Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway.

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.

Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats.

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203 nm, a zeta potential of -38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment.

The Use of Sequential Integrated Screening to Stratify Risk in Monochorionic-Diamniotic Twin Pregnancies.

OBJECTIVE: This study aimed to identify differences in sequential integrated screening and early ultrasound markers in monochorionic/diamniotic (MC/DA) pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) and unequal placental sharing (UPS). STUDY DESIGN: Retrospective cohort study of MC/DA pregnancies evaluated between January 2012 and July 2017 at the University of California San Francisco. MC/DA pregnancies with ultrasound surveillance up to 26 weeks who participated in the California Prenatal Screening Program (CPSP) were included. Pregnancies with structural or genetic anomalies were excluded. UPS was defined as an intertwin growth discordance ≥20%. Intertwin nuchal translucency (NT) discordance was calculated by the absolute value of the difference of the NT of cotwins. Kruskal-Wallis or ANOVA testing was performed where appropriate, and negative binomial regression models were chosen to test for differences in mean biomarker levels by outcome group. RESULTS: A total of 191 MC/DA pregnancies were included; 85 were affected by TTTS, 35 by UPS, and 71 controls. Significant differences in intertwin NT discordance in pregnancies complicated by TTTS and UPS compared with controls (p = 0.007) were found. TTTS cases had a mean NT discordance greater than two times that of controls (p = 0.04), while UPS cases had a value more than three times greater (p = 0.003). There was a statistically significant difference in mean second trimester human chorionic gonadotropin (hCG) between the cohorts (p = 0.0002) with TTTS cases having a mean second trimester hCG value 1.5 greater than both controls (p < 0.001) and UPS cases (p = 0.001). Analysis showed a significant difference in mean second trimester inhibin between the three cohorts (p = 0.029). Pregnancies complicated by UPS had a mean second trimester inhibin 1.5 times greater than controls (p = 0.010). CONCLUSION: Our study shows that there are unique differences in early ultrasound and sequential integrated serum markers between MC/DA gestations complicated by TTTS and UPS versus those unaffected. KEY POINTS: · Differences exist in sequential integrated screening markers in monochorionic-diamniotic twin pregnancies.. · Early risk stratification of monochorionic-diamniotic twin pregnancies may be possible.. · Sequential integrated screening testing can provide useful information to clinicians when evaluating monochorionic-diamnitoic twin pregnancies..

The multidisciplinary approach to the care of the obese parturient.

Maternal obesity in pregnancy is associated with increased maternal and fetal risks. Pregnancy management should include counseling, screening, and optimization of maternal health, increased fetal surveillance, and preparation for parturition. A multidisciplinary approach should be implemented including collaboration from obstetricians, nutritionists, anesthesiologists, social workers, and neonatologists to optimize perinatal outcomes. Pregnancy is an ideal window of opportunity to influence both the patient's long-term health and the health of the offspring.

Biomedical features of flaxseed against different pathologic situations: A narrative review.

Flaxseed is a plant that grows and is cultivated in more than 50 countries; the main flax producer countries are Canada, China, the United States, and India. The purpose of the present study was to overview the source, chemical compounds, and mechanisms of the therapeutic effects of this valuable plant. For writing this manuscript, we made a list of relevant keywords and phrases, and then we started searching for studies in PubMed, Scopus, and Web of Science databases. The main constituents of flaxseed include lipids, proteins, lignans, fibers, and minerals. Flaxseed is full of antioxidants such as tocopherols, betacarotene, cysteine, and methionine which result in a decrease in blood pressure, heart disease, hepatic and neurological disorders, and increased insulin sensitivity. Flaxseed is commonly used for its antidiabetic and anticancer activities and also it is beneficial for cardiovascular, gastrointestinal, hepatic, urological, and reproductive disorders, and because of these beneficial effects, it is recognized as a medical plant.

Does the 1-step method of gestational diabetes mellitus screening improve pregnancy outcomes?

