Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms.

Nociplastic pain is a mechanistic term used to describe pain that arises or is sustained by altered nociception, despite the absence of tissue damage. Although nociplastic pain has distinct pathophysiology from nociceptive and neuropathic pain, these pain mechanisms often coincide within individuals, which contributes to the intractability of chronic pain. Key symptoms of nociplastic pain include pain in multiple body regions, fatigue, sleep disturbances, cognitive dysfunction, depression and anxiety.

Invasive pulmonary aspergillosis in the intensive care unit: current challenges and best practices.

The prevalence of invasive pulmonary aspergillosis (IPA) is growing in critically ill patients in the intensive care unit (ICU). It is increasingly recognized in immunocompetent hosts and immunocompromised ones. IPA frequently complicates both severe influenza and severe coronavirus disease 2019 (COVID-19) infection.

Discovery of novel polyamide-pyrrolobenzodiazepine hybrids for antibody-drug conjugates.

Pyrrolobenzodiazepine (PBD) dimers are well-known highly potent antibody drug conjugate (ADC) payloads. The corresponding PBD monomers, in contrast, have received much less attention from the ADC community. We prepared several novel polyamide-linked PBD monomers and evaluated their utility as ADC payloads.

Stroke and Chronic Kidney Disease.

Chronic kidney disease (CKD) is strongly associated with the full spectrum of cerebrovascular disease including ischaemic and haemorrhagic stroke, small vessel disease, and vascular cognitive impairment. Shared conventional vascular risk factors such as age, hypertension, and diabetes mellitus may account for many of these associations, but novel renal-specific risk factors such as uraemia-related coagulopathy or endothelial dysfunction have also been proposed. In this chapter, we will explore the impact of CKD on stroke risk, mechanisms, and outcomes.

Online Search Trends Influencing Anticoagulation in Patients With COVID-19: Observational Study.

Background: Early evidence of COVID-19-associated coagulopathy disseminated rapidly online during the first months of 2020, followed by clinical debate about how best to manage thrombotic risks in these patients. The rapid online spread of case reports was followed by online interim guidelines, discussions, and worldwide online searches for further information. The impact of global online search trends and online discussion on local approaches to coagulopathy in patients with COVID-19 has not been studied.

Methods of Skull Base Repair Following Endoscopic Endonasal Tumor Resection: A Review.

Following the introduction of fully endoscopic techniques for the resection of pituitary tumors, there was a rapid expansion of the indications for endonasal endoscopic surgery to include extrasellar tumors of the skull base. These techniques offer significant advantages over traditional open surgical approaches to the skull base, including improved tumor resection, and better post-operative neurological outcomes. Following their introduction, however, the initial rate of post-operative CSF leak was unacceptably high.

Clinical application of three-dimensional printing to the management of complex univentricular hearts with abnormal systemic or pulmonary venous drainage.

In recent years, three-dimensional printing has demonstrated reliable reproducibility of several organs including hearts with complex congenital cardiac anomalies. This represents the next step in advanced image processing and can be used to plan surgical repair. In this study, we describe three children with complex univentricular hearts and abnormal systemic or pulmonary venous drainage, in whom three-dimensional printed models based on CT data assisted with preoperative planning.

Predictors of poor outcome among children with heterotaxy syndrome: a retrospective review.

Objective: To determine predictors of poor outcome in patients with heterotaxy syndrome.

Methods: A retrospective review of children with heterotaxy syndrome, in a single tertiary paediatric cardiology centre, was conducted between 1 January 1997 and 1 January 2014 to determine predictors of poor outcome. Poor outcome was defined as death, cardiac transplantation or New York Heart Association (NYHA) functional class III or IV.

Successful slide tracheoplasty and partial atrioventricular septal defect repair following extracorporeal membrane oxygenation support.

A two-year-old boy with a background history of Down syndrome and partial atrioventricular septal defect presented with acute respiratory distress requiring intubation and mechanical ventilation. He continued to deteriorate, despite ventilation; direct laryngoscopy, bronchoscopy, and computed tomography demonstrated severe long segment tracheal stenosis. He was placed on extracorporeal membrane oxygenation to stabilise his condition.

A case of parvovirus B19-induced pure red cell aplasia in a child following heart transplant.

We describe a case of an 11-year-old boy who underwent orthotopic heart transplant for dilated cardiomyopathy. He developed a normocytic, normochromic anaemia with a low reticulocyte count 1 month after transplant. A bone marrow biopsy was performed, which showed a mildly hypocellular bone marrow with few red blood cell precursors with giant pro-erythroblasts indicative of a pure red cell aplasia.

Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors.

This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 Å, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected.