Missing in action: A bibliometric analysis of military research in the medical literature since 1950.

BACKGROUND: Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime. METHODS: We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's Chi Square and Mann-Whitney U test, with p < 0.05 considered a significant difference. RESULTS: From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range 1.5-3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce. CONCLUSION: There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap.

Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood-brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) - as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity - meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment-focused MRI-siRNA theranostics for the better treatment and diagnosis of medulloblastoma.

CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy.

PURPOSE: Although checkpoint inhibitors have improved first-line treatment for non-small cell lung cancer (NSCLC), a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti-PD-L1/PD-1 immunotherapy. CONTACT-01 (ClinicalTrials.gov identifier: NCT04471428) evaluated atezolizumab plus cabozantinib versus docetaxel in patients with metastatic NSCLC who developed disease progression after concurrent or sequential treatment with anti-PD-L1/PD-1 and platinum-containing chemotherapy. METHODS: This multicenter, open-label, phase III trial randomly assigned patients 1:1 to atezolizumab 1,200 mg intravenously once every 3 weeks (q3w) plus cabozantinib 40 mg orally once daily or docetaxel 75 mg/m2 intravenously once every 3 weeks. The primary end point was overall survival (OS). RESULTS: One hundred eighty-six patients were assigned atezolizumab plus cabozantinib, and 180 docetaxel. Minimum OS follow-up was 10.9 months. Median OS was 10.7 months (95% CI, 8.8 to 12.3) with atezolizumab plus cabozantinib and 10.5 months (95% CI, 8.6 to 13.0) with docetaxel (stratified hazard ratio [HR], 0.88 [95% CI, 0.68 to 1.16]; P = .3668). Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% CI, 0.59 to 0.92]). Serious adverse events (AEs) occurred in 71 (38.4%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 3/4 treatment-related AEs occurred in 73 (39.5%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 5 AEs occurred in 14 (7.6%) and 10 (6.0%) patients in the atezolizumab plus cabozantinib and docetaxel arms, respectively (treatment-related in four [2.2%] and one [0.6%], respectively). CONCLUSION: Atezolizumab plus cabozantinib after disease progression following anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve OS compared with docetaxel. Safety was consistent with known profiles of these agents.

Comparison of Clinical Decision Support Tools to Improve Pediatric Lipid Screening.

OBJECTIVE: To test whether different clinical decision support tools increase clinician orders and patient completions relative to standard practice and each other. STUDY DESIGN: A pragmatic, patient-randomized clinical trial in the electronic health record was conducted between October 2019 and April 2020 at Geisinger Health System in Pennsylvania, with 4 arms: care gap-a passive listing recommending screening; alert-a panel promoting and enabling lipid screen orders; both; and a standard practice-no guideline-based notification-control arm. Data were analyzed for 13 346 9- to 11-year-old patients seen within Geisinger primary care, cardiology, urgent care, or nutrition clinics, or who had an endocrinology visit. Principal outcomes were lipid screening orders by clinicians and completions by patients within 1 week of orders. RESULTS: Active (care gap and/or alert) vs control arm patients were significantly more likely (P < .05) to have lipid screening tests ordered and completed, with ORs ranging from 1.67 (95% CI 1.28-2.19) to 5.73 (95% CI 4.46-7.36) for orders and 1.54 (95% CI 1.04-2.27) to 2.90 (95% CI 2.02-4.15) for completions. Alerts, with or without care gaps listed, outperformed care gaps alone on orders, with odds ratios ranging from 2.92 (95% CI 2.32-3.66) to 3.43 (95% CI 2.73-4.29). CONCLUSIONS: Electronic alerts can increase lipid screening orders and completions, suggesting clinical decision support can improve guideline-concordant screening. The study also highlights electronic record-based patient randomization as a way to determine relative effectiveness of support tools. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04118348.

Exploring Peptido-Nanocomposites in the Context of Amyloid Diseases.

