The role of C-reactive protein and ferritin in the diagnosis of HLH, adult-onset still's disease, and COVID-19 cytokine storm.

Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still's disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS.

Cognitive Abilities and Collaboration in Couples in Type 1 Diabetes Management.

Managing type 1 diabetes involves coordinating complex daily behaviors that may rely on the cognitive abilities of people with diabetes (PWD) and spouses, especially as couples collaborate surrounding diabetes care. The aims of the study were to examine whether ) the cognitive abilities of PWD and their spouses predicted lower A1C, ) collaborating with a spouse with higher cognitive abilities was especially beneficial for PWD with lower cognitive abilities, and ) the benefit of the cognitive abilities of PWD and their spouse occurred through better self-care. Couples ( = 199) were recruited with one member diagnosed with type 1 diabetes (PWD 52% female sex, average age 46.

Relationship satisfaction moderates links between poor sleep quality and psychological distress among couples coping with type 1 diabetes.

Objectives: We examined links between sleep quality and psychological distress among couples dealing with type 1 diabetes (T1D) across cross-sectional and daily diary methods and investigated whether relationship satisfaction moderated these associations.

Methods: 199 persons with T1D and their spouses completed survey questionnaires reporting their own sleep quality, depressive symptoms, and relationship satisfaction. They also completed 14-day diaries reporting their own sleep quality and negative affect.

High-Resolution Spinal Motor Mapping Using Thoracic Spinal Cord Stimulation in Patients With Chronic Pain.

Background: High-resolution spinal cord stimulation (HR-SCS) paddle can stimulate medial-dorsal columns and extend stimulation coverage to the laterally positioned spinal targets.

Objective: To investigate the medio-lateral selectivity of an HR-SCS paddle in patients with chronic pain.

Methods: During standard-of-care spinal cord stimulation (SCS) placement, epidurally evoked electromyography and antidromic dorsal column-evoked potentials were recorded in 12 subjects using an HR-SCS paddle with 8 medio-lateral sites spanning the full epidural width at thoracic T9-12 and a commercial paddle consecutively.

Socioeconomic status in early adolescence predicts blunted stress responses in adulthood.

Individuals who grow up in families with lower socioeconomic status (SES) tend to experience disproportionate rates of chronic stress. The "freeze" response, characterized by blunted cardiovascular reactivity and reduced engagement with the environment, is associated with chronic stress and may be utilized when an individual is unable to escape or overcome environmental stressors. Using a diverse community sample of 184 adolescents followed from the age of 13 to 29 years, along with their friends and romantic partners, this study examined links between family SES and stress responses in adulthood.

Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study.

Background: Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab.

Perceived social support and ambulatory blood pressure during daily life: a meta-analysis.

Perceived social support has been linked to lower rates of morbidity and mortality. However, more information is needed on the biological mechanisms potentially responsible for such links. The main aim of this paper was to conduct a meta-analytic review of the association between perceived social support and awake ambulatory blood pressure (ABP) which is linked to cardiovascular morbidity and mortality.

Dexmedetomidine Use in Intensive Care Unit Sedation and Postoperative Recovery in Elderly Patients Post-Cardiac Surgery (DIRECT).

Objective: This study examined recovery, delirium, and neurocognitive outcome in elderly patients receiving dexmedetomidine or propofol sedation after undergoing cardiac surgery.

Design: Open-label randomized trial.

Setting: Single center.

Couples Managing Type 1 Diabetes Using Diabetes Technology.

Objective: Diabetes technology has improved the lives of people with diabetes (PWD), but there is little research on how insulin pumps and continuous glucose monitoring (CGM) affect couples' relationships. The purpose of this study was to examine how the use of diabetes technology affects couple interactions.

Methods: In a secondary data analysis, we used a multiple-method qualitative analysis, including a constant-comparison approach, to examine similarities and differences in couple interactions related to diabetes technology.

Differences in EEG patterns between tonic and high frequency spinal cord stimulation in chronic pain patients.

Objective: To investigate the differences in neural patterns between spinal cord stimulation (SCS) waveforms (60-Hz tonic vs 10-KHz high frequency stimulation, HFS) and their correlation to stimulation-induced pain relief.

Methods: We recorded 10-channel electroencephalogram (EEG) in response to stimulation ON and OFF in 9 chronic pain patients (4 women, 5 men) during SCS surgery and examined the intraoperative spatio-spectral EEG features.

Results: We discovered stronger relative alpha power in the somatosensory region and higher trend in alpha/theta peak power ratio in frontal cortex with HFS.

A review of the electronic two-week rule referrals for head and neck cancer to Western Sussex Hospitals NHS Foundation Trust.

Introduction The two-week rule (2WR) for referring suspected malignancies aims to improve access and outcomes for cancer patients. However, there has been criticism of the rule in the literature. GDPs have an important role in spotting head and neck cancer (HNC) and using the 2WR appropriately to ensure their patients get fast and effective treatment.