BACKGROUND: Despite considerate debate, the best method of diagnosing gestational diabetes mellitus remains unknown. A commonly used method of gestational diabetes mellitus screening in the United States is the 2-step method, which includes screening with a 50-gram, 1-hour glucose challenge followed by a 100-gram, 3-hour diagnostic oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Group has recommended the 1-step method using a 75-gram, 2-hour oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Group thresholds have been predicted to increase the rates of gestational diabetes mellitus, yet little is known about the effect on pregnancy outcomes, especially in the United States. OBJECTIVE: This study aimed to determine whether adoption of the 1-step method of gestational diabetes mellitus screening leads to improved obstetrical outcomes at a single academic institution. STUDY DESIGN: This is a retrospective cohort study of patients who delivered before and after a switch from the 2-step method to the 1-step International Association of Diabetes and Pregnancy Study Group method in July 2015. Women with a due date of January 1, 2012 through October 1, 2015 were diagnosed with gestational diabetes mellitus using the 2-step method with Carpenter and Coustan criteria. After a 6-month transition period, outcomes from women with a due date of May 1, 2016 through February 1, 2018, when the 1-step International Association of Diabetes and Pregnancy Study Group criteria were used to diagnose gestational diabetes mellitus, were evaluated. Women with gestational diabetes mellitus were managed similarly throughout the study period. The primary outcome was the incidence of primary cesarean delivery. Maternal and neonatal outcomes were compared using chi-square and t tests, and multivariable logistic regression was used to control for changes in the population. RESULTS: With the adoption of the International Association of Diabetes and Pregnancy Study Group method, the rates of gestational diabetes mellitus more than doubled, to 23.3% from 9.2% (P<.001). The rates of primary cesarean delivery increased with the International Association of Diabetes and Pregnancy Study Group criteria (22.2% vs 19.4%, P=.001), and the incidence of shoulder dystocia was not significantly different (1.1% vs 0.8%, P=.07). The rate of preeclampsia decreased during the time the 1-step method was in use (8.2% vs 10.9%, P<.001). The rate of macrosomia was not different using a definition of ≥4500 g (0.99% vs 0.86%, P=.5) but was reduced when using a definition of ≥4000 g (8.0% vs 6.0%, P<.001). The rate of neonatal intensive care unit admission did not change significantly. Controlling for maternal age, body mass index, race or ethnicity, chronic hypertension, and parity, the adjusted odds of a diagnosis of gestational diabetes mellitus increased 3-fold (adjusted odds ratio, 3.3; 95% confidence interval, 2.90-3.66) with 1-step testing, the adjusted odds of a shoulder dystocia increased (adjusted odds ratio, 1.48; 95% confidence interval, 0.97-2.25), and the adjusted odds of preeclampsia decreased (adjusted odds ratio, 0.64; 95% confidence interval, 0.55-0.74). There was no change in the adjusted odds of primary cesarean delivery (adjusted odds ratio, 1.05; 95% confidence interval, 0.94-1.17). CONCLUSION: Although the rates of gestational diabetes mellitus increased 3-fold with the adoption of the International Association of Diabetes and Pregnancy Study Group method, the rates of primary cesarean delivery, shoulder dystocia, and birthweight ≥4500 g did not decrease in our population. The incidence of preeclampsia decreased; our analysis suggests that this was not because of the increased diagnosis of gestational diabetes mellitus. In our patient population, a large increase in the rates of gestational diabetes mellitus did not lead to an improvement in several clinically meaningful obstetrical outcomes.

COVID-19 and multiorgan failure: A narrative review on potential mechanisms.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in December 2019 form Wuhan, China leads to coronavirus disease 2019 (COVID-19) pandemic. While the common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. The involvement of different organs in severe patients results in lengthening the hospitalization duration and increasing the mortality rate. In this review, we aimed to investigate the involvement of different organs in COVID-19 patients, particularly in severe cases. Also, we tried to define the potential underlying mechanisms of SARS-CoV2 induced multiorgan failure. The multi-organ dysfunction is characterized by acute lung failure, acute liver failure, acute kidney injury, cardiovascular disease, and as well as a wide spectrum of hematological abnormalities and neurological disorders. The most important mechanisms are related to the direct and indirect pathogenic features of SARS-CoV2. Although the presence of angiotensin-converting enzyme 2, a receptor of SARS-CoV2 in the lung, heart, kidney, testis, liver, lymphocytes, and nervous system was confirmed, there are controversial findings to about the observation of SARS-CoV2 RNA in these organs. Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs. Therefore, further investigations are needed to detect the exact mechanisms of pathogenesis. Since the involvement of several organs in COVID-19 patients is important for clinicians, increasing their knowledge may help to improve the outcomes and decrease the rate of mortality and morbidity.

Implementation of a universal cervical length screening program: identifying factors associated with decline rates.

PURPOSE: Cervical length (CL) measurement is now accepted as a screening strategy for identifying women at risk for preterm birth (PTB). However, patient acceptability may limit its implementation. Our objective was to identify characteristics associated with women who decline this screening. MATERIALS AND METHODS: This is a secondary analysis of a prospective cohort study of women offered UCL screening from January 2012 to June 2012. Women with a singleton gestation 18 0/7-23 6/7 weeks at the time of anatomy scan were included. Trained sonographers were instructed to perform UCL screening on all eligible patients using an "opt-out" approach. Chi square statistics and Wilcoxon rank sum tests were used to compare categorical and continuous data, where appropriate. Logistic regression was used to calculate odds ratio for factors associated with declining UCL screening Results: 1348 women were offered CL screening; 131 (9.7%) declined. Overall, multiparous women were more than twice as likely to decline UCL screening compared to primiparous women [OR 2.4 (1.6-3.8)]. Patient acceptance of screening was significantly dependent on the sonographer (p < .05). CONCLUSION: Multiparous women are less likely to accept this strategy of PTB prevention. A standardized counseling approach may improve patient acceptance and mitigate variability in acceptance rates observed amongst sonographers.

Prenatal care in a specialized diabetes in pregnancy program improves compliance with postpartum testing in GDM women.

OBJECTIVE: To evaluate whether prenatal care in a specialized diabetes in pregnancy program (DMC) improves compliance with completion of the 2-h 75 g oral glucose tolerance test (2HrOGTT) in GDM women. METHODS: A retrospective cohort study of GDM women delivering in a university health system between January 2011 and March 2014 was performed. Women were divided into two groups: those receiving care in prenatal clinics over an 18-month period prior to the establishment of the diabetes in pregnancy clinic (pre-DMC) and those receiving prenatal care in a specialized diabetes in pregnancy clinic (post-DMC). The primary outcome was completion of the 2HrOGTT postpartum. Clinical characteristics associated with 2HrOGTT completion were evaluated. Time trend analysis was performed to evaluate month to month variation in 2HrOGTT compliance for secular trends. RESULTS: A total of 292 women were analyzed, 147 post-DMC and 118 pre-DMC. The 2HrOGTT was ordered more frequently in the post-DMC compared to pre-DMC (90.0 versus 53.0%, p < 0.0001). Rates of completion of the 2HrOGTT were 49.2% post-DMC and 25.0% pre-DMC, p = 0.007. After adjusting for potential confounders, women who received prenatal care post-DMC were 2.98 times more likely to complete the 2HrOGTT compared to those receiving care pre-DMC (OR 2.98 [1.34, 6.62], p = 0.007). CONCLUSIONS: Providers were 5.9 times more likely to order the recommended testing for GDM women who attended the postpartum visit in the post-DMC period. GDM women who receive prenatal care in a specialized diabetes in pregnancy program are more likely to complete the 2HrOGTT in the postpartum period.

Placental microRNA Expression Is Not Altered by Maternal Obesity and Fetal Overgrowth.