Therapeutic peptides are a major class of pharmaceutical drugs owing to their target-binding specificity as well as their versatility in inhibiting aberrant protein-protein interactions associated with human pathologies. Within the realm of amyloid diseases, the use of peptides and peptidomimetics tailor-designed to overcome amyloidogenesis has been an active research endeavor since the late 90s. In more recent years, incorporating nanoparticles for enhancing the biocirculation and delivery of peptide drugs has emerged as a frontier in nanomedicine, and nanoparticles have further demonstrated a potency against amyloid aggregation and cellular inflammation to rival strategies employing small molecules, peptides, and antibodies. Despite these efforts, however, a fundamental understanding of the chemistry, characteristics and function of peptido-nanocomposites is lacking, and a systematic analysis of such strategy for combating a range of amyloid pathogeneses is missing. Here we review the history, principles and evolving chemistry of constructing peptido-nanocomposites from bottom up and discuss their future application against amyloid diseases that debilitate a significant portion of the global population.

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. CLINICAL TRIALS REGISTRATION: NCT04047719.

Previous immune checkpoint inhibitor therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry.

OBJECTIVES: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. METHODS: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. RESULTS: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). CONCLUSION: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.

Length-Dependent Cellular Internalization of Nanobody-Functionalized Poly(2-oxazoline) Nanorods.

The ability to target specific tissues and to be internalized by cells is critical for successful nanoparticle-based targeted drug delivery. Here, we combined "stealthy" rod-shaped poly(2-oxazoline) (POx) nanoparticles of different lengths with a cancer marker targeting nanobody and a fluorescent cell internalization sensor via a heat-induced living crystallization-driven self-assembly (CDSA) strategy. A significant increase in association and uptake driven by nanobody-receptor interactions was observed alongside nanorod-length-dependent kinetics. Importantly, the incorporation of the internalization sensor allowed for quantitative differentiation between cell surface association and internalization of the targeted nanorods, revealing unprecedented length-dependent cellular interactions of CDSA nanorods. This study highlights the modularity and versatility of the heat-induced CDSA process and further demonstrates the potential of POx nanorods as a modular nanomedicine platform.

Multimodality local consolidative treatment versus conventional care of advanced lung cancer after first-line systemic anti-cancer treatment: study protocol for the RAMON multicentre randomised controlled trial with an internal pilot.

INTRODUCTION: Lung cancer is the most common cause of cancer death worldwide and most patients present with extensive disease. One-year survival is improving but remains low (37%) despite novel systemic anti-cancer treatments forming the current standard of care. Although new therapies improve survival, most patients have residual disease after treatment, and little is known on how best to manage it. Therefore, residual disease management varies across the UK, with some patients receiving only maintenance systemic anti-cancer treatment while others receive local consolidative treatment (LCT), alongside maintenance systemic anti-cancer treatment. LCT can be a combination of surgery, radiotherapy and/or ablation to remove all remaining cancer within the lung and throughout the body. This is intensive, expensive and impacts quality of life, but we do not know if it results in better survival, nor the extent of impact on quality of life and what the cost might be for healthcare providers. The RAMON study (RAdical Management Of Advanced Non-small cell lung cancer) will evaluate the acceptability, effectiveness and cost-effectiveness of LCT versus no LCT after first-line systemic treatment for advanced lung cancer. METHODS AND ANALYSIS: RAMON is a pragmatic open multicentre, parallel group, superiority randomised controlled trial. We aim to recruit 244 patients aged 18 years and over with advanced non-small-cell lung cancer from 40 UK NHS hospitals. Participants will be randomised in a 1:1 ratio to receive LCT alongside maintenance treatment, or maintenance treatment alone. LCT will be tailored to each patient's specific disease sites. Participants will be followed up for a minimum of 2 years. The primary outcome is overall survival from randomisation. ETHICS AND DISSEMINATION: The West of Scotland Research Ethics Committee (22/WS/0121) gave ethical approval in August 2022 and the Health Research Authority in September 2022. Participants will provide written informed consent before participating in the study. Findings will be presented at international meetings, in peer-reviewed publications, through patient organisations and notifications to patients. TRIAL REGISTRATION NUMBER: ISRCTN11613852.

