Cytokines and Epidermal Lipid Abnormalities in Atopic Dermatitis: A Systematic Review.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors.

Use of orthotics with orthotic sandals versus the sole use of orthotics for plantar fasciitis: Randomised controlled trial.

Background: Plantar fasciitis (PF) affects around 10% of the population. Prefabricated orthotics with arch support has been shown to provide symptom relief in PF by decreasing the repetitive stress sustained by the plantar fascia. However, prefabricated orthotics are only effective when shoes are worn, meaning the foot may be left unsupported when it is impractical to wear shoes.

Does orthotics use improve comfort, speed, and injury rate during running? A randomised control trial.

Background: Running is a hugely popular sport. Unfortunately, running-related injury (RRI) rates are high, particularly amongst amateur and recreational runners. Finding ways to reduce RRI rates and maximise comfort and performance for runners is important.

The blood proteomic signature of prurigo nodularis reveals distinct inflammatory and neuropathic endotypes: A cluster analysis.

Background: Prurigo nodularis (PN) is an extremely pruritic, chronic inflammatory skin disease. Little is known about systemic inflammation in PN.

Objective: To characterize plasma inflammatory biomarkers in patients with PN and investigate the presence of disease endotypes.

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis.

Importance: Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease.

Objective: To elucidate which components of type 2 inflammation are dysregulated systemically in PN.

Design: Whole blood was obtained from PN patients with uncontrolled disease and control patients without pruritus.

Unnecessary Cervical Discectomy - A simple test to differentiate between Cervical and Shoulder Pathology: A Case Report.

Background: Diagnostic dilemma exists in differentiating between neck and shoulder pathology, as both can give a rise to shoulder and arm symptoms. In addition, the hypersensitivity of magnetic resonance imaging (MRI) scans may wrongly highlight non-clinically significant changes as potential targets for surgical intervention. The arm- squeeze test is a recognised recognized method used to help differentiate pathology arising from the shoulder or the neck.

Spinal fusion surgery - the need to follow the 'BRAN' toolkit (benefits, risks, alternatives, nothing): a case report.

Failed back surgery syndrome is defined as increased or persistent pain following spinal surgery. Despite a relatively high incidence of failed back surgery syndrome (20%), patients may not be counselled regarding this complication pre-operatively. The Academy of Medical Royal Colleges has provided the Benefits, Risks, Alternatives and doing Nothing Toolkit to guide clinical discussions during the consent process.

Does orthotics use improve comfort, speed and injury rate during running? Preliminary analysis of a randomised control trial.

Background: Evidence regarding the effectiveness of using orthotics in improving comfort, increasing running speed and helping to reduce injury rate during running is limited and mixed. Alongside the increasing popularity of running is the increasing rate of running-related injuries (RRIs). Further research into whether orthotics could be used to help reduce RRIs would be highly beneficial for those affected.

Should iterative spinal surgeries be performed? A case report.

The number of spinal surgeries performed is increasing. Along with this comes an increase in iterative surgeries. Each surgery that a patient undergoes has an increased risk of complication and a decreased success rate compared to the last.

Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus.

Objectives: To elucidate the mechanism of action of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, and describe immunological pathways related to disease activity in adults with systemic lupus erythematosus (SLE) receiving standard background therapy in a phase II trial.

Methods: Patients with SLE were treated with baricitinib 2 mg or 4 mg in a phase II randomised, placebo-controlled study. Sera from 239 patients (baricitinib 2 mg: n=88; baricitinib 4 mg: n=82; placebo: n=69) and 49 healthy controls (HCs) were collected at baseline and week 12 and analysed using a proximity extension assay (Target 96 Inflammation Panel (Olink)).

Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab.

Background: A thorough understanding of a patient's inflammatory response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial to discerning the associated, underlying immunological processes and to the selection and implementation of treatment strategies. Defining peripheral blood biomarkers relevant to SARS-CoV-2 infection is fundamental to detecting and monitoring this systemic disease. This safety-focused study aims to monitor and characterize the immune response to SARS-CoV-2 infection via analysis of peripheral blood and nasopharyngeal swab samples obtained from patients hospitalized with Coronavirus disease 2019 (COVID-19), in the presence or absence of bamlanivimab treatment.

Predictive biomarker modeling of pediatric atopic dermatitis severity based on longitudinal serum collection.

The pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on atopic dermatitis diagnoses.

