Linker Encouraged Solid State Synthesis of MOF Derived Z-Scheme NiCo2O4/NiO/C toward Efficient Removal of Organic and Inorganic Pollutants from Water.

Here, we represent a solid-state route for the construction of MOF derived multifunctional Z-scheme NiCo2O4/NiO/C applied for the photocatalytic removal of methylene blue (dye) and tetracycline (drug) and the reduction of Cr(VI) (heavy metal). The developed solid-state method yielded a highly effective NiCo2O4/NiO/C catalyst by mechanically grinding independently produced Ni and Co-MOFs and subsequently pyrolyzing them. The use of different linkers in the Ni MOF (H3-BTC linker) and Co-MOF (2-methylimidazole linker) proved to be effective in constructing the NiCo2O4/NiO/C composite, ensuring a nonaggregated distribution on a carbon framework. Such a synthesized Z-scheme NiCo2O4/NiO/C composite has performed exceptionally well to achieve excellent degradation of MB (98.23% in 120 min) and TC (92.85% in 25 min) and Cr(VI) reduction (98.22% in 20 min), with excellent recyclability and stability. The NiCo2O4/NiO/C composite, synthesized using Ni and Co-MOFs prepared with different linkers, outperformed its counterpart prepared using Ni and Co-MOFs with identical linkers (either 2-methylimidazole or H3BTC). This study paves the way for the future synthesis of MOF derived bimetallic composites for photocatalytic applications.

Postpartum maternal tachycardia - diagnostic pitfalls!

PURPOSE OF REVIEW: Maternal tachycardia is a common sign with a multitude of causes. We attempt to look at the most common sinister ones in the postpartum period. RECENT FINDINGS: Current guidelines differ in the definition of maternal tachycardia. It has been associated with adverse outcomes such as increased length of stay as well as higher mortality if there is underlying peripartum cardiomyopathy. Some recent studies look at common investigations and how these apply to peripartum women, such as ECG markers of arrhythmogenesis, reference ranges for PCT and echocardiogram findings during pregnancy prior to diagnosis of peripartum cardiomyopathy. SUMMARY: Physiological changes make it difficult to interpret maternal tachycardia and thus how best to manage it. We propose the idea of a three-step approach for the assessment of patients, aiming to identify causes including tachyarrhythmias, obstetric haemorrhage, sepsis, venous thromboembolism and peripartum cardiomyopathy.The first step 'BEDSIDE' applies to all patients looking at observations, history and examination. The second step 'BASIC', applies to most patients and covers ECG and basic blood tests. The final step 'EXTRA' assesses the need for further investigations including additional blood tests and imaging. By using this model, clinicians and healthcare professionals should be able to rationalise the need for more invasive investigations whilst maintain good high-quality care.

Dual PI3Kδγ inhibition demonstrates potent anticancer effects in diffuse large B-cell lymphoma models: Discovery and preclinical characterization of LL-00084282.

Phosphoinositide 3-kinase (PI3K) pathway mediates key signaling events downstream to B-cell receptor (BCR) for survival of mature B-cells, and overexpression or overactivation of PI3Kδ is crucial for B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL). Small molecule PI3Kδγ inhibitors, with a known potential to reduce activated B-cell (ABC)-DLBCL transformation, form an important class of therapeutics approved for follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL). In this study, we describe discovery of a potent, selective and efficacious dual PI3Kδγ inhibitor, LL-00084282, having a differentiated efficacy profile in human ABC- and germinal center B-cell (GCB)-DLBCL cell lines. LL-00084282 displayed high potency and superior PI3Kδγ engagement with excellent selectivity over other PI3K isoforms at both IC50/90 concentrations in biochemical and cell-based assays. In contrast to selective PI3Kδ inhibitors, LL-00084282 showed superior and potent anticancer activity in both ABC- and GCB-DLBCL cell lines. LL-00084282 demonstrated in-vivo efficacy in OCI-Ly10 and SU-DHL-6 xenografts with good tolerability. Furthermore, LL-00084282 inhibited pro-inflammatory cytokine secretion and reduced basophil activation in human PBMCs, showing potential implications in immunoinflammatory conditions. Good pharmacokinetic properties in higher species and desirable efficacy profile highlights potential of this novel PI3Kδγ inhibitor for further clinical evaluation in DLBCL patients.

The obstetric patient in the Covid pandemic: anaesthesia and perioperative care.

PURPOSE OF REVIEW: : The Coronavirus Disease 2019 (COVID-19) pandemic has had an unprecedented impact on pregnant women, maternity services and healthcare workers. We review recent literature on the course of COVID-19 infection in pregnancy, and recommendations for treatment and service provision. RECENT FINDINGS: It has been increasingly recognised that pregnant women are at higher risk of severe disease associated with COVID-19 infection. Early critical care input is crucial to guide respiratory support and techniques such as prone positioning, with a low threshold for intubation in critical illness. Timing of delivery remains a highly individualised decision. Following the RECOVERY trial, the use of a course of steroids in cases of severe COVID-19 infection has been widely adopted, and emerging guidance recommends vaccination in pregnant women. SUMMARY: Rapidly emerging evidence has helped guide clinicians to identify those patients most at risk of severe disease in COVID-19 and implement early interventions to reduce morbidity and mortality.

Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization.

The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing's sarcoma models.

General anaesthesia during caesarean sections: implications for the mother, foetus, anaesthetist and obstetrician.

PURPOSE OF REVIEW: A general anaesthetic is usually given for an emergency caesarean section (Category 1), where there is imminent threat to the mother or foetus. There are many risks in performing a general anaesthetic. The aim of this review is to highlight the effects and risks to the mother and foetus of each step of a general anaesthetic. RECENT FINDINGS: Anaesthetic techniques are changing, and the traditional mantra of using a general anaesthetic for an emergency caesarean sections is being challenged. There are also multiple potential risks of a general anaesthetic that are being better defined. This ranges from awareness during surgery, through to foetal and maternal risks of complications. SUMMARY: This review will outline the different stages of a general anaesthetic and highlight the risks. This summary will allow a better understanding of anaesthetic risks. This will allow obstetricians to have a more informed conversation with an anaesthetist as to form of anaesthetic required (general anaesthetic versus spinal or epidural top-up). The review will also allow obstetricians to give more informed consent to mothers and be aware of the postoperative risks.

Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity.

Repair of uracils in DNA is initiated by uracil DNA glycosylases (UDGs). Family 1 UDGs (Ung) are the most efficient and ubiquitous proteins having an exquisite specificity for uracils in DNA. Ung are characterized by motifs A (GQDPY) and B (HPSPLS) sequences. We report a novel dimeric UDG, Blr0248 (BdiUng) from Bradyrhizobium diazoefficiens. Although BdiUng contains the motif A (GQDPA), it has low sequence identity to known UDGs. BdiUng prefers single stranded DNA and excises uracil, 5-hydroxymethyl-uracil or xanthine from it. BdiUng is impervious to inhibition by AP DNA, and Ugi protein that specifically inhibits family 1 UDGs. Crystal structure of BdiUng shows similarity with the family 4 UDGs in its overall fold but with family 1 UDGs in key active site residues. However, instead of a classical motif B, BdiUng has a uniquely extended protrusion explaining the lack of Ugi inhibition. Structural and mutational analyses of BdiUng have revealed the basis for the accommodation of diverse substrates into its substrate binding pocket. Phylogenetically, BdiUng belongs to a new UDG family. Bradyrhizobium diazoefficiens presents a unique scenario where the presence of at least four families of UDGs may compensate for the absence of an efficient family 1 homologue.

Central neurological complications following obstetric neuraxial blockade.

PURPOSE OF REVIEW: Central neuraxial blockade is increasingly the anaesthetic management of choice for parturients, including in higher risk pregnancies. Although they are usually effective and safe, there are potentially devastating neurological complications that may present either overtly or insidiously. A thorough understanding of the variety of potential neurological complications is essential to adequately consent patients in addition to diagnosing and managing complications following neuraxial anaesthesia. This review aims to describe a number of potential neurological injuries that may occur and suggested management based on available evidence. RECENT FINDINGS: Current evidence supports neuraxial anaesthesia as a safe management strategy in low and many higher risk pregnancies, with a low overall incidence of neurological complications. Neuraxial blockade is safe in patients with platelet counts greater than 70 000/µl and the risk of infective complications secondary to epidural catheterization remains low until day five post procedure. There is also some early evidence supporting the use of transnasal local anaesthetic as a strategy for managing postdural puncture headache. SUMMARY: Difficulty remains in establishing absolute risk of complications and optimal management strategies given the low overall number of patients affected and heterogeneity of therapy. There may be a role for centralized registration of postneuraxial complications in obstetric patients to further develop our collective understanding of these conditions.

Clinical pearls part 3: anaesthetic management of abnormally invasive placentation.

PURPOSE OF REVIEW: Abnormal placentation is a clinical condition seen increasingly in the pregnant population. It is associated with significant morbidity and mortality, which may be mitigated through robust multidisciplinary care for these patients. The role of maternal critical care for these patients has largely been ignored in the literature. RECENT FINDINGS: Advances in pharmacological management of bleeding with recent publications of large multicentre trials in addition to new technologies in the management of massive obstetric haemorrhage (MOH) have revolutionized the management of abnormal placentation. These include the use of tranexamic acid, interventional radiology, cell saver technology, and point-of-care coagulation tests. The role of maternal critical care for the optimization of postoperative complications and physiological derangements has not been considered widely in the literature. This article summarizes the current evidence for interventions and suggests a protocol for the management of these high-risk patients. SUMMARY: A robust protocol outlining the key elements of the management of placenta accreta, including optimizing postoperative care, should be in place to promote desired outcomes.