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3-6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable. Here we present the discovery and characterization of ABBV-CLS-484 (AC484), a first-in-class, orally bioavailable, potent PTPN2 and PTPN1 active-site inhibitor. AC484 treatment in vitro amplifies the response to interferon and promotes the activation and function of several immune cell subsets. In mouse models of cancer resistant to PD-1 blockade, AC484 monotherapy generates potent anti-tumour immunity. We show that AC484 inflames the tumour microenvironment and promotes natural killer cell and CD8+ T cell function by enhancing JAK-STAT signalling and reducing T cell dysfunction. Inhibitors of PTPN2 and PTPN1 offer a promising new strategy for cancer immunotherapy and are currently being evaluated in patients with advanced solid tumours (ClinicalTrials.gov identifier NCT04777994 ). More broadly, our study shows that small-molecule inhibitors of key intracellular immune regulators can achieve efficacy comparable to or exceeding that of antibody-based immune checkpoint blockade in preclinical models. Finally, to our knowledge, AC484 represents the first active-site phosphatase inhibitor to enter clinical evaluation for cancer immunotherapy and may pave the way for additional therapeutics that target this important class of enzymes.

Oatp (Organic Anion Transporting Polypeptide)-Mediated Transport: A Mechanism for Atorvastatin Neuroprotection in Stroke.

BACKGROUND: Drug discovery for stroke is challenging as indicated by poor clinical translatability. In contrast, HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (ie, statins) improve poststroke neurological outcomes. This property requires transport across the blood-brain barrier via an endogenous uptake transporter (ie, Oatp1a4 [organic anion transporting polypeptide 1a4]). Our goal was to study Oatp1a4 as a drug delivery mechanism because the blood-brain barrier cannot be assumed to be completely open for all drugs in ischemic stroke. METHODS: Male Sprague-Dawley rats (200-250 g) were subjected to middle cerebral artery occlusion (90 minutes) followed by reperfusion for up to 7 days. Atorvastatin (20 mg/kg, IV) was administered 2 hours following intraluminal suture removal. Involvement of Oatp-mediated transport was determined using fexofenadine (3.2 mg/kg, IV), a competitive Oatp inhibitor. Oatp1a4 transport activity was measured by in situ brain perfusion. Infarction volumes/brain edema ratios and neuronal nuclei expression were determined using 2,3,5-triphenyltetrazolium chloride-stained brain tissue slices and confocal microscopy, respectively. Poststroke functional outcomes were assessed via neurological deficit scores and rotarod analysis. RESULTS: At 2-hour post-middle cerebral artery occlusion, [3H]atorvastatin uptake was increased in ischemic brain tissue. A single dose of atorvastatin significantly reduced post-middle cerebral artery occlusion infarction volume, decreased brain edema ratio, increased caudoputamen neuronal nuclei expression, and improved functional neurological outcomes. All middle cerebral artery occlusion positive effects of atorvastatin were attenuated by fexofenadine coadministration (ie, an Oatp transport inhibitor). CONCLUSIONS: Our data demonstrate that neuroprotective effects of atorvastatin may require central nervous system delivery by Oatp-mediated transport at the blood-brain barrier, a mechanism that persists despite increased cerebrovascular permeability in ischemic stroke. These novel and translational findings support utility of blood-brain barrier transporters in drug delivery for neuroprotective agents.

Alzheimer's Progenitor Amyloid-ß Targets and Dissolves Microbial Amyloids and Impairs Biofilm Function.

Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-ß (Aß) is a pathological hallmark. However, Aß peptide is also observed in the intestinal tissues of AD patients and animal models. In this study, it is reported that Aß monomers can target and disintegrate microbial amyloids of FapC and CsgA formed by opportunistic gut pathogens, Pseudomonas aeruginosa and Escherichia coli, explaining a potential role of Aß in the gut-brain axis. Employing a zebrafish-based transparent in vivo system and whole-mount live-imaging, Aß is observed to diffuse into the vasculature and subsequently localize with FapC or CsgA fibrils that were injected into the tail muscles of the fish. FapC aggregates, produced after Aß treatment (Faß), present selective toxicity to SH-SY5Y neuronal cells while the intestinal Caco-2 cells are shown to phagocytose Faß in a non-toxic cellular process. After remodeling by Aß, microbial fibrils lose their native function of cell adhesion with intestinal Caco-2 cells and Aß dissolves and detaches the microbial fibrils already attached to the cell membrane. Taken together, this study strongly indicates an anti-biofilm role for Aß monomers that can help aid in the future development of selective anti-Alzheimer's and anti-infective medicine.

Chronic Granulomatous Reaction to Semi-permanent Eyebrow Tint.

