RESUMO
BACKGROUND: Small-for-gestational-age (SGA), commonly caused by poor placentation, is a major contributor to global perinatal mortality and morbidity. Maternal serum levels of placental protein and angiogenic factors are changed in SGA. Using data from a population-based pregnancy cohort, we estimated the relationships between levels of second-trimester pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and serum soluble fms-like tyrosine kinase-1 (sFlt-1) with SGA. METHODS: Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80â. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24-28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders. RESULTS: The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613-1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679-1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18-3.24) compared to AGA pregnancies (1.77, IQR 1.06-2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09-1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21-1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12-1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70-0.92; p = 0.002, and aRR 0.86, 95% CI 0.75-0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02-1.36; p = 0.025). CONCLUSIONS: This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA.
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Biomarcadores , Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Placentário , Insuficiência Placentária , Segundo Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Humanos , Feminino , Gravidez , Fator de Crescimento Placentário/sangue , Biomarcadores/sangue , Estudos Prospectivos , Adulto , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Proteína Plasmática A Associada à Gravidez/análise , Proteína Plasmática A Associada à Gravidez/metabolismo , Insuficiência Placentária/sangue , Recém-Nascido , Segundo Trimestre da Gravidez/sangue , Bangladesh/epidemiologia , Adulto Jovem , Idade Gestacional , Fatores de RiscoRESUMO
BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.
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Resultado da Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Nascimento Prematuro/epidemiologia , Hemoglobinas Glicadas , Cesárea , Países em Desenvolvimento , Bangladesh , Paquistão , TanzâniaRESUMO
BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes. METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group. RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes. CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.
Assuntos
Hipertensão Induzida pela Gravidez , Guias de Prática Clínica como Assunto , Nascimento Prematuro , Natimorto , Humanos , Feminino , Gravidez , Nascimento Prematuro/epidemiologia , Natimorto/epidemiologia , Adulto , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Estados Unidos/epidemiologia , Paquistão/epidemiologia , Estudos de Coortes , American Heart Association , Bangladesh/epidemiologia , Tanzânia/epidemiologia , Adulto Jovem , Pressão Sanguínea , Recém-Nascido , Ásia MeridionalRESUMO
Approximately 2.2% of Libyans have chronic hepatitis B (CHB) and are at the highest risk of developing end-stage disease complications. Several resource-limited countries, including Libya, may be far from achieving the WHO goal of hepatitis B elimination by 2030 as a result of several testing and linkage to care (LTC) barriers. In Libya, data about the current HBV infection situation is scarce. Therefore, our study aimed to evaluate the trends of HBV in eastern Libya, Tobruk region, and try to identify the region-specific gaps and barriers that could potentially delay the WHO goal of HBV elimination. An eighteen-year retrospective review of records of the main district medical center in the region was done to estimate the trends of HBV infection and qualitative interviews with the clinical staff of the CHB registry in the region were conducted to investigate the current status of HBV management. Out of 392,952 records, 371 (0.09%) HBV-positive were recorded and declining trends of the infection were noticed over the study period. Until late 2019, there was no linkage to care or follow-up for people with HBV infection. However, a CHB registry was established in late 2019 to manage HBV infections in the region, yet there are several barriers such as the lack of diagnostic infrastructure for liver function assessment and antiviral treatment. Despite the significant decline observed in the occurrence of HBV infection and introduction of important HBV management steps such as establishment of the CHB registry, there are still several barriers that could delay the elimination of the infection.
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Hepatite B Crônica , Humanos , Líbia/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/terapia , Adulto Jovem , Adolescente , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Erradicação de Doenças/organização & administração , Vírus da Hepatite B , Acessibilidade aos Serviços de SaúdeRESUMO
Acute Toxoplasma gondii infections can influence the liver as well as other organs. Many cytokines and proteins play a role in the acute response against infection. Tumor necrosis factor alpha (TNF alpha) is a cytokine that plays a key function in stimulating hepatocytes to produce acute phase proteins. In this study, we investigated TNF alpha levels associated with the levels of macroglobulin, haptoglobin, hemopexin, C-reactive protein (CRP), albumin, serum amyloid alpha protein (SAA), and clusterin, which are acute phase proteins, in serum of mice with T. gondii infection. In the experiment, a total of 24 mice were used; 6 mice constituted the control group and 18 mice were infected with the RH strain. On the 2nd, 4th, and 6th days following the infection, 6 animals were euthanized, and their serums were collected. Compared to the control group, we observed a statistically significant decrease in albumin concentration in the group with T. gondii infection on the 6th day. Also, this group displayed a statistically significant, gradual increase in clusterin levels on the 2nd and 6th days, C-reactive protein levels on the 4th day, haptoglobin levels on the 2nd and 4th days, hemopexin levels on the 2nd day, serum amyloid A levels on the 2nd, 4th, and 6th days, and TNF-α levels on the 2nd, 4th, and 6th days (p < 0.05). TNF-α was strongly positively correlated with CRP, SAA, and clusterin, moderately positively correlated with hemopexin, and strongly negatively correlated with albumin. The increase in CRP, SAA, clusterin, and hemopexin levels on the 2nd day after infection, in parallel with the increase in TNF-α levels, indicates that these proteins can be considered as major acute phase proteins in acute T. gondii infection in mice. The data obtained here may be helpful for the diagnosis of T. gondii infection and for monitoring treatments.
