Early second-trimester plasma cell free DNA levels with subsequent risk of pregnancy complications

ObjectiveTo investigate the association between cfDNA levels measured during non-invasive prenatal testing (NIPT) and the risk of pregnancy complications in a Chinese population.MethodsThis was a retrospective cohort study of 831 pregnant women who underwent NIPT at 12–22 weeks of gestation. Maternal plasma cfDNA levels and pregnancy outcomes were obtained from NIPT Screening System and hospitalization records, respectively. Logistic regression analysis was performed to investigate the relationship between cfDNA levels and pregnancy complications (after adjusting for confounding factors).ResultsMaternal cfDNA levels were significantly higher in women diagnosed with intrahepatic cholestasis of pregnancy (ICP) and preeclampsia (PE) compared to pregnant women with non-pregnancy complications (NPC) (median cfDNA 7.07, 6.42 vs. 5.99 ng/mL). Increase in cfDNA levels were associated with an increased risk for ICP (adjusted-OR = 1.20, 95% CI: 1.07–1.34) and PE (adjusted-OR = 1.14, 95% CI: 1.02–1.26). In addition, increase in cfDNA levels were associated with risk of GDM, and was dependent on maternal age (maternal age ≥ 35 years: adjusted-OR = 1.16, 95% CI: 1.04–1.29; maternal age < 35 years: adjusted-OR = 0.85, 95% CI: 0.73–0.99).ConclusionMaternal plasma cfDNA levels measured during NIPT are associated with pregnancy complications (ICP, PE and GDM). Maternal age may be an important effect modifier for the association between plasma cfDNA levels and GDM.     

Multi-segment spine kinematics: Relationship with dance training and low back pain

BackgroundSpine posture, range of motion (ROM) and movement asymmetry can contribute to low back pain (LBP). These variables may have greater impact in populations required to perform repetitive spine movements, such as dancers; however, there is limited evidence to support this.Research questionWhat is the influence of dance and LBP on spinal kinematics?MethodsIn this cross-sectional study, multi-segment spinal kinematics were examined in 60 female participants, including dancers (n = 21) and non-dancers (n = 39) with LBP (n = 33) and without LBP (n = 27). A nine-camera motion analysis system sampling at 100 Hz was used to assess standing posture, as well as ROM and movement asymmetry for side bend and trunk rotation tasks. A two-way ANOVA was performed for each of the outcome variables to detect any differences between dancers and non-dancers, or individuals with and without LBP.ResultsCompared to non-dancers, dancers displayed a flatter upper lumbar angle when standing (p < 0.01, ηp² = 0.15), and achieved greater frontal plane ROM for the upper lumbar (p = 0.04, ηp² = 0.08) and lower thoracic (p = 0.02, ηp² = 0.09) segments. There were no differences between dancers and non-dancers for transverse plane ROM (p > 0.05) or movement asymmetry (p > 0.05). There was no main effect for LBP symptoms on any kinematic measures, and no interaction effect for dance group and LBP on spinal kinematics (p > 0.05).SignificanceFemale dancers displayed a flatter spine posture and increased spine ROM compared to non-dancers for a select number of spine segments and movement tasks. However, the overall number of differences was small, and no relationship was observed between LBP and spinal kinematics. This suggests that these simple, static posture, ROM, and asymmetry measures often used in clinical practice can provide only limited generalisable information about the impact of dance or LBP on spinal kinematics.     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

Henoch-Schönlein Purpura Nephritis and Cerebral Venous Sinus Thrombosis Due to Hereditary Deficiency of Antithrombin III

Indian Journal of Pediatrics -     

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.     

Changes in Bone Marrow Adipose Tissue in Transgender and Gender Non-Conforming Youth Undergoing Pubertal Suppression: A Pilot Study

Pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists in transgender and gender non-conforming (TGNC) youth may affect acquisition of peak bone mass. Bone marrow adipose tissue (BMAT) has an inverse relationship with bone mineral density (BMD). To evaluate the effect of pubertal suppression on BMAT, in this pilot study we prospectively studied TGNC youth undergoing pubertal suppression and cisgender control participants with similar pubertal status over a 12-month period. BMD was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Magnetic Resonance T1 relaxometry (T1-R) and spectroscopy (MRS) were performed to quantify BMAT at the distal femur. We compared the change in BMD, T1-R values, and MRS lipid indices between the two groups. Six TGNC (two assigned female and four assigned male at birth) and three female control participants (mean age 10.9 and 11.7 years, respectively) were enrolled. The mean lumbar spine BMD Z-score declined by 0.29 in the TGNC group, but increased by 0.48 in controls (between-group difference 0.77, 95% CI: 0.05, 1.45). Similar findings were observed with the change in trabecular volumetric BMD at the 3% tibia site (-4.1% in TGNC, +3.2% in controls, between-group difference 7.3%, 95% CI: 0.5%-14%). Distal femur T1 values declined (indicative of increased BMAT) by 7.9% in the TGNC group, but increased by 2.1% in controls (between-group difference 10%, 95% CI: -12.7%, 32.6%). Marrow lipid fraction by MRS increased by 8.4% in the TGNC group, but declined by 0.1% in controls (between-group difference 8.5%, 95% CI: -50.2%, 33.0%). In conclusion, we observed lower bone mass acquisition and greater increases in BMAT indices by MRI and MRS in TGNC youth after 12 months of GnRH agonists compared with control participants. Early changes in BMAT may underlie an alteration in bone mass acquisition with pubertal suppression, including alterations in mesenchymal stem cells within marrow.