Eyebrow micropigmentation, also known as eyebrow microblading or embroidery, is a new technique in the field of semi-permanent cosmetics that are used for therapeutic and aesthetic purposes to recreate eyebrow structure and definition. It uses synthetic pigment that is deposited through fine needles into the papillary dermis and remains till the body metabolizes the pigment and clinically fades away by 12-18 months. Similar to other tattooing procedures, microblading involves risks including local inflammation, infection, allergic contact dermatitis, and granulomatous reactions that can occur from months to years after the procedure. We describe herein a case of a 49-year-old female who has persistent erythematous and indurated plaques on both eyebrows after a microblading procedure performed over a year and a half prior to her initial visit.

Understanding the behavioral determinants that predict barriers and enablers of screening and treatment behaviors for diabetic retinopathy among Bangladeshi women: findings from a barrier analysis.

BACKGROUND AND AIM: While early detection and timely treatments can prevent diabetic retinopathy (DR) related blindness, barriers to receiving these DR services may cause permanent sight loss. Despite having similar prevalence to diabetes and DR, women are less likely than men to perform these behaviors due to multi-faced barriers in screening and receiving follow-up treatments for DR. This study, therefore, aimed at identifying the barriers to - and enablers of - screening and follow-up treatments behaviors for DR among women aged more than 40 years with diabetes from the behavioral perspectives in Bangladesh. METHODS: This Barrier Analysis study interviewed 360 women (180 "Doers" and 180 "Non-doers") to explore twelve behavioral determinants of four DR behaviors including screening, injection of anti-vascular endothelial growth factor (anti-VEGF medication), laser therapy and vitro-retinal surgery. The data analysis was performed to calculate estimated relative risk to identify the degree of association between the determinants and behaviors, and to find statistically significant differences (at p < 0.05) in the responses between the Doers and Non-doers. RESULTS: Access to healthcare facilities was the major barrier impeding women from performing DR behaviors. Difficulty in locating DR service centers, the need to travel long distances, the inability to travel alone and during illness, challenges of paying for transportation and managing workload significantly affected women's ability to perform the behaviors. Other determinants included women's perceived self-efficacy, perceived negative consequences (e.g. fear and discomfort associated with injections or laser treatment), and cues for action. Significant perceived enablers included low cost of DR treatments, supportive attitudes by healthcare providers, government policy, and perceived social norms. CONCLUSION: The study found a host of determinants related to the barriers to and enablers of DR screening and treatment behaviors. These determinants included perceived self-efficacy (and agency), positive and negative consequences, perceived access, perceived social norms, culture, and perceived risk. Further investments are required to enhance the availability of DR services within primary and secondary health institutions along with health behavior promotion to dispel misconceptions and fears related to DR treatments.

The Northeastern Society of Plastic Surgeons: The First 40 Years.

ABSTRACT: The concept for creating the Northeastern Society of Plastic Surgeons originated in May 1982, at the American Association of Plastic Surgeons in Colorado Springs Colorado. The new society would supplement, not supplant, existing state and small regional societies. Two hundred fifty-seven northeastern plastic surgeons joined the charter membership. The inaugural meeting of the Northeastern Society of Plastic Surgeons was held in Philadelphia, September 1984. The following historical account highlights our society's founding principles and leadership throughout the first 40 years.

Systemic inflammation induced from remote extremity trauma is a critical driver of secondary brain injury.