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Toxoplasma , Toxoplasmose Animal , Toxoplasmose , Proteínas de Fase Aguda , Animais , Proteína C-Reativa , Clusterina , Citocinas/metabolismo , Haptoglobinas , Hemopexina , Camundongos , Toxoplasmose/patologia , Toxoplasmose Animal/patologia , Fator de Necrose Tumoral alfaRESUMO
Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS-13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS-13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl-xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post-infection. Results of the study revealed that the levels of ADAMTS-13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl-xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post-infection ADAMTS-13 increased significantly and this may play an important role in the regulation and protection of the blood-brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii-mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS-13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of T. gondii-infected mice.
Assuntos
Proteína ADAMTS13/metabolismo , Apoptose , Encéfalo/enzimologia , Encefalite Infecciosa/enzimologia , Toxoplasmose Cerebral/enzimologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Feminino , Encefalite Infecciosa/parasitologia , Encefalite Infecciosa/patologia , Encefalite Infecciosa/fisiopatologia , Camundongos , Toxoplasmose Cerebral/patologia , Toxoplasmose Cerebral/fisiopatologiaRESUMO
Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation. Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats. Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later. Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage. Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.
Assuntos
Acetaminofen , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Nigella sativa , Extratos Vegetais/farmacologia , Acetilcisteína/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Creatinina/sangue , Citoproteção , Modelos Animais de Doenças , Etanol/química , Feminino , Glutationa/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/patologia , Malondialdeído/metabolismo , Nigella sativa/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Sementes , Solventes/química , Superóxido Dismutase/metabolismo , Ureia/sangueRESUMO
Toxoplasma gondii is an intracellular parasite with the potential of causing severe encephalitis among immunocompromised human and animals. The aim of this experimental study was to investigate the immunomodulatory and immunopathological role of nitric oxide (NO) in central nervous systems and to identify any correlation between toxoplasmosis neuropathology and investigate the consequences of the cellular responses protect against T. gondii. Mice were infected with ME49 strain T. gondii and levels of endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS), glial fibrillary acidic protein (GFAP) and neurofilament (NF) were examined in brain tissues by immunohistochemistry, during the development and establishment of a chronic infection at 10 30 and 60 days post infection. Results of the study revealed that the levels of eNOS (p < 0.05), nNOS (p < 0.05), iNOS (p < 0.005), GFAP (p < 0.005) and NF (p < 0.005) were remarkably higher in T. gondii-infected mice than in uninfected control. The most prominent finding from our study was 10 and 30 days after inoculation data indicating that increased levels of NO not only a potential neuroprotective role for immunoregulatory and immunopathological but also might be a molecular trigger of bradyzoite development. Furthermore, this findings were shown that high expressed NO origin was not only inducible nitric oxide synthase but also endothelial and neuronal. We demonstrated that activation of astrocytes and microglia/macrophages is a significant event in toxoplasma encephalitis (TE). The results also clearly indicated that increased levels of NO might contribute to neuropathology related with TE. Furthermore, expression of NF might gives an idea of the progress and critical for diagnostic significance of this disease.
Assuntos
Encefalite/metabolismo , Óxido Nítrico/metabolismo , Toxoplasmose Cerebral/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Encéfalo/parasitologia , Encefalite/parasitologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Filamentos Intermediários/metabolismo , Camundongos , Óxido Nítrico Sintase/metabolismoRESUMO
Background: Preterm birth (PTB) and its complications are important public health problems. Its aetiology is multifactorial and involves both modifiable and non-modifiable factors. Among the modifiable risk factors, micronutrient deficiencies, including maternal folate deficiency, are increasingly being studied in PTB. In this study, we estimated the prevalence of folate deficiency during pregnancy and examined its association with PTB among rural Bangladeshi women. Methods: We conducted a nested case-control study using data from a population-based cohort of 3000 pregnant women who were enrolled between 8 and 19 weeks of gestation following ultrasound confirmation of gestational age. Sociodemographic, epidemiologic, clinical, and pregnancy outcomes data were collected through home visits, while blood samples were collected at enrolment and 24-28 weeks of gestation during pregnancy. We included all women who delivered preterm (defined as live births <37 weeks of gestation) as cases (n = 235) and a random sample of women having a term birth as controls (n = 658). The main exposure was folate concentrations in maternal serum during 24-28 weeks of pregnancy. We categorised women into folate deficient (<3 ng/mL) and not deficient (≥3 ng/mL). We then performed multivariable logistic regression analysis to examine the association between maternal folate levels and PTB, adjusting for relevant covariates. Results: Thirty-eight per cent of the enrolled pregnant women were folate deficient. Maternal serum folate deficiency was significantly associated with PTB (adjusted OR (aOR) = 1.73; 95% confidence interval (CI) = 1.27-2.36). The risk of PTB was also higher among women who were of short stature (aOR = 1.83; 95% CI = 1.27-2.63), primiparous (aOR = 1.60; 95% CI = 1.15-2.22), and had exposure to passive smoking (aOR = 1.54; 95% CI = 1.02-2.31). Conclusions: The prevalence of folate deficiency was high among pregnant women in rural Bangladesh, and folate deficiency was significantly associated with an increased risk of preterm birth.
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Deficiência de Ácido Fólico , Nascimento Prematuro , Humanos , Feminino , Gravidez , Estudos de Casos e Controles , Nascimento Prematuro/epidemiologia , Adulto , Deficiência de Ácido Fólico/epidemiologia , Bangladesh/epidemiologia , Fatores de Risco , Adulto Jovem , Complicações na Gravidez/epidemiologia , Prevalência , Ácido Fólico/sangue , População Rural/estatística & dados numéricosRESUMO
BACKGROUND: Ileal pouch anal anastomosis (IPAA) is the treatment of choice for chronic, medically refractory mucosal ulcerative colitis, indeterminate colitis, familial adenomatous polyposis (FAP), and a select group of patients with Crohn's disease. AIM: : We report outcomes, complications, and quality of life (QOL) in a cohort of 3707 patients treated at our institution from January 1984 to March 2010. METHODS: Data were collected from a prospectively maintained database and chart review of 3707 consecutive primary IPAA cases. Patient demographics, postoperative complications, functional outcomes, and QOL data were available. Follow-up consisted of clinical examination with assessment of pouch function and QOL. RESULTS: A total of 3707 patients underwent primary pouch and 328 underwent redo pouch surgery. Postoperative histopathological diagnoses were mucosal ulcerative colitis (n = 2953, 79.7%), indeterminate colitis (n = 63, 1.7%), FAP (n = 223, 6%), Crohn's disease (n = 150, 4%), cancer/dysplasia (n = 97, 2.6%), and others (n = 221, 6.0%). Early perioperative complications were encountered in 33.5% of patients with a mortality rate of 0.1%. Excluding pouchitis, late complications were experienced by 29.1% of patients. Of those patients who had IPAA at our institution, pouch failure occurred in 197 patients (5.3%). During a median follow-up of 84 months, 119 patients (3.2%) required excision of the pouch, 32 (0.8%) had a nonfunctioning pouch, and 46 patients (1.2%) had redo IPAA. Functional outcomes and QOL were good or excellent in 95% of patients and similar in each histopathological subgroup. CONCLUSIONS: IPAA is an excellent option for patients with MUC, IC, FAP, and select patients with Crohn's disease.
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Bolsas Cólicas , Complicações Pós-Operatórias , Qualidade de Vida , Polipose Adenomatosa do Colo/cirurgia , Adulto , Canal Anal/cirurgia , Anastomose Cirúrgica , Colite/cirurgia , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Doença de Crohn/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.
RESUMO
Cystic echinococcosis is a zoonotic parasitic disease caused by Echinococcus granulosus. The main hosts in the life cycle of this parasite are dogs and other carnivores; The intermediate hosts are human, sheep, goat, cattle, pig, buffalo, horse and camel. The parasite damages the tissue by forming lesions in the form of fluid-filled cysts in the liver. These lesions are bounded by a layer of local inflammatory cells formed by the host. In the layer formed by this inflammatory response, there are lymphocytes, neutrophils and eosinophil leukocytes, including macrophages. Samples taken from sheep with hydatid cysts in their livers were followed for pathological analysis, and then histopathological and immunohistochemical examinations were performed. After histopathological examinations, the types of macrophages involved in the local immune response against cysts in the liver were determined by immunohistochemical methods using anti-INOS and anti-IL-10 antibodies. INOS and IL-10 immunopositivity were detected in all samples. Statistically, no significant difference was observed between these immunopositivity. This showed that both macrophage types are involved in the local immune response to hydatid cyst, and that Th1 and Th2 immune response stimulation continues together. It was concluded that in future studies that will be planned and experimentally, it will be possible to reveal more clearly how these macrophage types take part in the local immune response.