Transcriptomic Analysis of Healthy and Atopic Dermatitis Samples Reveals the Role of IL-37 in Human Skin.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects up to one in five children and millions of adults in developed countries. Clinically, AD skin lesions manifest as subacute and/or chronic lichenified eczematous plaques, which are often intensely pruritic and prone to secondary bacterial and viral infections. Despite the emergence of novel therapeutic agents, treatment options and outcomes for AD remain suboptimal.

Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate-to-severe disease.

Atopic dermatitis (AD) is a heterogeneous systemic inflammatory skin disease associated with dysregulated immune responses, barrier dysfunction and activated sensory nerves. To characterize circulating inflammatory profiles and underlying systemic disease heterogeneity within AD patients, blood samples from adult patients (N = 123) with moderate-to-severe AD in a phase 2 study of baricitinib (JAHG) were analysed. Baseline levels of 131 markers were evaluated using high-throughput and ultrasensitive proteomic platforms, patient clusters were generated based on these peripheral markers.

Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19.

Background: Physicians treating patients with coronavirus disease 2019 (COVID-19) increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across the spectrum of COVID-19 have not been characterized compared with healthy controls, but such analyses are likely to yield insights into the pursuit of interventions that adequately reduce the burden of these cytokine storms.

Objective: To identify and characterize the host inflammatory response to severe acute respiratory syndrome coronavirus 2 infection, we assessed levels of proteins related to immune responses and cardiovascular disease in patients stratified as mild, moderate, and severe versus matched healthy controls.

A Gα12-specific Binding Domain in AKAP-Lbc and p114RhoGEF.

AKAP-Lbc is a Rho-activating guanine nucleotide exchange factor (RhoGEF) important in heart development and pro-fibrotic signaling in cardiomyocytes. Heterotrimeric G proteins of the G12/13 subfamily, comprising Gα12 and Gα13, are well characterized as stimulating a specialized group of RhoGEFs through interaction with their RGS-homology (RH) domain. Despite lacking an RH domain, AKAP-Lbc is bound by Gα12 through an unknown mechanism to activate Rho signaling.

Imatinib reverses doxorubicin resistance by affecting activation of STAT3-dependent NF-κB and HSP27/p38/AKT pathways and by inhibiting ABCB1.

Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression.

Hippocampal magnetic resonance imaging abnormalities in cardiac arrest are associated with poor outcome.

Background: The role of neuroimaging in assessing prognosis in comatose cardiac survivors appears promising, but little is known regarding the import of particular spatial patterns. We report a specific spatial imaging abnormality on magnetic resonance imaging (MRI) that portends a poor prognosis: bilateral hippocampal hyperintensities on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences.

Methods: Eighty sequential comatose cardiac arrest patients underwent MRI scans.

Automated sample preparation for ICP analysis of active pharmaceutical ingredients and intermediates.

Routine testing of active pharmaceutical ingredients (APIs) for metal residues is an expectation of regulatory bodies such as the FDA (U.S. Food and Drug Administration).

Anaplasma phagocytophilum APH_0032 is expressed late during infection and localizes to the pathogen-occupied vacuolar membrane.

Anaplasma phagocytophilum infects neutrophils and myeloid, endothelial, and tick cell lines to reside within a host cell-derived vacuole that is indispensible for its survival. Here, we identify APH_0032 as an Anaplasma-derived protein that associates with the A. phagocytophilum-occupied vacuolar membrane (AVM).

Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer.

Targeting the estrogen receptor is an important strategy in breast cancer therapy. However, although inhibiting estrogen receptor function with specific estrogen receptor modulators can achieve a primary response in cancer patients, intrinsic or subsequently acquired resistance to the therapy remains a major obstacle in the clinic. Thus, it is critical to gain a more thorough understanding of how estrogen receptor functions are regulated in breast cancer.

Anaplasma phagocytophilum APH_1387 is expressed throughout bacterial intracellular development and localizes to the pathogen-occupied vacuolar membrane.

Obligate vacuolar pathogens produce proteins that localize to the host cell-derived membranes of the vacuoles in which they reside, yielding unique organelles that are optimally suited for pathogen survival. Anaplasma phagocytophilum is an obligate vacuolar bacterium that infects neutrophils and causes the emerging and potentially fatal disease human granulocytic anaplasmosis. Here we identified APH_1387 as the first A.