Palladium Catalyzed Hydrodefluorination of Fluoro-(hetero)arenes.

Palladium catalyzed hydrodefluorination was developed for fine-tuning the properties of fluoro-(hetero)aromatic compounds. The robust reaction can be set up in air, requires only commercially available components, and tolerates a variety of heterocycles and functionalities relevant to drug discovery. Given the prevalence of fluorine incorporation around metabolic hotspots, the corresponding deuterodefluorination reaction may prove useful for converting fluorinated libraries to deuterated analogues to suppress the oxidative metabolism by kinetic isotope effects.

Validation of anti-glucocerebrosidase antibodies for western blot analysis on protein lysates of murine and human cells.

Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the gene, encoding the lysosome-resident glucocerebrosidase enzyme involved in the hydrolysis of glucosylceramide. The discovery of an association between mutations in and the development of synucleinopathies, including Parkinson disease, has directed attention to glucocerebrosidase as a potential therapeutic target for different synucleinopathies. These findings initiated an exponential growth in research and publications regarding the glucocerebrosidase enzyme.

Intraoperative Neuromonitoring in Percutaneous Spinal Cord Stimulator Placement.

Introduction: Placement of spinal cord stimulation (SCS) paddles under general anesthesia using intraoperative neuromonitoring (IONM) has been shown to be associated with equivocal or superior clinical outcomes in comparative studies. The value of IONM in percutaneous permanent SCS placement has not been demonstrated.

Methods: Outcomes for patients under percutaneous SCS placement performed with IONM were prospectively collected.

Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS).

The lipid kinase phosphoinositide 3-kinase γ (PI3Kγ) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3Kγ, we discovered a series of azaisoindolinones as selective, brain penetrant inhibitors of PI3Kγ. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy in murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

Glucocerebrosidase haploinsufficiency in A53T α-synuclein mice impacts disease onset and course.

Mutations in GBA1 encountered in Gaucher disease are a leading risk factor for Parkinson disease and associated Lewy body disorders. Many GBA1 mutation carriers, especially those with severe or null GBA1 alleles, have earlier and more progressive parkinsonism. To model the effect of partial glucocerebrosidase deficiency on neurological progression in vivo, mice with a human A53T α-synuclein (SNCA) transgene were crossed with heterozygous null gba mice (gba).

Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene.

Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p.

The consultant practitioner: an evolving role to meet changing NHS needs.

Unlabelled: Since the introduction of the consultant practitioner role, with its huge variability in purpose and context, it has had to evolve in response to the changing needs of the NHS to achieve sustainability and transformation of services.

Aim: This article reflects on the relevance of the consultant practitioner role and the impact of an action learning set in hastening its evolution in one NHS foundation trust.

Method: From a process of collective critical reflection on their practice, six consultant practitioners analysed the impact they have had on influencing services and empowerment of their patients.

Life satisfaction and inflammation in couples: an actor-partner analysis.

Life satisfaction has been linked to lower cardiovascular disease mortality. However, much less is known about the biological mechanisms linking life satisfaction to physical health. In addition, the dyadic context of life satisfaction has not been considered despite increasing evidence that partners influence each other in health-relevant ways.

Depth-dependent effects of culling-do mesophotic lionfish populations undermine current management?

Invasive lionfish ( and ) have spread widely across the western Atlantic and are recognized as a major threat to native marine biodiversity. Although lionfish inhabit both shallow reefs and mesophotic coral ecosystems (MCEs; reefs from 30 to 150 m depth), the primary management response implemented by many countries has been diver-led culling limited to reefs less than 30 m. However, many reef fish undergo ontogenetic migrations, with the largest and therefore most fecund individuals found at greatest depths.

Supporting clinical leadership through action: The nurse consultant role.

Aims And Objectives: To evaluate the effectiveness of an action learning set to enhance clinical leadership and extend their scope and confidence more strategically.

Background: As the most senior clinical role in most healthcare systems, the consultant nurse role is a solitary one. They are required to develop personal resilience, commitment and a belief in their ability to lead, with new consultants needing a strong support network to succeed.

Prospective Study of the Use of Intraoperative Neuromonitoring in Determining Post-Operative Energy Requirements and Physiologic Midline in Spinal Cord Stimulation.

Background: Intraoperative neuromonitoring (IONM) through electromyography (EMG) studies has been shown to be a safe, effective way to determine the laterality of the spinal cord and guide electrode placement during spinal cord stimulation (SCS). However, the use of IONM to predict post-operative energy requirements and midline has not been examined and offers a new avenue to streamline programming and device selection. Further, the impact of cerebrospinal fluid (CSF) thickness on intraoperative and post-operative amplitudes is understood but has not been explicitly characterized.

Efferocytosis is impaired in Gaucher macrophages.

Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 and Rab7.

Molecular lock regulates binding of glycine to a primitive NMDA receptor.

The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants.