Predictors of In-Hospital Mortality and Home Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A 4-Year Retrospective Analysis.

BACKGROUND: Factors associated with discharge disposition and mortality following aneurysmal subarachnoid hemorrhage (aSAH) are not well-characterized. We used a national all-payer database to identify factors associated with home discharge and in-hospital mortality. METHODS: The National Inpatient Sample was queried for patients with aSAH within a 4-year range. Weighted multivariable logistic regression models were constructed and adjusted for age, sex, race, household income, insurance status, comorbidity burden, National Inpatient Sample SAH Severity Score, disease severity, treatment modality, in-hospital complications, and hospital characteristics (size, teaching status, and region). RESULTS: Our sample included 37,965 patients: 33,605 were discharged alive and 14,350 were discharged home. Black patients had lower odds of in-hospital mortality compared with White patients (adjusted odds ratio [aOR] = 0.67, 95% confidence interval [CI] 0.52-0.86, p = 0.002). Compared with patients with private insurance, those with Medicare were less likely to have a home discharge (aOR = 0.58, 95% CI 0.46-0.74, p < 0.001), whereas those with self-pay (aOR = 2.97, 95% CI 2.29-3.86, p < 0.001) and no charge (aOR = 3.21, 95% CI 1.57-6.55, p = 0.001) were more likely to have a home discharge. Household income percentile was not associated with discharge disposition or in-hospital mortality. Paradoxically, increased number of Elixhauser comorbidities was associated with significantly lower odds of in-hospital mortality. CONCLUSIONS: We demonstrate independent associations with hospital characteristics, patient characteristics, and treatment characteristics as related to discharge disposition and in-hospital mortality following aSAH, adjusted for disease severity.

Functional genomics of abiotic environmental adaptation in lacertid lizards and other vertebrates.

Understanding the genomic basis of adaptation to different abiotic environments is important in the context of climate change and resulting short-term environmental fluctuations. Using functional and comparative genomics approaches, we here investigated whether signatures of genomic adaptation to a set of environmental parameters are concentrated in specific subsets of genes and functions in lacertid lizards and other vertebrates. We first identify 200 genes with signatures of positive diversifying selection from transcriptomes of 24 species of lacertid lizards and demonstrate their involvement in physiological and morphological adaptations to climate. To understand how functionally similar these genes are to previously predicted candidate functions for climate adaptation and to compare them with other vertebrate species, we then performed a meta-analysis of 1,100 genes under selection obtained from -omics studies in vertebrate species adapted to different abiotic factors. We found that the vertebrate gene set formed a tightly connected interactome, which was to 23% enriched in previously predicted functions of adaptation to climate, and to a large part (18%) involved in organismal stress response. We found a much higher degree of identical genes being repeatedly selected among different animal groups (43.6%), and of functional similarity and post-translational modifications than expected by chance, and no clear functional division between genes used for ectotherm and endotherm physiological strategies. In total, 171 out of 200 genes of Lacertidae were part of this network. These results highlight an important role of a comparatively small set of genes and their functions in environmental adaptation and narrow the set of candidate pathways and markers to be used in future research on adaptation and stress response related to climate change.

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.

PURPOSE: Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. METHODS: Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. RESULTS: We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. CONCLUSION: Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes.

Point-of-Care Ultrasound in the Evaluation of the Acutely Painful Red Eye.

BACKGROUND: Visual loss, ocular pain, and red eye are common presentations to front-line physicians in the emergency department, urgent care centers, or the primary care office. In recent decades, point-of-care ultrasound (POCUS) has been used by clinicians at the bedside in the evaluation and management of a vast array of patients, including those with ocular complaints. CASE REPORT: A 33-year-old man presented to the emergency department with left eye pain for 4 weeks' duration. The physical examination revealed visual acuity of 20/400 in the affected eye and diffuse conjunctival injection with perilimbal sparing and scleral edema. Using POCUS, he was noted to have diffuse thickening of the globe wall in the symptomatic eye with a thin layer of fluid posterior to the globe in Tenon's space and mild enlargement of the optic nerve sheath diameter. He was ultimately diagnosed with posterior scleritis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Posterior scleritis carries the potential for significant visual impairment when the diagnosis is missed or delayed. POCUS findings can aid the front-line physician in making the diagnosis of posterior scleritis allowing earlier initiation of appropriate therapy and follow-up.

Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2.

The RV144 trial demonstrated 31% vaccine efficacy at preventing human immunodeficiency virus (HIV)-1 infection. Antibodies against the HIV-1 envelope variable loops 1 and 2 (Env V1 and V2) correlated inversely with infection risk. We proposed that vaccine-induced immune responses against V1/V2 would have a selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P = 0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at position 181 was 78% (confidence interval 35% to 93%; P = 0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signature sites (21 ± 7 Å) and their match/mismatch dichotomy indicate that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high V1/V2-binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence that vaccine-induced V2 responses plausibly had a role in the partial protection conferred by the RV144 regimen.

Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

UNLABELLED: The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region. We explored the hypothesis that the genetic signatures in V1 and V2 could be partly attributed to selection by vaccine-primed T cells. We performed a T-cell-based sieve analysis of breakthrough viruses in the RV144 trial and found evidence of predicted HLA binding escape that was greater in vaccine versus placebo recipients. The predicted escape depended on class I HLA A*02- and A*11-restricted epitopes in the MN strain rgp120 vaccine immunogen. Though we hypothesized that this was indicative of postacquisition selection pressure, we also found that vaccine efficacy (VE) was greater in A*02-positive (A*02(+)) participants than in A*02(-) participants (VE = 54% versus 3%, P = 0.05). Vaccine efficacy against viruses with a lysine residue at site 169, important to antibody binding and implicated in vaccine-induced immune pressure, was also greater in A*02(+) participants (VE = 74% versus 15%, P = 0.02). Additionally, a reanalysis of vaccine-induced immune responses that focused on those that were shown to correlate with infection risk suggested that the humoral responses may have differed in A*02(+) participants. These exploratory and hypothesis-generating analyses indicate there may be an association between a class I HLA allele and vaccine efficacy, highlighting the importance of considering HLA alleles and host immune genetics in HIV vaccine trials. IMPORTANCE: The RV144 trial was the first to show efficacy against HIV-1 infection. Subsequently, much effort has been directed toward understanding the mechanisms of protection. Here, we conducted a T-cell-based sieve analysis, which compared the genetic sequences of viruses isolated from infected vaccine and placebo recipients. Though we hypothesized that the observed sieve effect indicated postacquisition T-cell selection, we also found that vaccine efficacy was greater for participants who expressed HLA A*02, an allele implicated in the sieve analysis. Though HLA alleles have been associated with disease progression and viral load in HIV-1 infection, these data are the first to suggest the association of a class I HLA allele and vaccine efficacy. While these statistical analyses do not provide mechanistic evidence of protection in RV144, they generate testable hypotheses for the HIV vaccine community and they highlight the importance of assessing the impact of host immune genetics in vaccine-induced immunity and protection. (This study has been registered at ClinicalTrials.gov under registration no. NCT00223080.).

A case of episcleral tattooing--an emerging body modification trend.

BACKGROUND: In 2007 an article was published describing the first forays into the practice of episcleral tattooing. Currently only a handful of people worldwide have undergone this procedure, whereby a needle is used to inject dye under the bulbar conjunctiva. To date there have been no previous reports of the risks and complications of this emerging practice in the medical literature. We present a case involving a complication that arose in one of the few people in Britain to have undergone episcleral tattooing for cosmetic purposes. CASE PRESENTATION: A 43-year-old Caucasian man presented to the eye casualty clinic with red, lumpy conjunctivae bilaterally, having undergone episcleral tattooing 7 weeks previously. On examination there were 3 distinct areas of conjunctival swelling in each eye, representing a total of 6 injection sites. No other gross abnormalities were identified. The clinical picture remained unchanged 6 months on, apart from a degree of fading of the conjunctival dye. He will remain under our care to ensure that any further complications such as granulomatous inflammation are managed and documented. CONCLUSION: Episcleral tattooing is carried out by individuals with no medical training. The short-term complications reported so far include: headaches, severe photophobia, persistent foreign body sensation, and migration of ink staining. More serious short-term risks such as infection, globe penetration, and peri-ocular haemorrhage could occur. For now we can only speculate as to the long-term consequences, but these may include carcinogenic change or granulomatous inflammation. We feel that the potential risks of the procedure should be communicated more widely to those body modification practitioners undertaking it. This practice could result in more serious presentations to acute eye services in the future.

Superior ophthalmic vein thrombosis as an initial manifestation of antiphospholipid syndrome.

PURPOSE: To report an uncommon case of superior ophthalmic vein occlusion secondary to antiphospholipid syndrome. METHOD: Interventional case report. RESULT: A 41 year old man who presented with acute proptosis and ophthalmoplegia who was initially treated for orbital cellulitis. His CT scan showed changes consistent of that a superior ophthalmic vein thrombosis. He was managed with high dose intravenous steroid and commenced on anticoagulant therapy. He was subsequently diagnosed with antiphospholipid syndrome. CONCLUSION: Although superior ophthalmic vein occlusion is rare it is an important differential. This is the first reported case secondary to antiphospholipid syndrome.

Demographic effects of road mortality on mammalian populations: a systematic review.

In light of rapidly expanding road networks worldwide, there is increasing global awareness of the growing amount of mammalian roadkill. However, the ways in which road mortality affects the population dynamics of different species remains largely unclear. We aimed to categorise the demographic parameters in mammalian populations around the world that are directly or indirectly affected by road mortality, as well as identify the most effective study designs for quantifying population-level consequences of road mortality. We conducted a comprehensive systematic review to synthesise literature published between 2000 and 2021 and out of 11,238 unique studies returned, 83 studies were retained comprising 69 mammalian species and 150 populations. A bias towards research-intensive countries and larger mammals was apparent. Although searches were conducted in five languages, all studies meeting the inclusion criteria were in English. Relatively few studies (13.3%) provided relevant demographic context to roadkill figures, hampering understanding of the impacts on population persistence. We categorised five direct demographic parameters affected by road mortality: sex- and age-biased mortality, the percentage of a population killed on roads per year (values up to 50% were reported), the contribution of roadkill to total mortality rates (up to 80%), and roadkill during inter-patch or long-distance movements. Female-biased mortality may be more prevalent than previously recognised and is likely to be critical to population dynamics. Roadkill was the greatest source of mortality for 28% of studied populations and both additive and compensatory mechanisms to roadkill were found to occur, bringing varied challenges to conservation around roads. In addition, intra-specific population differences in demographic effects of road mortality were common. This highlights that the relative importance of road mortality is likely to be context specific as the road configuration and habitat quality surrounding a population can vary. Road ecology studies that collect data on key life parameters, such as age/stage/sex-specific survival and dispersal success, and that use a combination of methods are critical in understanding long-term impacts. Quantifying the demographic impacts of road mortality is an important yet complex consideration for proactive road management.

Heat induces multiomic and phenotypic stress propagation in zebrafish embryos.

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecular signatures of this process, by integrating multiomic and phenotypic data. In individual zebrafish embryos, repeated heat peaks elicited both a molecular response and a burst of accelerated growth followed by a growth slowdown in concert with reduced responses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolites including sulfur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signaling, glycosaminoglycan/keratan sulfate, and lipid metabolism. Consequently, non-heat-exposed receivers (exposed to stress metabolites only) experienced accelerated catch-up growth in concert with reduced swimming performance. The combination of heat and stress metabolites accelerated development the most, mediated by apelin signaling. Our results prove the concept of indirect heat-induced stress propagation toward naive receivers, inducing phenotypes comparable with those resulting from direct heat exposure, but utilizing distinct molecular pathways. Group-exposing a nonlaboratory zebrafish line, we independently confirm that the glycosaminoglycan biosynthesis-related gene chs1 and the mucus glycoprotein gene prg4a, functionally connected to the candidate stress metabolite classes sugars and phosphocholine, are differentially expressed in receivers. This hints at the production of Schreckstoff-like cues in receivers, leading to further stress propagation within groups, which may have ecological and animal welfare implications for aquatic populations in a changing climate.

Racial differences in time to blood pressure control of aneurysmal subarachnoid hemorrhage patients: A single-institution study.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 patients annually in the United States. Uncontrolled blood pressure is a major risk factor for aneurysmal subarachnoid hemorrhage. Clinical guidelines recommend maintaining blood pressure control until definitive aneurysm securement occurs. It is unknown whether racial differences exist regarding blood pressure control and outcomes (HLOS, discharge disposition) in aneurysmal subarachnoid hemorrhage. Here, we aim to assess whether racial differences exist in 1) presentation, 2) clinical course, and 3) outcomes, including time to blood pressure stabilization, for aSAH patients at a large tertiary care medical center. METHODS: We conducted a retrospective review of adult aneurysmal subarachnoid hemorrhage cases from 2013 to 2019 at a single large tertiary medical center. Data extracted from the medical record included sex, age, race, insurance status, aneurysm location, aneurysm treatment, initial systolic and diastolic blood pressure, Hunt Hess grade, modified Fisher score, time to blood pressure control (defined as time in minutes from first blood pressure measurement to the first of three consecutive systolic blood pressure measurements under 140mmHg), hospital length of stay, and final discharge disposition. RESULTS: 194 patients met inclusion criteria; 140 (72%) White and 54 (28%) Black. While White patients were more likely than Black patients to be privately insured (62.1% versus 33.3%, p < 0.001), Black patients were more likely than White patients to have Medicaid (55.6% versus 15.0%, p < 0.001). Compared to White patients, Black patients presented with a higher median systolic (165 mmHg versus 148 mmHg, p = 0.004) and diastolic (93 mmHg versus 84 mmHg, p = 0.02) blood pressure. Black patients had a longer median time to blood pressure control than White patients (200 minutes versus 90 minutes, p = 0.001). Black patients had a shorter median hospital length of stay than White patients (15 days versus 18 days, p < 0.031). There was a small but statistically significant difference in modified Fisher score between black and white patients (3.48 versus 3.17, p = 0.04).There were no significant racial differences present in sex, Hunt Hess grade, discharge disposition, complications, or need for further interventions. CONCLUSION: Black race was associated with higher blood pressure at presentation, longer time to blood pressure control, but shorter hospital length of stay. No racial differences were present in aneurysmal subarachnoid hemorrhage associated complications or interventions.

Digital Bodies: A controlled evaluation of a brief classroom-based intervention for reducing negative body image among adolescents in the digital age.

BACKGROUND: A growing body of research has linked social media use to negative body image. AIMS: The present research aimed to evaluate the efficacy of Digital Bodies, a brief classroom-based intervention that aims to improve adolescents' body image. METHODS: British adolescents (N = 290; Age M = 12.81; SD = 0.40; Range = 12-13; Female = 151) were cluster randomized to intervention or waiting list control groups. Measures of body satisfaction, appearance ideal internalization (thin and athletic ideal internalization) and self-objectification were completed at baseline (T1), 1-week post-intervention (T2) and 8-week follow-up (T3). RESULTS: Multi-level modelling showed adolescents in the intervention group reported improved body satisfaction at T2, in comparison to the control, and crucially this effect was sustained at T3. Additionally, girls reported less thin ideal internalization at T2 relative to the control, but this effect was not sustained at T3. No other intervention effects were found. CONCLUSIONS: Overall, the findings provide initial support for the efficacy of Digital Bodies as an intervention for improving adolescents' body satisfaction.

Sino-orbital foreign body caused by a slingshot injury in a young boy.

Slingshots or hand catapults, historically used as a military or hunting weapon, are common toys among children and young teenagers. Their use can be dangerous as a strike to the eye or orbit can result in significant injuries including blindness. We describe a rare case of a sino-orbital foreign body caused by a slingshot injury in a young boy. The case was managed by a multidisciplinary team involving ear, nose and throat, ophthalmology and paediatrics, and the foreign body of a metal ball bearing was removed using an endoscopic transnasal approach. Although the patient made a good recovery, the case highlights the danger of slingshot devices misused by children.

Body talk in the digital age: A controlled evaluation of a classroom-based intervention to reduce appearance commentary and improve body image.

This research evaluates the efficacy of a classroom-based intervention - Body Talk in the Digital Age (BTIDA) - in reducing adolescents' appearance commentary and improving body image. British adolescents (N = 314; Age Range = 12-14) were cluster randomised to intervention or waiting-list control groups. Measures of appearance commentary, appearance ideal internalisation, self-objectification and body satisfaction were completed at baseline (T1), then one-week (T2) and eight-week (T3) post-intervention. Multi-level modelling showed girls who received BTIDA reported less appearance commentary engagement and thin ideal internalisation at T2 and T3, than the control, supporting the partial efficacy of BTIDA for girls. No intervention effects were found among boys.

A global horizon scan of the future impacts of robotics and autonomous systems on urban ecosystems.

Technology is transforming societies worldwide. A major innovation is the emergence of robotics and autonomous systems (RAS), which have the potential to revolutionize cities for both people and nature. Nonetheless, the opportunities and challenges associated with RAS for urban ecosystems have yet to be considered systematically. Here, we report the findings of an online horizon scan involving 170 expert participants from 35 countries. We conclude that RAS are likely to transform land use, transport systems and human-nature interactions. The prioritized opportunities were primarily centred on the deployment of RAS for the monitoring and management of biodiversity and ecosystems. Fewer challenges were prioritized. Those that were emphasized concerns surrounding waste from unrecovered RAS, and the quality and interpretation of RAS-collected data. Although the future impacts of RAS for urban ecosystems are difficult to predict, examining potentially important developments early is essential if we are to avoid detrimental consequences but fully realize the benefits.

Use of magnetically purified Plasmodium falciparum parasites improves the accuracy of erythrocyte invasion assays.

Merozoite invasion of erythrocytes is a crucial step for the asexual cycle of Plasmodium falciparum. Multiple invasion pathways, which involve different ligand-receptor interactions, have been identified in P. falciparum by examining the entry of purified parasite into erythrocytes with different surface receptors, either mutant or under different enzyme treatments. The most critical step for a successful invasion assay is the isolation of erythrocytes infected with viable schizonts. Here, we applied a magnetic column to purify the schizonts for the erythrocyte invasion assay. Comparing to Percoll-sorbitol purification method, this modified approach showed great improvement on reproducibility and reliability of invasion assay, particularly for short-term, culture-adapted parasite isolates. The magnetic purification method is an excellent alternative for parasite isolates that do not tolerate or with unknown sensitivity to Percoll-sorbitol exposure.

Impacts and Potential Mitigation of Road Mortality for Hedgehogs in Europe.

Transport infrastructure is a pervasive element in modern landscapes and continues to expand to meet the demands of a growing human population and its associated resource consumption. Road-induced mortality is often thought to be a major contributor to the marked declines of European hedgehog populations. This review synthesizes available evidence on the population-level impacts of road mortality and the threat to population viability for the five hedgehog species in Europe. Local and national studies suggest that road mortality can cause significant depletions in population sizes, predominantly removing adult males. Traffic collisions are a probable cause of fragmentation effects, subsequently undermining ecological processes such as dispersal, as well as the genetic variance and fitness of isolated populations. Further studies are necessary to improve population estimates and explicitly examine the consequences of sex- and age-specific mortality rates. Hedgehogs have been reported to use crossing structures, such as road tunnels, yet evaluations of mitigation measures for population survival probability are largely absent. This highlights the need for robust studies that consider population dynamics and genetics in response to mitigation. In light of ongoing declines of hedgehog populations, it is paramount that applied research is prioritised and integrated into a holistic spatial planning process.

David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments.

Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications. The development of smaller, antigen binding antibody fragments, derived from conventional antibodies or produced recombinantly, has been growing at a fast pace. Antibody fragments can be used on their own or linked to other molecules to generate numerous possibilities for bispecific, multi-specific, multimeric, or multifunctional molecules, and to achieve a variety of biological effects. They offer several advantages over full-length monoclonal antibodies, particularly a lower cost of goods, and because of their small size they can penetrate tissues, access challenging epitopes, and have potentially reduced immunogenicity. In this review, we will discuss the structure, production, and mechanism of action of EMA/FDA-approved fragments and of those in clinical and pre-clinical development. We will also discuss current topics of interest surrounding the potential use of antibody fragments for intracellular targeting and blood-brain barrier (BBB) penetration.

Rectal adenocarcinoma: rare metastasis to the optic nerve.

We present the first reported case of histologically proven colorectal adenocarcinoma with metastatic spread to the optic nerve. A 49-year-old man, with a known history of rectal adenocarcinoma, presented with progressive loss of vision in his left eye. On presentation, he had no perception to light in his left eye and Snellen acuity of 6/36 in the right eye. Fundus examination showed a left globally swollen optic nerve with a few flame-shaped haemorrhages. A gadolinium-enhanced MRI scan demonstrated abnormal thickening of the anterior and mid-section of the optic nerve with high signal on STIR and postgadolinium enhancement. Optic nerve biopsy confirmed the presence of epithelial adenocarcinoma compatible with metastasis of gut origin. The patient died within 4 months of presentation.