Optical Marker-Based Motion Capture of the Human Spine: A Scoping Review of Study Design and Outcomes.

Biomechanical analysis of the human spine is crucial to understanding injury patterns. Motion capture technology has gained attention due to its non-invasive nature. Nevertheless, traditional motion capture studies consider the spine a single rigid segment, although its alignment changes during movement. Moreover, guidelines that indicate where markers should be placed for a specific exercise do not exist. This study aims to review the methods used to assess spine biomechanics using motion capture systems to determine the marker sets used, the protocols used, the resulting parameters, the analysed activities, and the characteristics of the studied populations. PRISMA guidelines were used to perform a Scoping Review using SCOPUS and Web of Science databases. Fifty-six journal and conference articles from 1997 to 2023 were considered for the analysis. This review showed that Plug-in-Gait is the most used marker set. The lumbar spine is the segment that generates the most interest because of its high mobility and function as a weight supporter. Furthermore, angular position and velocity are the most common outcomes when studying the spine. Walking, standing, and range of movement were the most studied activities compared to sports and work-related activities. Male and female participants were recruited similarly across all included articles. This review presents the motion capture techniques and measurement outcomes of biomechanical studies of the human spine, to help standardize the field. This work also discusses trends in marker sets, study outcomes, studied segments and segmentation approaches.

Clinical and molecular characterization of limb-girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients.

Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.

Development of a whole-cell biosensor for ethylene oxide and ethylene.

Ethylene and ethylene oxide are widely used in the chemical industry, and ethylene is also important for its role in fruit ripening. Better sensing systems would assist risk management of these chemicals. Here, we characterise the ethylene regulatory system in Mycobacterium strain NBB4 and use these genetic parts to create a biosensor. The regulatory genes etnR1 and etnR2 and cognate promoter Petn were combined with a fluorescent reporter gene (fuGFP) in a Mycobacterium shuttle vector to create plasmid pUS301-EtnR12P. Cultures of M. smegmatis mc2-155(pUS301-EtnR12P) gave a fluorescent signal in response to ethylene oxide with a detection limit of 0.2 µM (9 ppb). By combining the epoxide biosensor cells with another culture expressing the ethylene monooxygenase, the system was converted into an ethylene biosensor. The co-culture was capable of detecting ethylene emission from banana fruit. These are the first examples of whole-cell biosensors for epoxides or aliphatic alkenes. This work also resolves long-standing questions concerning the regulation of ethylene catabolism in bacteria.

MOG Antibody-Associated Disease in the Setting of Metastatic Melanoma Complicated by Immune Checkpoint Inhibitor Use.

OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma. METHODS: This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. RESULTS: A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response. DISCUSSION: This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.

Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines.

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers. The working group additionally invited genetic and clinical experts from the USA, India, Japan, Australia, South-Africa, and Brazil to provide a global perspective. Six virtual meetings were organized to reach consensus on the minimal requirements for genetic confirmation of FSHD1 and FSHD2. Here, we present the clinical and genetic features of FSHD, specific features of FSHD1 and FSHD2, pros and cons of established and new technologies (Southern blot in combination with either linear or pulsed-field gel electrophoresis, molecular combing, optical genome mapping, FSHD2 methylation analysis and FSHD2 genotyping), the possibilities and challenges of prenatal testing, including pre-implantation genetic testing, and the minimal requirements and recommendations for genetic confirmation of FSHD1 and FSHD2. This consensus is expected to contribute to current clinical management and trial-readiness for FSHD.

Acute urinary retention in children: causes and the role of bladder catheterization and ultrasonogram.