Blast exposure, commonly experienced by military personnel, can cause devastating life-threatening polysystem trauma. Despite considerable research efforts, the impact of the systemic inflammatory response after major trauma on secondary brain injury-inflammation is largely unknown. The aim of this study was to identify markers underlying the susceptibility and early onset of neuroinflammation in three rat trauma models: (1) blast overpressure exposure (BOP), (2) complex extremity trauma (CET) involving femur fracture, crush injury, tourniquet-induced ischemia, and transfemoral amputation through the fracture site, and (3) BOP+CET. Six hours post-injury, intact brains were harvested and dissected to obtain biopsies from the prefrontal cortex, striatum, neocortex, hippocampus, amygdala, thalamus, hypothalamus, and cerebellum. Custom low-density microarray datasets were used to identify, interpret and visualize genes significant (p < 0.05 for differential expression [DEGs]; 86 neuroinflammation-associated) using a custom python-based computer program, principal component analysis, heatmaps and volcano plots. Gene set and pathway enrichment analyses of the DEGs was performed using R and STRING for protein-protein interaction (PPI) to identify and explore key genes and signaling networks. Transcript profiles were similar across all regions in naïve brains with similar expression levels involving neurotransmission and transcription functions and undetectable to low-levels of inflammation-related mediators. Trauma-induced neuroinflammation across all anatomical brain regions correlated with injury severity (BOP+CET > CET > BOP). The most pronounced differences in neuroinflammatory-neurodegenerative gene regulation were between blast-associated trauma (BOP, BOP+CET) and CET. Following BOP, there were few DEGs detected amongst all 8 brain regions, most were related to cytokines/chemokines and chemokine receptors, where PPI analysis revealed Il1b as a potential central hub gene. In contrast, CET led to a more excessive and diverse pro-neuroinflammatory reaction in which Il6 was identified as the central hub gene. Analysis of the of the BOP+CET dataset, revealed a more global heightened response (Cxcr2, Il1b, and Il6) as well as the expression of additional functional regulatory networks/hub genes (Ccl2, Ccl3, and Ccl4) which are known to play a critical role in the rapid recruitment and activation of immune cells via chemokine/cytokine signaling. These findings provide a foundation for discerning pathophysiological consequences of acute extremity injury and systemic inflammation following various forms of trauma in the brain.

Angiolymphoid Hyperplasia of the Orbit: A Rare Case Report and Review of the Literature.

Background: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular tumour of the skin which mainly involves the head and neck regions. Case Report: A 41 year old male presented to the ENT outpatient department with a swelling in the anterosuperomedial aspect of right orbital rim since two year. Following a contrast enhanced CT of the Head, complete surgical excision was done and diagnosis of ALHE was confirmed by histopathology. Methodology: We performed a systematic review of the literature following the preferred reporting items for Systematic reviews. Literature searches were conducted in web based search engines using MeSH terms and key words. We found seven publications that fit the inclusion criteria which included case reports and case series. Conclusion: ALHE involving the orbit has been very rarely reported and is a challenging diagnosis. Complete surgical excision is the treatment of choice and recurrence can occur with incomplete removal.

Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.

Brain pathologies are considered one of the greatest contributors of death and disability worldwide. Neurodegenerative Alzheimer's disease is the second leading cause of death in adults, whilst brain cancers including glioblastoma multiforme in adults, and pediatric-type high-grade gliomas in children remain largely untreatable. A further compounding issue for patients with brain pathologies is that of long-term neuropsychiatric sequela - as a symptom or arising from high dose therapeutic intervention. The major challenge to effective, low dose treatment is finding therapeutics that successfully cross the blood-brain barrier and target aberrant cellular processes, while having minimum effect on essential cellular processes, and healthy bystander cells. Following over 30 years of research, CRISPR technology has emerged as a biomedical tour de force with the potential to revolutionise the treatment of both neurological and cancer related brain pathologies. The aim of this review is to take stock of the progress made in CRISPR technology in relation to treating brain pathologies. Specifically, we will describe studies which look beyond design, synthesis, and theoretical application; and focus instead on in vivo studies with translation potential. Along with discussing the latest breakthrough techniques being applied within the CRISPR field, we aim to provide a prospective on the knowledge gaps that exist and challenges that still lay ahead for CRISPR technology prior to successful application in the brain disease treatment field.

Multiple Flesh-Colored Nodules: A Patient with Multiple BAP 1-Inactivated Melanocytic Tumors.

A 22-year-old man without previously known skin disease presented with multiple asymptomatic, skin-brown to red-brown papules on the head and neck for 1 year (Figure 1). The diagnoses considered included benign intradermal or compound nevi, atypical nevi, and neurofibromas. Shave biopsies of three lesions revealed intradermal melanocytic lesions comprising large epithelioid melanocytes flanked by small banal melanocytes (Figure 2). All nevi had a low proliferation index, absent junctional component as demonstrated by a dual Ki-67/Mart-1 immunostain, and no dermal mitotic figures. Immunostaining demonstrated lesional melanocytes positive for p16, but the larger epithelioid melanocytes in these lesions lacked nuclear expression of ubiquitin carboxyl-terminal hydrolase protein (BAP-1; Figure 3). The diagnosis of a BAP-1-inactivated nevus was made, and the patient was referred for genetic counseling and screening for associated malignancies. Given that the lesions involved deep margins, the same were completely excised.