Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community

Smart Moves: Effects of Relative Brain Size on Establishment Success of Invasive Amphibians and Reptiles

Brain size relative to body size varies considerably among animals, but the ecological consequences of that variation remain poorly understood. Plausibly, larger brains confer increased behavioural flexibility, and an ability to respond to novel challenges. In keeping with that hypothesis, successful invasive species of birds and mammals that flourish after translocation to a new area tend to have larger brains than do unsuccessful invaders. We found the same pattern in ectothermic terrestrial vertebrates. Brain size relative to body size was larger in species of amphibians and reptiles reported to be successful invaders, compared to species that failed to thrive after translocation to new sites. This pattern was found in six of seven global biogeographic realms; the exception (where relatively larger brains did not facilitate invasion success) was Australasia. Establishment success was also higher in amphibian and reptile families with larger relative brain sizes. Future work could usefully explore whether invasion success is differentially associated with enlargement of specific parts of the brain (as predicted by the functional role of the forebrain in promoting behavioural flexibility), or with a general size increase (suggesting that invasion success is facilitated by enhanced perceptual and motor skills, as well as cognitive ability)

Circulating sCD14 Is Associated with Virological Response to Pegylated-Interferon-Alpha/Ribavirin Treatment in HIV/HCV Co-Infected Patients

Microbial translocation (MT) through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10) reduction from baseline after 12 weeks of therapy) and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014).In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy

Healthy people with nature in mind

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: The global disease burden resulting from climate change is likely to be substantial and will put further strain on public health systems that are already struggling to cope with demand. An up- stream solution, that of preventing climate change and associated adverse health effects, is a promising approach, which would create win-win-situations where both the environment and human health benefit. One such solution would be to apply methods of behaviour change to prompt pro-environmentalism, which in turn benefits health and wellbeing. DISCUSSION: Based on evidence from the behavioural sciences, we suggest that, like many social behaviours, pro- environmental behaviour can be automatically induced by internal or external stimuli. A potential trigger for such automatic pro-environmental behaviour would be natural environments themselves. Previous research has demonstrated that natural environments evoke specific psychological and physiological reactions, as demonstrated by self-reports, epidemiological studies, brain imaging techniques, and various biomarkers. This suggests that exposure to natural environments could have automatic behavioural effects, potentially in a pro-environmental direction, mediated by physiological reactions. Providing access and fostering exposure to natural environments could then serve as a public health tool, together with other measures, by mitigating climate change and achieving sustainable health in sustainable ecosystems. However, before such actions are implemented basic research is required to elucidate the mechanisms involved, and applied investigations are needed to explore real world impacts and effect magnitudes. As environmental research is still not sufficiently integrated within medical or public health studies there is an urgent need to promote interdisciplinary methods and investigations in this critical field. Health risks posed by anthropogenic climate change are large, unevenly distributed, and unpredictable. To ameliorate negative impacts, pro-environmental behaviours should be fostered. Potentially this could be achieved automatically through exposure to favourable natural environments, with an opportunity for cost-efficient nature-based solutions that provide benefits for both the environment and public health

Characterising within-hospital SARS-CoV-2 transmission events using epidemiological and viral genomic data across two pandemic waves

Hospital outbreaks of COVID19 result in considerable mortality and disruption to healthcare services and yet little is known about transmission within this setting. We characterise within hospital transmission by combining viral genomic and epidemiological data using Bayesian modelling amongst 2181 patients and healthcare workers from a large UK NHS Trust. Transmission events were compared between Wave 1 (1st March to 25th July 2020) and Wave 2 (30th November 2020 to 24th January 2021). We show that staff-to-staff transmissions reduced from 31.6% to 12.9% of all infections. Patient-to-patient transmissions increased from 27.1% to 52.1%. 40%-50% of hospital-onset patient cases resulted in onward transmission compared to 4% of community-acquired cases. Control measures introduced during the pandemic likely reduced transmissions between healthcare workers but were insufficient to prevent increasing numbers of patient-to-patient transmissions. As hospital-acquired cases drive most onward transmission, earlier identification of nosocomial cases will be required to break hospital transmission chains

What Factors Are Predictive of Outcome in the Treatment of Soft Tissue Sarcomas of the Foot and Ankle?