Traumatic brain injured patients: primum non nocere.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) remains an unfortunately common disease with potentially devastating consequences for patients and their families. However, it is important to remember that it is a spectrum of disease and thus, a one 'treatment fits all' approach is not appropriate to achieve optimal outcomes. This review aims to inform readers about recent updates in prehospital and neurocritical care management of patients with TBI. RECENT FINDINGS: Prehospital care teams which include a physician may reduce mortality. The commonly held value of SBP more than 90 in TBI is now being challenged. There is increasing evidence that patients do better if managed in specialized neurocritical care or trauma ICU. Repeating computed tomography brain 12 h after initial scan may be of benefit. Elderly patients with TBI appear not to want an operation if it might leave them cognitively impaired. SUMMARY: Prehospital and neuro ICU management of TBI patients can significantly improve patient outcome. However, it is important to also consider whether these patients would actually want to be treated particularly in the elderly population.

Curcumin Acrylation for Biological and Environmental Applications.

Curcumin has recently gained interest for use in drug delivery, chemical sensing, and environmental applications. As a result, the development of synthesis strategies for the incorporation of curcumin into novel materials has become a priority. One such strategy, curcumin acrylation, involves the introduction of acrylate functional groups to the curcumin scaffold, with the potential generation of mono-, di-, and triacrylate curcumin species. The relative populations of these species in the resulting multiacrylate mixture can be controlled by the ratio of curcumin to acryloyl chloride in the initial reaction formulation. Characterization of the acrylation reaction and the resulting curcumin multiacrylate product is essential for the effective preparation of new curcumin-containing materials. In this work, a synthesis method for curcumin acrylation is presented and the resulting curcumin multiacrylate product is characterized via various techniques, i.e., HPLC, LCMS, and NMR, as a basis to establish the relationship between synthesis conditions and the extent of acrylation that is achieved.

Clinical 'pearls' of maternal critical care Part 2: sickle-cell disease in pregnancy.

PURPOSE OF REVIEW: The current review outlines the challenges in managing pregnant women with sickle-cell anemia, who are at risk of becoming critically ill during pregnancy. RECENT FINDINGS: Sickle obstetric patients pose unique challenges to the anesthetist and intensivist. We discuss the role of prophylactic transfusions for specific indications like acute anemia and twin pregnancies. The management and prevention of vaso-occlusive crises and chest crisis are also outlined. The role of the multidisciplinary team cannot be overstated.Massive obstetric hemorrhage in this population is difficult, and unique considerations such as cell-saver technology and tranexamic acid usage are discussed. Secondary complications such as pulmonary hypertension and stroke are also considered, with a summary of the latest treatment guidelines. SUMMARY: This is a challenging cohort of pregnant patients who have a significantly increased morbidity and mortality. This review aims to aid management of these patients on the labor ward for both obstetric anesthetists and intensivists.

Clinical 'Pearls' of maternal critical care: part I.

PURPOSE OF REVIEW: This review outlines the challenges in looking after pregnant women with thromboembolism and sepsis who either become or are at risk of becoming critically ill during pregnancy. RECENT FINDINGS: The Pregnancy Mortality Surveillance systems in both the USA and UK record the most common causes of maternal death as thromboembolism and sepsis. Both of these conditions have improved outcomes with timely maternal critical care provided by a multidisciplinary team. SUMMARY: In this review, we discuss the pathophysiology, diagnosis, and management of thromboembolism and sepsis, two very important conditions with high mortality requiring admission to intensive care.

Maternal critical care: 'one small step for woman, one giant leap for womankind'.

PURPOSE OF REVIEW: The purpose of this study is to outline the challenges of looking after women who either become or are at a risk of becoming critically ill during pregnancy. RECENT FINDINGS: In recent years, there has been an increased demand in the need for maternal critical care. This is partly due to women with complex medical conditions surviving to child-bearing age, coupled with improvements in foetal medicine resulting in more high-risk pregnancies reaching term. SUMMARY: In this review, we identify the need for maternal critical care, explore different models of its provision and outline possible benefits and barriers to its future implementation.

Facile synthesis of silver nanoparticles using Calotropis procera leaves: unraveling biological and electrochemical potentials.

HIGHLIGHTS: CPL-AgNPs exhibited improved biomimetic attributes. Antibiotic resistance against pathogens were challenged through use of CPL-AgNPs. Supercapacitor application of facile synthesized AgNPs for the first time demonstrated improved physical application.