The Five-Factor Modified Frailty Index as a Predictor of Outcomes in Deep Brain Stimulation Surgery for Parkinson's Disease.

Introduction Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Though there are many pharmacological therapeutics approved today for PD, surgical interventions such as deep brain stimulation (DBS) have shown convincing symptom mitigation and minimal complication rates in aggregate. Recently, the concept of frailty - defined as reduced physiologic reserve and function affecting multiple systems throughout the patient - has gained traction as a predictor of short-term postoperative morbidity and mortality. As such, the Modified Frailty Index-5 (mFI-5) is a postoperative morbidity predictor based on five factors and has been used in neurosurgical subspecialties such as tumor, vascular, and spine. Yet, there is minimal literature assessing frailty in the field of functional neurosurgery. With the prevalence of DBS in PD, this study evaluated the mFI-5 as a predictor of postoperative complications in a selected patient population. Methods The American College of Surgeons National Surgical Quality Improvement Program 2010-2019 Database was queried for Current Procedural Terminology (CPT) codes, as well as the International Classification of Diseases (ICD)-9 and ICD-10 codes pertaining to DBS procedures in PD patients. Each patient was scored by the mFI-5 protocol and stratified into groups of No Frailty (mFI-5=0), Moderate Frailty (mFI-5=1), and Significant Frailty (mFI-5≥2). The No Frailty group was used as a reference in multivariate and univariate analyses of the groups. Results A total of 1,645 subjects were included in the study and were subcategorized into groups of No Frailty (N=877), Moderate Frailty (N=561), and Significant Frailty (N=207) based on their frailty scores. The subjects' mean age was 65.8±9.4 years. Overall, 1,161 (70.6%) were male, while 484 (29.4%) were female. With reference to the No Frailty group in multivariate analysis, patients with moderate frailty experienced greater unplanned readmission (OR 2.613, 95% CI 1.143-5.973, p=0.023), while those with significant frailty experienced greater unplanned readmission (OR 3.723, 95% CI 1.376-10.073, p=0.010), any readmission (OR 2.396, 95% CI 1.098-5.230, p=0.028), non-home discharge (OR 4.317, 95% CI 1.765-10.562, p<0.001), and complications in aggregate (OR 2.211, 95% CI 1.285-3.806, p=0.004). Conclusions Until now, the available clinical tools were limited in providing accurate predictions with minimal information for postoperative outcomes in DBS for PD patients. Our data give clinicians insight into the relationship between frailty and surgical outcomes and will assist physicians in preparing for postoperative care by predicting outcomes of significantly frail PD patients receiving DBS therapy.

Enhancing survivorship and growth of juvenile Montipora capitata using the Hawaiian collector urchin Tripneustes gratilla.

The biodiversity of coral reef habitats is rapidly declining due to the effects of anthropogenic climate change, prompting the use of active restoration as a mitigation strategy. Sexual propagation can maintain or enhance genetic diversity in restoration of these ecosystems, but these approaches suffer from a range of inefficiencies in rearing and husbandry. Algal overgrowth of juveniles is a major bottleneck in the production of sexually propagated corals that may be alleviated by co-culture with herbivores. We reared juvenile Montipora capitata alongside juvenile native Hawaiian collector urchins, Tripneustes gratilla, for 15 weeks and documented significant ecological benefits of co-culture. Urchin treatments significantly increased the survivorship of coral aggregates (14%) and individual settlers (24%). We also documented a significant increase in coral growth in the presence of urchins. These results demonstrate the utility of microherbivory in promoting coral growth and survivorship in ex situ conditions, providing valuable insight for restoration pipelines of native Hawaiian coral species.

The Anterior Versus Posterior Approach for Interbody Fusion in Patients Who Are Classified as Obese: A Retrospective Cohort Study of 9,021 Patients From a National Database.

Introduction Lumbar spine interbody fusions have been performed to relieve back pain and improve stability due to various underlying pathologies. Anterior interbody fusion and posterior interbody fusion approaches are two main approaches that are classically compared. In an attempt to compare these two approaches to the spine, large retrospective national database reviews have been performed to compare and predict 30-day postoperative outcomes; however, they have conflicting findings. Obesity, defined as having a body mass index (BMI) over 30 kg/m2, may also contribute to the extent of spine pathology and is associated with increased rates of postoperative complications. Complication rates in patients who are obese have yet to be thoroughly investigated using a large national database. Our present investigation aims to make this comparison using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. The goal of the present study is to utilize a nationwide prospective database to determine short-term differences in postoperative outcomes between posterior and anterior lumbar fusion in patients with obesity and relate these findings to previous studies in the general population. Methods A retrospective cohort analysis was conducted on 9,021 patient data from the ACS-NSQIP database from 2015 to 2019 who underwent an elective, single-level fusion via anterior or posterior surgical approach. This database captures over 150 clinical variables on individual patient cases, including demographic data, preoperative risk factors and laboratory values, intraoperative data, and significant events up to postoperative day 30. All outcome measures were included in this analysis with special attention to rates of deep venous thrombosis (DVT) and pulmonary embolism (PE), prolonged length of stay (LOS), reoperation, and operation time. Results Multivariable analysis controlling for age, BMI, sex, race, functional status, American Society of Anesthesiologists (ASA) class, and selected comorbidities with P < 0.05 demonstrated that the anterior approach was an independent predictor for all significant outcomes except prolonged length of stay. Compared to the posterior approach, the anterior approach had a shorter total operation time (B = -13.257, 95% confidence interval (CI) [-17.522, -8.992], P < 0.001), higher odds of deep vein thrombosis (odds ratio (OR) = 2.210, 95% CI [1.211, 4.033], P= 0.010), and higher odds of pulmonary embolism (OR = 2.679, 95% CI [1.311, 5.477], P = 0.007) and was protective against unplanned reoperation (OR = 0.702, 95% CI [0.548, 0.898], P = 0.005). Conclusions The obese population makes up a large and growing demographic of those undergoing spine surgery, and as such, it is pertinent to investigate the differences, advantages, and disadvantages of lumbar fusion approaches in this group. While anterior approaches may be protective of longer operation time and unplanned reoperation, this benefit may not be clinically significant when considering an increased risk of DVT and PE. Given the short-term nature of this dataset and the limitations inherent in large de-identified retrospective database studies, these findings are interpreted with caution. Longer-term follow-up studies accounting for confounding variables with spine-centered outcomes will be necessary to further elucidate these nuances.

Genetic patterns in Montipora capitata across an environmental mosaic in Kane'ohe Bay, O'ahu, Hawai'i.

Spatial genetic structure (SGS) is important to a population's ability to adapt to environmental change. For species that reproduce both sexually and asexually, the relative contribution of each reproductive mode has important ecological and evolutionary implications because asexual reproduction can have a strong effect on SGS. Reef-building corals reproduce sexually, but many species also propagate asexually under certain conditions. To understand SGS and the relative importance of reproductive mode across environmental gradients, we evaluated genetic relatedness in almost 600 colonies of Montipora capitata across 30 environmentally characterized sites in Kane'ohe Bay, O'ahu, Hawaii, using low-depth restriction digest-associated sequencing. Clonal colonies were relatively rare overall but influenced SGS. Clones were located significantly closer to one another spatially than average colonies and were more frequent on sites where wave energy was relatively high, suggesting a strong role of mechanical breakage in their formation. Excluding clones, we found no evidence of isolation by distance within sites or across the bay. Several environmental characteristics were significant predictors of the underlying genetic variation (including degree heating weeks, time spent above 30°C, depth, sedimentation rate and wave height); however, they only explained 5% of this genetic variation. Our results show that asexual fragmentation contributes to the ecology of branching corals at local scales and that genetic diversity is maintained despite strong environmental gradients in a highly impacted ecosystem, suggesting potential for broad adaptation or acclimatization in this population.

Intrapopulation adaptive variance supports thermal tolerance in a reef-building coral.

Coral holobionts are multi-species assemblages, which adds significant complexity to genotype-phenotype connections underlying ecologically important traits like coral bleaching. Small scale heterogeneity in bleaching is ubiquitous in the absence of strong environmental gradients, which provides adaptive variance needed for the long-term persistence of coral reefs. We used RAD-seq, qPCR and LC-MS/MS metabolomics to characterize host genomic variation, symbiont community and biochemical correlates in two bleaching phenotypes of the vertically transmitting coral Montipora capitata. Phenotype was driven by symbiosis state and host genetic variance. We documented 5 gene ontologies that were significantly associated with both the binary bleaching phenotype and symbiont composition, representing functions that confer a phenotype via host-symbiont interactions. We bred these corals and show that symbiont communities were broadly conserved in bulk-crosses, resulting in significantly higher survivorship under temperature stress in juveniles, but not larvae, from tolerant parents. Using a select and re-sequence approach, we document numerous gene ontologies selected by heat stress, some of which (cell signaling, antioxidant activity, pH regulation) have unique selection dynamics in larvae from thermally tolerant parents. These data show that vertically transmitting corals may have an adaptive advantage under climate change if host and symbiont variance interact to influence bleaching phenotype.

Coral bleaching response is unaltered following acclimatization to reefs with distinct environmental conditions.

Urgent action is needed to prevent the demise of coral reefs as the climate crisis leads to an increasingly warmer and more acidic ocean. Propagating climate change-resistant corals to restore degraded reefs is one promising strategy; however, empirical evidence is needed to determine whether stress resistance is affected by transplantation beyond a coral's native reef. Here, we assessed the performance of bleaching-resistant individuals of two coral species following reciprocal transplantation between reefs with distinct pH, salinity, dissolved oxygen, sedimentation, and flow dynamics to determine whether heat stress response is altered following coral exposure to novel physicochemical conditions in situ. Critically, transplantation had no influence on coral heat stress responses, indicating that this trait was relatively fixed. In contrast, growth was highly plastic, and native performance was not predictive of performance in the novel environment. Coral metabolic rates and overall fitness were higher at the reef with higher flow, salinity, sedimentation, and diel fluctuations of pH and dissolved oxygen, and did not differ between native and cross-transplanted corals, indicating acclimatization via plasticity within just 3 mo. Conversely, cross-transplants at the second reef had higher fitness than native corals, thus increasing the fitness potential of the recipient population. This experiment was conducted during a nonbleaching year, so the potential benefits to recipient population fitness are likely enhanced during bleaching years. In summary, this study demonstrates that outplanting bleaching-resistant corals is a promising tool for elevating the resistance of coral populations to ocean warming.