Category: Tumor Introduction/Purpose: Soft tissue sarcomas (STS) of the foot and ankle are common, accounting for 10% of sarcomas; however, there exists little published data on the outcome of treatment. Because of the unique anatomy of the foot and ankle, and the fact that benign lesions in this area are 200-fold more common than malignant lesions, these tumors can be frequently misdiagnosed, leading to unplanned excision and poor outcomes. The purpose of this study was to describe outcomes of the surgical treatment of STS of the foot and ankle at our institution, with an analysis on risk factors for local and distant recurrence, as well as overall survival. Methods: We reviewed the records of 62 foot and ankle soft tissue sarcomas treated with definitive surgery at our institution between 1992 and 2013. The cohort consisted of 35 males and 27 females with a mean age at diagnosis of 45 years and a mean follow-up of 7 years. Age, gender, anatomic location, tumor size, subtype, stage, neoadjuvant and adjuvant treatments, previous surgery, surgical procedure, and disease status at latest follow-up was recorded. Results: The most common tumor subtype was synovial sarcoma (n = 16). The overall limb salvage rate was 53%. Local recurrence was observed in 9 patients and distant metastases in 15 patients. Tumor size >=3 cm in maximal dimension was the greatest risk factor in mortality. Post treatment complications occurred in 15 patients. Local recurrence and development of distant disease was relatively common following wide excision of a soft tissue sarcoma of the foot and ankle. Tumors that were >=3 cm in maximal dimension were associated with a worse overall survival and patients with neoadjuvant radiation were at increased risk of complications. Conclusion: The results of our study highlight the aggressive nature of soft tissue sarcomas of the foot and ankle, with smaller tumors than previously reported (<5 cm) behaving like high-grade advanced disease

Laceration of the Sciatic Nerve After Closed Reduction of a Dislocated Total Hip Arthroplasty

Sciatic nerve injury after closed reduction of a dislocated total hip arthroplasty (THA) is an exceedingly rare but tremendously devastating complication. Closed reduction is the standard of care and is typically associated with a low complication rate. There have only been seven sciatic nerve injuries after closed reduction of a dislocated THA reported in the literature, and none were secondary to nerve laceration. We report a case of sciatic nerve laceration after attempted closed reduction of a dislocated THA. This resulted in complete loss of sensory and motor sciatic nerve function. This case highlights the importance of a detailed neurologic examination before and after closed reduction of a dislocated total hip, the importance of using careful reduction maneuvers, and transitioning to open reduction when necessary

The use of deep learning in medical imaging to improve spine care: A scoping review of current literature and clinical applications

Background: Artificial intelligence is a revolutionary technology that promises to assist clinicians in improving patient care. In radiology, deep learning (DL) is widely used in clinical decision aids due to its ability to analyze complex patterns and images. It allows for rapid, enhanced data, and imaging analysis, from diagnosis to outcome prediction. The purpose of this study was to evaluate the current literature and clinical utilization of DL in spine imaging. Methods: This study is a scoping review and utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to review the scientific literature from 2012 to 2021. A search in PubMed, Web of Science, Embased, and IEEE Xplore databases with syntax specific for DL and medical imaging in spine care applications was conducted to collect all original publications on the subject. Specific data was extracted from the available literature, including algorithm application, algorithms tested, database type and size, algorithm training method, and outcome of interest. Results: A total of 365 studies (total sample of 232,394 patients) were included and grouped into 4 general applications: diagnostic tools, clinical decision support tools, automated clinical/instrumentation assessment, and clinical outcome prediction. Notable disparities exist in the selected algorithms and the training across multiple disparate databases. The most frequently used algorithms were U-Net and ResNet. A DL model was developed and validated in 92% of included studies, while a pre-existing DL model was investigated in 8%. Of all developed models, only 15% of them have been externally validated. Conclusions: Based on this scoping review, DL in spine imaging is used in a broad range of clinical applications, particularly for diagnosing spinal conditions. There is a wide variety of DL algorithms, database characteristics, and training methods. Future studies should focus on external validation of existing models before bringing them into clinical use