Objective The epigenetic mechanisms underlying fetal metabolic programming are poorly understood. We studied whether obesity is associated with alterations in placental miRNA expression. Study Design A cross-sectional study was performed, including (1) normal-weight women (BMI 20-24.9 kg/m2) and normal-birth-weight (BW) infants (2,700-3,500 g) (n = 20), (2) normal-weight and macrosomic infants (BW ≥ 4,000 g) (n = 10), (3) obese (BMI ≥ 35 kg/m2) and normal BW infants (n = 16), and (4) obese and macrosomic infants (n = 10). All had term deliveries (37-41 weeks) and normal glucose tolerance (1 hour GCT < 7.2 mmol/L [130 mg/dL]). The expression of 5,639 placental miRNAs was assessed using miRNA microarray. Differential miRNA expression was determined using two-way ANOVA and pairwise contrasts, with the Benjamini-Hochberg (BH) correction. MiRNAs with Z-scores ≥ 2 and false discovery rate (FDR) < 20% were considered significant. Results Principal components analysis demonstrated similar global miRNA expression profiles among groups. Of 5,639 miRNAs, only 5 were significantly different between obese and controls, which were not validated by quantitative polymerase reaction. Conclusion There was no difference in placental miRNA expression associated with obesity or overgrowth. Aberrant placental miRNA expression is an unlikely mechanism underlying fetal metabolic programming related to maternal obesity.

The Effect of an Obesogenic Maternal Environment on Expression of Fetal Umbilical Cord Blood miRNA.

OBJECTIVE: Exposure to maternal obesity in utero predisposes offspring to obesity and metabolic disease. This study investigated whether maternal obesity is associated with alterations in expression of fetal microRNA (miRNA). STUDY DESIGN: A cohort study of women with body mass index (BMI) ≥35 kg/m(2) (n = 16) versus those with normal BMI 20 to 24.9 (n = 20) was performed. All participants had normal glucose tolerance (1-hour glucose challenge test <130) and normally grown neonates (2700-3500 g). Umbilical cord samples were collected immediately after delivery. Expression of miRNA was assessed using Affymetrix GeneChip miRNA 3.0 Arrays. Differential miRNA expression was determined using Student t tests with Benjamini-Hocherg correction. RESULTS: For 1733 human mature miRNAs, the expression levels were not statistically different in umbilical cord blood samples from pregnancies of obese women compared to controls. CONCLUSION: Expression of fetal miRNA is not altered in umbilical cord blood in response to in utero exposure to obesity. Alternate mechanisms underlying the fetal effects of maternal obesity should be explored.

Antipsychotics leading to neuroleptic malignant syndrome in pregnancy.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is characterized by a tetrad of mental status changes, extrapyramidal symptoms, hyperpyrexia, and autonomic instability and can develop after the use of antipsychotics. CASE: A young, multiparous woman presented at 26 weeks of gestation with acute psychosis and was treated with haloperidol until she developed rigidity of her extremities and then was switched to risperidone. She subsequently developed mental status changes, rigidity, hyperthermia, and autonomic instability, leading to a diagnosis of NMS. Risperidone was discontinued and, owing to ongoing psychosis, olanzapine was initiated. Subsequently, her symptoms resolved. CONCLUSION: Neuroleptic malignant syndrome may complicate the treatment of pregnant women using antipsychotics. Clinicians should take into account the risks of untreated psychosis when discontinuing the offending agent and consider initiating alternative pharmacotherapy.

Enteric duplication cysts of the pancreas: a report of two cases and review of the literature.

Enteric duplication cysts are rare congenital malformations that are most commonly diagnosed in children. Enteric duplications associated with the pancreas are especially uncommon, and may present with specific clinical findings such as severe pancreatitis. These cysts often pose unique surgical challenges. In addition, the diagnosis of pancreatic duplication cysts is often difficult, and may be confused with pancreatic pseudocysts or neoplasms. Herein we report two cases of pancreatic duplication cysts, and present a complete tabulation of all case reports of pancreatic-associated duplication cysts reported in the English literature. We conclude that pancreatic duplication cysts are a rare entity, most commonly found to occur in infants and children. We further find that although severe complications may arise as a result of their presentation and treatment, the rate of post-operative complications in patients between 3 and 21 years of age is extremely low, with the highest complication rate occurring in a bimodal distribution (<3-years and >21-years of age). Despite complications in the youngest and older patient populations, surgical excision remains the mainstay of therapy for pancreatic duplication cysts in all age groups.