriately. When neurogenic fever is detected, targeted temperature management should be initiated rapidly if antipyretic agents fail to control the temperature within 1 h, and should then be maintained for as long as there is potential for secondary brain damage. The recommended target temperature for targeted temperature management is 36.5-37.5°C. The use of advanced targeted temperature management methods that enable continuous, or near continuous, temperature measurement and precise temperature control is recommended. CONCLUSIONS: Given the limited heterogeneous evidence currently available on targeted temperature management use in patients with neurogenic fever and intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke, a Delphi approach was appropriate to gather an expert consensus. To aid in the development of future investigations, the panel provides recommendations for data gathering.


Assuntos
Isquemia Encefálica/terapia , Hemorragia Cerebral/terapia , Hipotermia Induzida/métodos , Acidente Vascular Cerebral/terapia , Hemorragia Subaracnóidea/terapia , Antipiréticos/uso terapêutico , Isquemia Encefálica/complicações , Hemorragia Cerebral/complicações , Consenso , Técnica Delphi , Febre/etiologia , Febre/terapia , Humanos , Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/complicações , Inquéritos e Questionários , Reino Unido
14.
Am J Perinatol ; 35(7): 660-668, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29212131

RESUMO

OBJECTIVE: We sought to develop a model to calculate the likelihood of vaginal delivery in nulliparous women undergoing induction at term. STUDY DESIGN: We obtained data from the Consortium on Safe Labor by including nulliparous women with term singleton pregnancies undergoing induction of labor at term. Women with contraindications for vaginal delivery were excluded. A stepwise logistic regression analysis was used to identify the predictors associated with vaginal delivery by considering maternal characteristics and comorbidities and fetal conditions. The receiver operating characteristic curve, with an area under the curve (AUC) was used to assess the accuracy of the model. RESULTS: Of 10,591 nulliparous women who underwent induction of labor, 8,202 (77.4%) women had vaginal delivery. Our model identified maternal age, gestational age at delivery, race, maternal height, prepregnancy weight, gestational weight gain, cervical exam on admission (dilation, effacement, and station), chronic hypertension, gestational diabetes, pregestational diabetes, and abruption as significant predictors for successful vaginal delivery. The overall predictive ability of the final model, as measured by the AUC was 0.759 (95% confidence interval, 0.749-0.770). CONCLUSION: We identified independent risk factors that can be used to predict vaginal delivery among nulliparas undergoing induction at term. Our predictor provides women with additional information when considering induction.


Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Paridade , Adulto , Feminino , Humanos , Trabalho de Parto Induzido/efeitos adversos , Modelos Logísticos , Nomogramas , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Nascimento a Termo , Falha de Tratamento , Estados Unidos , Adulto Jovem
15.
Ultrasound Obstet Gynecol ; 52(6): 757-762, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29155504

RESUMO

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
17-alfa-Hidroxiprogesterona/uso terapêutico , Líquido Amniótico/química , Colo do Útero/diagnóstico por imagem , Nascimento Prematuro/epidemiologia , Ultrassonografia Pré-Natal/métodos , Adulto , Medida do Comprimento Cervical , Estudos de Coortes , Feminino , Humanos , Idade Materna , Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
16.
BJOG ; 125(3): 343-350, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28139890

RESUMO

OBJECTIVE: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). DESIGN: Case-control. SETTING: Three tertiary-care centres across the USA. POPULATION: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. METHODS: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P). MAIN OUTCOME MEASURES: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction). CONCLUSION: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P. TWEETABLE ABSTRACT: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment.


Assuntos
Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Nascimento Prematuro , Adulto , Análise de Variância , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Farmacogenética , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/genética , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Recidiva , Estados Unidos/epidemiologia , Sequenciamento do Exoma/métodos , Sequenciamento do Exoma/estatística & dados numéricos
17.
BJOG ; 123(11): 1797-803, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26643181

RESUMO

OBJECTIVES: To estimate the incidence and risk of complications associated with a fetal scalp electrode and to determine whether its application in the setting of operative vaginal delivery was associated with increased neonatal morbidity. DESIGN: Retrospective cohort study. SETTING: Twelve clinical centers with 19 hospitals across nine American Congress of Obstetricians and Gynecologists US districts. POPULATION: Women in the USA. METHODS: We evaluated 171 698 women with singleton deliveries ≥ 23 weeks of gestation in a secondary analysis of the Consortium on Safe Labor study between 2002 and 2008, after excluding conditions that precluded fetal scalp electrode application such as prelabour caesarean delivery. Secondary analysis limited to operative vaginal deliveries ≥ 34 weeks of gestation was also performed. MAIN OUTCOME MEASURES: Incidences and adjusted odds ratios with 95% confidence intervals of neonatal complications were calculated, controlling for maternal characteristics, delivery mode and pregnancy complications. RESULTS: Fetal scalp electrode was used in 37 492 (22%) of deliveries. In non-operative vaginal delivery, fetal scalp electrode was associated with increased risk of injury to scalp due to birth trauma (1.2% versus 0.9%; adjusted odds ratios 1.62; 95% confidence intervals 1.41-1.86) and cephalohaematoma (1.0% versus 0.9%; adjusted odds ratios 1.57; 95% confidence intervals 1.36-1.83). Neonatal complications were not significantly different comparing fetal scalp electrode with vacuum-assisted vaginal delivery and vacuum-assisted vaginal delivery alone or comparing fetal scalp electrode with forceps-assisted vaginal delivery and forceps-assisted vaginal delivery alone. CONCLUSIONS: We found increased neonatal morbidity with fetal scalp electrode though the absolute risk was very low. It is possible that these findings reflect an underlying indication for its use. Our findings support the use of fetal scalp electrodes when clinically indicated. TWEETABLE ABSTRACT: Neonatal risks associated with fetal scalp electrode use were low (injury to scalp 1.2% and cephalohaematoma 1.0%).


Assuntos
Traumatismos do Nascimento/etiologia , Cardiotocografia/instrumentação , Parto Obstétrico/efeitos adversos , Eletrodos/efeitos adversos , Couro Cabeludo/lesões , Adulto , Traumatismos do Nascimento/epidemiologia , Cardiotocografia/efeitos adversos , Parto Obstétrico/métodos , Feminino , Humanos , Incidência , Recém-Nascido , Razão de Chances , Gravidez , Estudos Retrospectivos , Couro Cabeludo/embriologia , Estados Unidos/epidemiologia
19.
J Mater Chem B ; 4(48): 8025-8032, 2016 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-32263792

RESUMO

The self-assembly of non-ionic amphiphiles with a hydroxylated oxanorbornane head-group was controlled using amino acid units as spacers between hydrophilic and lipophilic domains to get spherical supramolecular aggregates. The ability of these systems to harbour therapeutic agents like ibuprofen, and their drug-release profiles were evaluated. Apart from directing the assembly, the intervening amino acid unit was found to help in drug entrapment as well. The presence of cholesterol improved their drug-loading ability, and an encapsulation efficiency of up to 66% was shown by the formulation containing the phenylalanine residue as the spacer (NC1c). There was no burst release, and 45% drug release was observed at the end of 24 h in this case (cf. soyaphosphatidylcholine based formulation = 49%). The results from SEM, Cryo-TEM, PXRD and confocal microscopic studies with some insights into molecular packing in this class of aggregates are also included.

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