Modifiable Determinants of Postpartum Weight Loss in Women with Obesity: A Secondary Analysis of the UPBEAT Trial

Pregnancy can alter a woman’s weight gain trajectory across the life course and contribute to the development of obesity through retention of weight gained during pregnancy. This study aimed to identify modifiable determinants associated with postpartum weight retention (PPWR; calculated by the difference in pre-pregnancy and 6 month postpartum weight) in 667 women with obesity from the UPBEAT study. We examined the relationship between PPWR and reported glycaemic load, energy intake, and smoking status in pregnancy, excessive gestational weight gain (GWG), mode of delivery, self-reported postpartum physical activity (low, moderate, and high), and mode of infant feeding (breast, formula, and mixed). At the 6 month visit, 48% (n = 320) of women were at or above pre-pregnancy weight. Overall, PPWR was negative (−0.06 kg (−42.0, 40.4)). Breastfeeding for ≥4 months, moderate or high levels of physical activity, and GWG ≤9 kg were associated with negative PPWR. These three determinants were combined to provide a modifiable factor score (range 0–3); for each added variable, a further reduction in PPWR of 3.0 kg (95% confidence interval 3.76, 2.25) occurred compared to women with no modifiable factors. This study identified three additive determinants of PPWR loss. These provide modifiable targets during pregnancy and the postnatal period to enable women with obesity to return to their pre-pregnancy weight.     

Restarting LDLT During COVID-19: Early Results After Restructuring

IntroductionLiving-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic.Materials and MethodsThe changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months).ResultsNineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected.ConclusionThis study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.     

Can Bariatric Surgery be Performed Safely in Patients with Severe Treatment-Resistant Asthma?

Obesity-associated severe asthma is a distinct phenotype characterised by resistance to standard asthma therapies. Bariatric surgery appears to be a viable alternative for those who have failed trials of traditional weight loss methods. However, anaesthetic and surgical risks are potential barriers. We describe three patients with treatment-resistant obesity-associated severe asthma who underwent bariatric surgery without complications due to the multidisciplinary perioperative planning and care involved in these complex cases. All three patients showed improvements in asthma control and reduction in maintenance medication use post-surgery.     

Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6 rat glial cells

Neuroinflammation plays a significant role in various chronic and acute pathological conditions of the central nervous system. In the Indian system of medicine, Pluchea lanceolata is used to treat the neurological disorders. We investigated the effect of major pentacyclic triterpene and its naturally occurring acetate derivative isolated from P. lanceolata on lipopolysaccharide (LPS)-stimulated neuroinflammatory condition associated to inflammatory cytokine production in rat astrocytoma cell line (C6). The log concentration dependence of Pluchea bioactive taraxasterol (Tx) significantly (p?<?0.05) attenuates the release of pro-inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, while its in situ produced acetyl derivative, i.e., taraxasterol acetate (TxAc), did not inhibit the LPS-induced IL-6 production at lower concentration (p?>?0.05). Surflex-Dock molecular modeling study was performed to simulate the binding capacity of compounds into the active site of the TNF-α (2AZ5), tumor protein P53 (2VUK), and NF-kappa-B (1RAM). The differential inhibition of cytokines by Tx and TxAc was further confirmed by high docking scores showing the high affinity to target proteins. Findings of the study demonstrated the comparatively greater role of Pluchea triterpene than its in situ produced acetate derivate in neuroinflammation-associated disorders.     

Emerging role of non‐coding RNA in health and disease

Metabolic Brain Disease - Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease...     

Groups of coevolving positions provide drug resistance to Mycobacterium tuberculosis: A study using targets of first-line antituberculosis drugs

Drug resistance has been associated with point mutations in coding regions leading to an altered protein sequence and structure. Such changes have been seen as isolated events occurring at various positions in a sequence. However, we hypothesise that it is not a single mutation at a specific position but a group of positions that coevolve in a correlated fashion to increase the fitness of a target protein against a drug. To prove the hypothesis, selected protein sequences of Mycobacterium tuberculosis drug resistance genes were successfully screened using a bioinformatics approach to detect groups of coevolving amino acids at important structural and functional positions in the targets of first-line antituberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide). The algorithmically characterised genetic mutations and the lineage-specific single nucleotide polymorphisms (SNPs) detected previously in drug resistance genes of M. tuberculosis complex genomes were also found in the identified coevolving groups. Mapping of coevolving positions to the secondary structure of proteins clearly indicates the preference of amino acid residues in the helix to coevolve. Moreover, active-site residues of some candidate proteins were also found in coevolving groups. The coevolving groups detected in this study will be useful to gain new insights into the molecular and evolutionary basis of drug resistance. This work provides an important first step towards finding solutions to the multidrug resistance problem through coevolution analysis of proteins, in turn helping to develop new drug regimens against pathogens, including M. tuberculosis.     

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.     

Beyond the snare: technically accessible large en bloc colonic resection in the West: an animal study

Background: Endoscopic submucosal dissection (ESD) and circumferential submucosal incision endoscopic mucosal resection (CSI‐EMR) are techniques for en bloc excision of large sessile colonic lesions. Our aims were to compare the efficacy, safety and learning curve of colonic hybrid knife (HK) ESD versus CSI‐EMR for en bloc excision of 50 mm diameter hemi‐circumferential artificial lesions in a porcine model. Patients and Methods: Two separate 50 mm diameter areas of normal recto‐sigmoid mucosa were marked out in each of ten pigs. One was excised with HK‐ESD using succinylated gelatin (SG) submucosal injection. The other was isolated with CSI with the Insulated Tip Knife 2 followed by SG submucosal injection then EMR with a large snare. Euthanasia and colectomy was performed at 72 h followed by blinded histopathology assessment. Results: En bloc excision rates were: HK‐ESD 100% versus CSI‐EMR 20% (P = 0.008). The mean number of resections per lesion was HK‐ESD 1 versus CSI‐EMR 3 (P = 0.001). The mean dimensions of the largest specimen per technique were HK‐ESD 63 × 54 mm versus CSI‐EMR 49 × 41 mm (P = 0.005). Procedure duration mean was HK‐ESD 54 min versus CSI‐EMR 22 min (P < 0.001). When procedure duration was adjusted for the size of the resected en bloc specimen, a statistically significant and accelerated learning effect was noted for HK‐ESD (r = ?0.83, P = 0.003). There were no perforations and no significant bleeding. Conclusions: HK‐ESD with SG submucosal injection is superior to CSI‐EMR for en bloc excision of 50 mm diameter lesions in a porcine model. The technique is rapidly learnt. This novel approach may lower the barrier to colonic ESD for Western endoscopists.