Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs.

Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium.

Iliac crest bone graft versus cell-based grafts to augment spinal fusion: a systematic review and meta-analysis.

Introduction: Despite successful fusion rates with iliac crest bone graft (ICBG), donor-site morbidity and increased operating time remain a considerable limitation and drive the search for alternatives. In this systematic review, grafts with additional cellular supplementation were compared with ICBG for spinal arthrodesis. We compared safety, efficacy and long-term outcomes, thus providing the current and relevant evidence for orthopaedic surgeons to make informed choices regarding this rapidly developing field.

Digitally Assisted Peer Recovery Coach to Facilitate Linkage to Outpatient Treatment Following Inpatient Alcohol Withdrawal Treatment: Proof-of-Concept Pilot Study.

Background: Alcohol use disorder (AUD), associated with significant morbidity and mortality, continues to be a major public health problem. The COVID-19 pandemic exacerbated the impact of AUD, with a 25% increase in alcohol-related mortality from 2019 to 2020. Thus, innovative treatments for AUD are urgently needed.

Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network.

Modeling the developmental etiology of viable human aneuploidy can be challenging in rodents due to syntenic boundaries, or primate-specific biology. In humans, monosomy-X (45,X) causes Turner syndrome (TS), altering craniofacial, skeletal, endocrine, and cardiovascular development, which in contrast remain unaffected in 39,X-mice. To learn how human monosomy-X may impact early embryonic development, we turned to human 45,X and isogenic euploid induced pluripotent stem cells (hiPSCs) from male and female mosaic donors.

Altered T cell infiltration and enrichment of leukocyte regulating pathways within aged skeletal muscle are associated impaired muscle function following influenza infection.

Older adults have diminished immune responses that increase susceptibility to infectious diseases, such as influenza (flu). In older adults, flu infection can lead to hospitalization, catastrophic disability, and mortality. We previously demonstrated severe and prolonged muscle degradation and atrophy in aged mice during flu infection.

Risk factors for distal junctional failure in long-construct instrumentation for adult spinal deformity.

Purpose: The aim of this study is to identify risk factors associated with postoperative DJF in long constructs for ASD.

Methods: A retrospective review was performed at a tertiary referral spine centre from 01/01/2007 to 31/12/2016. Demographic, clinical and radiographic parameters were collated for patients with DJF in the postoperative period and compared to those without DJF.

Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta.

Mammalian sex chromosomes encode homologous X/Y gene pairs that were retained on the Y chromosome in males and escape X chromosome inactivation (XCI) in females. Inferred to reflect X/Y pair dosage sensitivity, monosomy X is a leading cause of miscarriage in humans with near full penetrance. This phenotype is shared with many other mammals but not the mouse, which offers sophisticated genetic tools to generate sex chromosomal aneuploidy but also tolerates its developmental impact.

Pharmacogenetic profiling and individualised therapy in the treatment of degenerative spinal conditions.

Patients presenting with degenerative spinal changes are often poor surgical candidates due to associated co-morbidities, frailty, or sarcopenia. Additionally, surgeries of a degenerative spine can prove difficult due to the distortion of normal surgical anatomy. Therefore, many patients are managed conservatively with a variety of modalities, including over-the-counter and prescription medications.

Scaffold microarchitecture regulates angiogenesis and the regeneration of large bone defects.

Emerging 3D printing technologies can provide exquisite control over the external shape and internal architecture of scaffolds and tissue engineering (TE) constructs, enabling systematic studies to explore how geometric design features influence the regenerative process. Here we used fused deposition modelling (FDM) and melt electrowriting (MEW) to investigate how scaffold microarchitecture influences the healing of large bone defects. FDM was used to fabricate scaffolds with relatively large fibre diameters and low porosities, while MEW was used to fabricate scaffolds with smaller fibre diameters and higher porosities, with both scaffolds being designed to have comparable surface areas.

The relationship between radiological paraspinal lumbar measures and clinical measures of sarcopenia in older patients with chronic lower back pain.