BACKGROUND: Acute urinary retention in children is uncommon and can be related to several causes. The role of abdominal ultrasound and catheterization is controversial. We aimed to identify the most common causes of acute urinary retention in children, focusing, particularly on the role of bladder catheterization and the diagnostic value of acute ultrasound. METHODS: We retrospectively analyzed all consecutive children admitted to our emergency department with acute urinary retention from 2010 to 2020. Post-operative acute urinary retention, neonatal age, and known urological or neurological disorders were excluded. Diagnostic workup and management were adopted in each patient. Results were compared in patients with more and less than 5 years old. RESULTS: 193 patients were included. Median age was 3 (2-16) years; 53.4% were girls. Ultrasound evaluation was performed in (129/193; 66.8%) patients, more commonly <5-year-old (74% vs. 26%, P<0.01). A previously unknown urological condition was detected in (16/129; 12%). The majority of patients (124/193; 64%) were managed without bladder catheterization. These patients were significantly younger than the remainder (3- vs. 4-year-old, P<0.01) and the most common diagnosis was external genitalia inflammation (53%). Of the remaining patients, (34/69; 49%) restored spontaneous micturition after a single catheterization, whereas 35 required admission. The latter were more commonly males (32%, P=0.01), with higher incidence of abnormal ultrasound (33% vs. 7%, P<0.001). CONCLUSIONS: Acute urinary retention in commonly due to external genitalia inflammation, particularly in patients <5-year-old, and can be generally managed, without bladder catheterization. Abdominal ultrasound is an important diagnostic tool, that should be performed only in selected cases.

Using Motivation Assessment as a Teaching Tool for Large Undergraduate Courses: Reflections From the Teaching Team.

Introduction: Student motivation is a critical predictor of academic achievement, engagement, and success in higher education. Motivating students is a crucial aspect of effective teaching. Statement of the Problem: Although there is a wealth of research on student motivation, practical guidance for putting theory into practice in challenging teaching environments (i.e., large-format introductory courses) is lacking. We discuss a first step toward motivating students: understanding how motivated they are and using that information to inform teaching. Literature Review: Anxiety, impeded motivation, and high student-to-teacher ratio are all challenges associated with teaching foundational introductory courses, such as statistics. The Expectancy-Value-Cost model of motivation provides theoretical background to assist with these courses. We discuss the implementation and use of motivation assessments as a teaching tool. Teaching Implications: Motivation assessments are feasible and useful while teaching large-format introductory courses. Instructor reflections lend insights as to how to use these assessments to improve pedagogy.

Giving a voice to our silent teachers: Whole body donation from the donor perspective at one donation program in the United States.

Human body donors play a crucial role in anatomical education, research, and clinical skills training, and those interested in anatomical donation may bequeath their bodies to body donation programs (BDPs). The purpose of this study was to evaluate the perspective of body donors on the donation process in order to make recommendations for improvement that align with donor values. A survey was administered via email to 2145 individuals that had enrolled in The Ohio State University's BDP and yielded a 40% response rate. Results showed that a majority of registered donors do not place high importance on detailed consent options during the enrollment process, but do value BDP oversight, such as through the use of an oversight committee to supervise the program. Only 9.1% of donors felt that their loved ones should be permitted to make changes to their consent forms after they have passed. Although 96.2% of participants would allow photos/videos to be taken of their donated bodies, females were significantly less likely to consent to this than males (p = 0.001), as well as less likely to allow their donations to be utilized for anatomy outreach (p = 0.023). Racial minorities were significantly less trusting of the university to treat their donation with dignity and respect compared to White registrants (p = 0.034). Suggestions for improving BDP protocols include the implementation of an annual newsletter for registrants, improving methods to spread awareness about donation, increasing transparency during the consent process, and creating resources for donors' families.

An OpenSim-Based Closed-Loop Biomechanical Wrist Model for Subject-Specific Pathological Tremor Simulation.

OBJECTIVE: A pathological tremor (PT) is an involuntary rhythmic movement of varying frequency and amplitude that affects voluntary motion, thus compromising individuals' independence. A comprehensive model incorporating PT's physiological and biomechanical aspects can enhance our understanding of the disorder and provide valuable insights for therapeutic approaches. This study aims to build a biomechanical model of pathological tremors using OpenSim's realistic musculoskeletal representation of the human wrist with two degrees of freedom. METHODS: We implemented a Matlab/OpenSim interface for a forward dynamics simulation, which allows for the modeling, simulation, and design of a physiological H∞ closed-loop control. This system replicates pathological tremors similar to those observed in patients when their arm is extended forward, the wrist is pronated, and the hand is subject to gravity forces. The model was individually tuned to five subjects (four Parkinson's disease patients and one diagnosed with essential tremor), each exhibiting distinct tremor characteristics measured by an inertial sensor and surface EMG electrodes. Simulation agreement with the experiments for EMGs, central frequency, joint angles, and angular velocities were evaluated by Jensen-Shannon divergence, histogram centroid error, and histogram intersection. RESULTS: The model emulated individual tremor statistical characteristics, including muscle activations, frequency, variability, and wrist kinematics, with greater accuracy for the four Parkinson's patients than the essential tremor. CONCLUSION: The proposed model replicated the main statistical features of subject-specific wrist tremor kinematics. SIGNIFICANCE: Our methodology may facilitate the design of patient-specific rehabilitation devices for tremor suppression, such as neural prostheses and electromechanical orthoses.

Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation.

OBJECTIVE: Concerns have been raised about the effect of skin color on the accuracy of transcutaneous bilirubin (TcB) measurements, a widely used method for hyperbilirubinemia diagnosis in newborns. Literature is inconclusive, with both reported under- and overestimations of the TcB with increasing skin pigmentation. Therefore, the influence of skin color on TcB measurements was systematically evaluated in a controlled, in vitro setting. METHODS: A bilirubin meter (JM-105) was evaluated on layered phantoms that mimic neonatal skin with varying dermal bilirubin concentrations (0-250 µmol/L) and varying epidermal melanosome volume fractions (0-40%; light-dark skin color). RESULTS: TcB measurements were influenced by skin pigmentation. Larger mimicked melanosome volume fractions and higher bilirubin levels led to larger underestimations of the measured TcB, compared to an unpigmented epidermis. In the in vitro setting of this study, these underestimations amounted to 26-132 µmol/L at a TcB level of 250 µmol/L. CONCLUSION: This in vitro study provides insight into the effect of skin color on TcB measurements: the TcB is underestimated as skin pigmentation increases and this effect becomes more pronounced at higher bilirubin levels. Our results highlight the need for improved TcB meter design and cautious interpretation of TcB readings on newborns with dark skin. IMPACT: Key message: Skin color influences transcutaneous bilirubin measurements: the darker the skin, the larger the underestimation. What this study adds to existing literature: Existing literature is inconclusive regarding the influence of skin color on transcutaneous bilirubin measurements. This study systematically evaluates and clarifies the influence of skin color on transcutaneous bilirubin measurements in a controlled, in vitro setting. IMPACT: This study aids to better interpret the measured TcB level in patients with varying skin colors, and is particularly important when using TcB meters on patients with dark skin colors.

New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

Investigating the status of whole-body donation across the United States of America.

Dissection of human body donors is a valuable part of anatomical education, research, and clinical training. In the United States, deceased human bodies are predominantly sourced through whole-body donation programs (BDPs) housed by academic institutions. Due to the lack of information regarding BDPs, the aim of this study was to gather information from US BDPs through a survey to better understand the donation process and standard operating procedures of these programs. In 2021, a Qualtrics survey was distributed to 125 BDPs and yielded responses from 72 program leaders. Collectively, these programs received more than 26,000 whole-body donations annually. Findings show that 70% typically receive enough donations to fit the needs of their institutions, 17% receive a surplus of donations, and 13% receive too few donations. Sixty-eight percent of programs permit next of kin body donation regularly or in times of need, and 44% allow next of kin to make changes to a donor's donation form after death. On average, over 85% of the registered donor population is composed of white individuals, and only 6 institutions have methods in place to promote diversity among their donor population. Overall, there is considerable variability in the operation of BDPs across the United States. These findings can be used to make recommendations about donor enrollment and program operations to ultimately improve the donation process. Future research needs to investigate the opinions and preferences of body donors along with their next of kin on the body donation process and associated policies.

The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung.

The mitochondrial adaptor protein p66Shc has been suggested to control life span in mice via the release of hydrogen peroxide. However, the role of p66Shc in lung aging remains unsolved. Thus, we investigated the effects of p66Shc-/- on the aging of the lung and pulmonary circulation. In vivo lung and cardiac characteristics were investigated in p66Shc-/- and wild type (WT) mice at 3, 12, and 24 months of age by lung function measurements, micro-computed tomography (µCT), and echocardiography. Alveolar number and muscularization of small pulmonary arteries were measured by stereology and vascular morphometry, respectively. Protein and mRNA levels of senescent markers were measured by western blot and PCR, respectively. Lung function declined similarly in WT and p66Shc-/- mice during aging. However, µCT analyses and stereology showed slightly enhanced signs of aging-related parameters in p66Shc-/- mice, such as a decline of alveolar density. Accordingly, p66Shc-/- mice showed higher protein expression of the senescence marker p21 in lung homogenate compared to WT mice of the corresponding age. Pulmonary vascular remodeling was increased during aging, but aged p66Shc-/- mice showed similar muscularization of pulmonary vessels and hemodynamics like WT mice. In the heart, p66Shc-/- prevented the deterioration of right ventricular (RV) function but promoted the decline of left ventricular (LV) function during aging. p66Shc-/- affects the aging process of the lung and the heart differently. While p66Shc-/- slightly accelerates lung aging and deteriorates LV function in aged mice, it seems to exert protective effects on RV function during aging.

Pediatric Optic Pathway Gliomas Resource Utilization and Prevalence in the OptumLabs Data Warehouse.

BACKGROUND: Although significant progress has been made in improving the rate of survival for pediatric optic pathway gliomas (OPGs), data describing the methods of diagnosis and treatment for OPGs are limited in the modern era. This retrospective study aims to provide an epidemiological overview in the pediatric population and an update on eye care resource utilization in OPG patients using big data analysis. METHODS: Using the OptumLabs Data Warehouse, 9-11 million children from 2016 to 2021 assessed the presence of an OPG claim. This data set was analyzed for demographic distribution data and clinical data including average ages for computed tomography (CT), MRI, strabismus, and related treatment (surgery, chemotherapy, and radiation), as well as yearly rates for optical coherence tomography (OCT) and visual field (VF) examinations. RESULTS: Five hundred fifty-one unique patients ranging in age from 0 to 17 years had an OPG claim, with an estimated prevalence of 4.6-6.1 per 100k. Among the 476 OPG patients with at least 6 months of follow-up, 88.9% had at least one MRI and 15.3% had at least one CT. Annual rates for OCT and VF testing were similar (1.26 vs 1.35 per year), although OCT was ordered for younger patients (mean age = 9.2 vs 11.7 years, respectively). During the study period, 14.1% of OPG patients had chemotherapy, 6.1% had either surgery or radiation, and 81.7% had no treatment. CONCLUSIONS: This study updates OPG demographics for the modern era and characterizes the burden of the treatment course for pediatric OPG patients using big data analysis of a commercial claims database. OPGs had a prevalence of about 0.005% occurring equally in boys and girls. Most did not receive treatment, and the average child had at least one claim for OCT or VF per year for clinical monitoring. This study is limited to only commercially insured children, who represent approximately half of the general child population.

Graduate anatomy education: How are we training the future generations of anatomy educators?

The teaching of anatomy is relevant to many fields and anatomy teachers are in demand. Individuals with a graduate anatomy education are some of the most sought-after candidates to fill open teaching positions, but it is unclear as to what constitutes a graduate anatomy education. The purpose of this study was to investigate the components of a graduate anatomy education in the United States. A survey regarding the components of doctoral, master's, and graduate certificate programs was distributed to program directors and department chairs at 71 US institutions. Respondents indicated that there were 17 doctoral, 28 master's, and 9 graduate certificate programs. Students completed coursework in all the traditional anatomical subdisciplines in approximately half of doctoral (53%) and master's (57%) programs, though the number was lower in graduate certificate programs (22%). In comparison, within 12 programs (5 doctoral, 4 master's, and 3 graduate certificate) students were required to complete coursework in less than 2 anatomical subdisciplines. Required coursework outside the subdisciplines usually involved educational theories and practices (61% of programs), research methods (52% of programs), and/or physiology (37% of programs). Respondents indicated that most programs (81%) were designed to prepare their students to teach. It appears that graduate anatomy training likely involves gross anatomy coursework, coursework in another anatomical subdiscipline, and coursework in educational theories and practices. Given the likely decline in the number of doctoral-level anatomy programs from 21 to 19, serious consideration should be given to hiring teaching candidates with master's or graduate certificate training in anatomy.

How long have we been mistaken? Multi-tools shedding light into the systematics of the widespread deep-water genus Madrepora Linnaeus, 1758 (Scleractinia).

Deep-water coral reefs are found worldwide and harbor biodiversity levels that are comparable to their shallow-water counterparts. However, the genetic diversity and population structure of deep-water species remain poorly explored, and historical taxonomical issues still need to be resolved. Here we used microsatellite markers as well as ultraconserved elements (UCE) and exons to shed light on the population structure, genetic diversity, and phylogenetic position of the genus Madrepora, which contains M. oculata, one of the most widespread scleractinian species. Population structure of 107 samples from three Southwestern Atlantic sedimentary basins revealed the occurrence of a cryptic species, herein named M. piresae sp. nov. (authored by Kitahara, Capel and Zilberberg), which can be found in sympatry with M. oculata. Phylogeny reconstructions based on 134 UCEs and exon regions corroborated the population genetic data, with the recovery of two well-supported groups, and reinforced the polyphyly of the family Oculinidae. In order to better accommodate the genus Madrepora, while reducing taxonomical confusion associated with the name Madreporidae, we propose the monogeneric family Bathyporidae fam. nov. (authored by Kitahara, Capel, Zilberberg and Cairns). Our findings advance the knowledge on the widespread deep-water genus Madrepora, resolve a long-standing question regarding the phylogenetic position of the genus, and highlight the need of a worldwide review of the genus.

Toward a Cenozoic history of atmospheric CO2.

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO2) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO2 record spanning the past 66 million years. This newly constructed record provides clearer evidence for higher Earth system sensitivity in the past and for the role of CO2 thresholds in biological and cryosphere evolution.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

New frontiers in intraoperative neurophysiologic monitoring: a narrative review.

Background and Objective: Neurological insults during surgery arise from anatomic and/or physiologic perturbations. Intraoperative neurophysiologic monitoring (IONM) fills a critical role of ensuring that any neurological insults during certain surgical procedures are caught in real-time to prevent patient harm. IONM provides immediate feedback to the surgeon and anesthesiologist about the need for an intervention to prevent a neurologic deficit postoperatively. As important as it seems to have IONM available to any patient having surgery where a neurological injury is possible, the truth is that IONM is unavailable to large swaths of people around the world. This review is intended to bring attention to all of the ways IONM is critically important for a variety of surgeries and highlight the barriers preventing most patients around the world from benefiting from the technology. Expansion of IONM to benefit patients from all over the world is the new frontier. Methods: We searched all English language original papers and reviews using Embase and MEDLINE/PubMed databases published from 1995 to 2022. Different combinations of the following search terms were used: intraoperative neuromonitoring, neurosurgery, low-income countries, cost, safety, and efficacy. Key Content and Findings: We describe common IONM modalities used during surgery as well as explore barriers to implementation of IONM in resource-limited regions. Additionally, we describe ongoing efforts to establish IONM capabilities in new locations around the world. Conclusions: In this paper, we performed a review of the literature on IONM with an emphasis on the basic understanding of clinical applications and the barriers for expansion into resource-limited settings. Finally, we provide our interpretation of "new frontiers" in IONM quite literally facilitating access to the tools and education so a hospital in Sub-Saharan Africa can incorporate IONM for their high-risk surgeries.