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Equinococose , Echinococcus granulosus , Doenças dos Ovinos , Animais , Equinococose/imunologia , Equinococose/parasitologia , Equinococose/veterinária , Imunidade , Fígado/parasitologia , Macrófagos , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologiaRESUMO
Background: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh. Methods: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models. Results: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16, 95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years. Conclusions: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.
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COVID-19 , Anticorpos Antivirais , Bangladesh/epidemiologia , COVID-19/epidemiologia , Criança , Estudos de Coortes , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC-MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value.
Assuntos
Metabolômica , Ultrassonografia Pré-Natal , Cromatografia Líquida , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , GravidezRESUMO
AIM: Evidence is lacking whether an abscess associated with anastomotic leak after an ileal pouch-anal anastomosis (IPAA) should be drained by transanal or CT-guided drainage. Therefore, the aim of this study was to compare outcomes after the two techniques for drainage. METHOD: Patients who underwent IPAA (1984-2009) and diagnosed with a pelvic abscess associated with an anastomotic leak were identified. The choice of operative or image-guided drainage was based on surgeon preference. Differences between patients undergoing transanal (group TA) and CT-guided drainage (group CT) were determined. RESULTS: Groups TA (n = 53) and CT (n = 18) had similar age (p = 0.3), gender (p = 0.3), body mass index (p = 0.6), steroid use (p = 0.4), albumin level (p = 0.9), ileostomy (p = 0.6), and follow-up time (p = 0.5). The size of the abscess was greater in group CT (p = 0.012). Two patients developed fistula at the CT-guided drainage site. Both healed after conservative treatment and drainage of associated gluteal abscess, respectively. Thirteen patients in group TA and three patients in group CT (p = 0.6) had failure of drainage and underwent surgery. The success rates for the procedures in terms of long-term pouch retention were 75.5% and 83%, respectively, for TA and CT. Groups TA and CT had similar bowel frequency (p = 0.9), incontinence (p = 0.6), urgency (p = 0.9), seepage (p = 0.6), pad usage (p = 0.1), quality of life (p = 0.9), and happiness with surgery (p = 0.9). CONCLUSIONS: There is a risk of fistula at drainage site after a CT-guided drainage of the pelvic abscess associated with anastomotic leak following IPAA. Transanal and CT-guided drainage are equally effective and result in similar long-term pouch-related outcomes.
Assuntos
Abscesso/etiologia , Canal Anal/cirurgia , Fístula Anastomótica/etiologia , Bolsas Cólicas/efeitos adversos , Drenagem/métodos , Pelve/patologia , Tomografia Computadorizada por Raios X , Abscesso/diagnóstico por imagem , Adulto , Canal Anal/diagnóstico por imagem , Anastomose Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Pelve/diagnóstico por imagem , Qualidade de Vida , Falha de Tratamento , Resultado do TratamentoRESUMO
To discover lipidomic alterations during pregnancy in mothers who subsequently delivered small for gestational age (SGA) neonates and identify predictive lipid markers that can help recognize and manage these mothers, we carried out untargeted lipidomics on maternal serum samples collected between 24-28 weeks of gestation. We used a nested case-control study design and serum from mothers who delivered SGA and appropriate for gestational age babies. We applied untargeted lipidomics using mass spectrometry to characterize lipids and discover changes associated with SGA births during pregnancy. Multivariate pattern recognition software Collaborative Laboratory Integrated Reports (CLIR) was used for the post-analytical recognition of range differences in lipid ratios that could differentiate between SGA and control mothers and their integration for complete separation between the two groups. Here, we report changes in lipids from serum collected during pregnancy in mothers who delivered SGA neonates. In contrast to normal pregnancies where lysophosphatidic acid increased over the course of the pregnancy owing to increased activity of lysophospholipase D, we observed a decrease (32%; P = 0.05) of 20:4-lysophosphatidic acid in SGA mothers, which could potentially compromise fetal growth and development. Integration of lipid ratios in an interpretive tool (CLIR) could completely separate SGA mothers from controls demonstrating the power of untargeted lipidomic analyses for identifying novel predictive biomarkers. Additional studies are required for further assessment of the lipid biomarkers identified in this report.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Lipidômica , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Lisofosfolipídeos , GravidezRESUMO
Self-regulation (or so-called homeostasis) is a property of all living organisms to maintain an internal stable state through specialized biofeedback mechanisms under varying external and internal conditions. Although these feedback mechanisms in living organisms are complex networks and hard to implement one-to-one in artificial systems, the new approaches in soft robotics may benefit from the concept of self-regulation-especially in the new endeavors of making untethered, autonomous soft robots. In this study, we show a simple system, in which plant robots display heliotropism (sun tracking) and nyctinasty (leaf opening) through artificial self-regulation attained through a bioinspired transpiration mechanism. The feedback involves dehydration/hydration and transpiration events that keep the stem continuously in a metastable position, which maximizes light on plant leaves and the efficiency of light harvesting when solar panels are attached on leaves. We also demonstrate that this artificial feedback can be regulated by doping with light-absorbing chemicals or by changing the geometry of the system, and it can further be expanded to other lightweight systems. Implementing self-regulation into (soft) robots through bioinspired material feedback is beneficial not only for energy efficiency and harvesting but also for achieving embodied intelligence in autonomous soft robots.
Assuntos
Materiais Biomiméticos , Robótica , Materiais Biomiméticos/química , Fototropismo , Folhas de Planta , Luz SolarRESUMO
Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.
Assuntos
Perfilação da Expressão Gênica/métodos , Metabolômica/métodos , Assistência Perinatal , Gravidez , Nascimento Prematuro , Melhoria de Qualidade/organização & administração , Adulto , Causalidade , Regras de Decisão Clínica , Países em Desenvolvimento , Diagnóstico Precoce , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Aprendizado de Máquina , Assistência Perinatal/métodos , Assistência Perinatal/normas , Mortalidade Perinatal , Gravidez/sangue , Gravidez/urina , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controleRESUMO
The neurotropic pathogen Toxoplasma gondii infects about one-third of the human population. Both acute and chronic (latent or life-long) forms of toxoplasmosis are associated with specific neurologic and neuropsychiatric symptoms. In the present study, swiss albino mice were inoculated intraperitoneally with 15-20 tissue cysts of the ME-49 strain of Toxoplasma gondii. The brain samples were collected on the days 10, 20, and 30 for determining the histopathological scores and the number of cysts. Furthermore, a real-time quantitative polymerase chain reaction (RT-PCR) was conducted to find out the gene expression levels of the serotonin 2A receptor (5-HTR2A), serotonin 2C receptor (5-HTR2C), serotonin 6 receptor (5-HTR6), serotonin 7 receptor (5-HTR7), and interleukin-6. The results were compared to the histopathological findings of encephalitic toxoplasmosis. The expression levels were observed to increase for all receptors; however at different time points of infection. This experimental model demonstrates that the expression of serotonin receptors was induced in Toxoplasma gondii infections, displaying unique findings for each of the individual receptors.
RESUMO
Hydatid cysts formed by the metacestodes of Echinococcus granulosus. Cattle suffering from hydatid cyst shows fluid-filled structures, especially in liver. These parasite-induced cysts localized by forming fibrous capsules in the liver. Fibrogenesis is the host immune response in the liver against these parasites. Hepatic stellate cells (HSCs) are localized perisinusoidal space also known as vitamin A-storing cells, characterize the important fibrogenic cell type. In this study, livers from 15 animals with hydatid cyst and 8 healthy animals were used. Hematoxylin and Eosin, masson trichrome staining were performed on the prepared liver sections. Microscopically, cysts were bordered eosinophilic necrotic debris blended with degenerate neutrophils, macrophages, eosinophils, lymphocytes, plasma cells and multinucleated giant cells, which extend into the adjacent fibrous connective tissue. In Masson trichrome staining, the fibrous connective tissue was observed surrounding of hydatid cyst. Glial fibrillary acidic protein (GFAP), collagen I, GFAP/collagen I, positive cells were investigated using either indirect single- or double-labeling immunohistochemical staining. The results indicated that anti-GFAP-positive staining was seen in areas including fibrous tissue just under the foreign body giant cells surrounding the cyst wall. In double immunohistochemical staining, it was observed that HSCs labeled with anti-GFAP antibody in the fibrous connective tissue also labeled anti-collagen I antibody. This study shows that HSCs may responsible for synthesis the collagen I in the development of parasitic fibrosis in cystic echinococcosis in the liver of cattle.