Objectives: Sarcopenia is postulated to be an influential factor in chronic low back pain. The aim of this study is to evaluate the relationship between traditional clinical measures of sarcopenia and novel radiographic methods which evaluate overall muscle status, such as adjusted psoas cross-sectional area (APCSA) and degree of fat infiltration (%FI) in paraspinal muscles, in patients with chronic low back pain.

Methods: Prospective study performed at our institution from 01/01/19-01/04/19.

Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.

Aims: CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms.

Designing a Framework for Remote Cancer Care Through Community Co-design: Participatory Development Study.

Background: Recent shifts to telemedicine and remote patient monitoring demonstrate the potential for new technology to transform health systems; yet, methods to design for inclusion and resilience are lacking.

Objective: The aim of this study is to design and implement a participatory framework to produce effective health care solutions through co-design with diverse stakeholders.

Methods: We developed a design framework to cocreate solutions to locally prioritized health and communication problems focused on cancer care.

Bilayered extracellular matrix derived scaffolds with anisotropic pore architecture guide tissue organization during osteochondral defect repair.

While some clinical advances in cartilage repair have occurred, osteochondral (OC) defect repair remains a significant challenge, with current scaffold-based approaches failing to recapitulate the complex, hierarchical structure of native articular cartilage (AC). To address this need, we fabricated bilayered extracellular matrix (ECM)-derived scaffolds with aligned pore architectures. By modifying the freeze-drying kinetics and controlling the direction of heat transfer during freezing, it was possible to produce anisotropic scaffolds with larger pores which supported homogenous cellular infiltration and improved sulfated glycosaminoglycan deposition.

Preoperative Considerations for the Frail Patient.

Frailty is a common geriatric syndrome, the relevance of which is becoming increasingly apparent in the clinical setting. It is often accompanied by varying degrees of sarcopenia and/or osteoporosis, leading to a decline in physical function, decreased levels of physical activity, and overall poorer health outcomes in older adults. Identifying this cohort of patients before stressor events such as spinal surgery can prove paramount to improving the postoperative outcomes of these patients.

Emerging digital technologies in cancer treatment, prevention, and control.

The very first issue of the journal of Translational Behavioral Medicine (TBM) was dedicated, in part, to the theme of Health Information Technology as a platform for evidence implementation. The topic was timely: legislation in the USA was passed with the intent of stimulating the adoption of electronic health records; mobile smartphones, tablets, and other devices were gaining traction in the consumer market, while members within the Society of Behavioral Medicine were gaining scientific understanding on how to use these tools to effect healthy behavior change. For the anniversary issue of TBM, we evaluated the progress and problems associated with deploying digital health technologies to support cancer treatment, prevention, and control over the last decade.

Differential Treatment Response Between Hypochondriasis With and Without Prominent Somatic Symptoms.

Health anxiety may exist with or without prominent somatic symptoms, but the impact of somatic symptoms on treatment response is unclear. The study objective was to examine this question further as symptom burden may impact choice of type of treatment. This exploratory study used a unique database from a prior trial of 193 individuals with DSM-IV hypochondriasis who had been randomly assigned to either cognitive behavioral therapy, fluoxetine, combined therapy, or placebo.

Changing Demographic Trends in spine trauma: The presentation and outcome of Major Spine Trauma in the elderly.

Introduction: Major trauma has seen a demographic shift in recent years and it is expected that the elderly population will comprise a greater burden on the major trauma service in the near future. However, whether a similar trend exists in those undergoing operative intervention for spinal trauma remains to be elucidated.

Aims: To compare the presentation and outcomes of patients ≥65 years of age sustaining spine trauma to those <65 years at a national tertiary referral spine centre.

Metabolic requirements of NK cells during the acute response against retroviral infection.

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity.

The diagnostic and prognostic value of artificial intelligence and artificial neural networks in spinal surgery : a narrative review.

In recent years, machine learning (ML) and artificial neural networks (ANNs), a particular subset of ML, have been adopted by various areas of healthcare. A number of diagnostic and prognostic algorithms have been designed and implemented across a range of orthopaedic sub-specialties to date, with many positive results. However, the methodology of many of these studies is flawed, and few compare the use of ML with the current approach in clinical practice.