A Field Primer for Monitoring Benthic Ecosystems using Structure-from-Motion Photogrammetry.

Structure-from-motion (SfM) photogrammetry is a technique used to generate three-dimensional (3D) reconstructions from a sequence of two-dimensional (2D) images. SfM methods are becoming increasingly popular as a noninvasive way to monitor many systems, including anthropogenic and natural landscapes, geologic structures, and both terrestrial and aquatic ecosystems. Here, a detailed protocol is provided for collecting SfM imagery to generate 3D models of benthic habitats. Additionally, the cost, time efficiency, and output quality of employing a Digital Single Lens Reflex (DSLR) camera versus a less expensive action camera have been compared. A tradeoff between computational time and resolution was observed, with the DSLR camera producing models with more than twice the resolution, but taking approximately 1.4-times longer to produce than the action camera. This primer aims to provide a thorough description of the steps necessary to collect SfM data in benthic habitats for those who are unfamiliar with the technique as well as for those already using similar methods.

Emerging therapies in Friedreich's Ataxia.

INTRODUCTION: Friedreich's ataxia (FRDA) is a progressive, neurodegenerative disease that results in gait and limb ataxia, diabetes, cardiac hypertrophy, and scoliosis. At the cellular level, FRDA results in the deficiency of frataxin, a mitochondrial protein that plays a vital role in iron homeostasis and amelioration of oxidative stress. No cure currently exists for FRDA, but exciting therapeutic developments which target different parts of the pathological cascade are on the horizon. AREAS COVERED: Areas covered include past and emerging therapies for FRDA, including antioxidants and mitochondrial-related agents, nuclear factor erythroid-derived 2-related factor 2 (Nrf2) activators, deuterated polyunsaturated fatty acids, iron chelators, histone deacetylase (HDAC) inhibitors, trans-activator of transcription (TAT)-frataxin, interferon gamma (IFNγ), erythropoietin, resveratrol, gene therapy, and anti-sense oligonucleotides (ASOs), among others. EXPERT OPINION: While drug discovery has been challenging, new and exciting prospective treatments for FRDA are currently on the horizon, including pharmaceutical agents and gene therapy. Agents that enhance mitochondrial function, such as Nrf2 activators, dPUFAs and catalytic antioxidants, as well as novel methods of frataxin augmentation and genetic modulation will hopefully provide treatment for this devastating disease.

Impact of ocean acidification on the hypoxia tolerance of the woolly sculpin, Clinocottus analis.

As we move into the Anthropocene, organisms inhabiting marine environments will continue to face growing challenges associated with changes in ocean pH (ocean acidification), dissolved oxygen (dead zones) and temperature. These factors, in combination with naturally variable environments such as the rocky intertidal zone, may create extreme physiological challenges for organisms that are already performing near their biological limits. Although numerous studies have examined the impacts of climate-related stressors on intertidal animals, little is known about the underlying physiological mechanisms driving adaptation to ocean acidification and how this may alter organism interactions, particularly in marine vertebrates. Therefore, we have investigated the effects of decreased ocean pH on the hypoxia response of an intertidal sculpin, Clinocottus analis. We used both whole-animal and biochemistry-based analyses to examine how the energetic demands associated with acclimation to low-pH environments may impact the fish's reliance on facultative air breathing in low-oxygen environments. Our study demonstrated that acclimation to ocean acidification resulted in elevated routine metabolic rates and acid-base regulatory capacity (Na+,K+-ATPase activity). These, in turn, had downstream effects that resulted in decreased hypoxia tolerance (i.e. elevated critical oxygen tension). Furthermore, we present evidence that these fish may be living near their physiological capacity when challenged by ocean acidification. This serves as a reminder that the susceptibility of teleost fish to changes in ocean pH may be underestimated, particularly when considering the multiple stressors that many experience in their natural environments.

Embryonic overexpression of receptors for advanced glycation end-products by alveolar epithelium induces an imbalance between proliferation and apoptosis.

Receptors for advanced glycation end-products (RAGEs) are multiligand cell surface receptors highly expressed in the lung that contribute to alveolar epithelial cell differentiation during embryogenesis and the modulation of pulmonary inflammation during disease. When RAGEs are overexpressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. However, the possible mechanisms that lead to the disappearance of pulmonary tissue remain unclear. A time course of lung organogenesis, commencing on Embryonic Day (E) 12.5, demonstrated that increased RAGE expression primarily alters lung morphogenesis beginning on E16.5. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunohistochemistry and immunoblotting for active caspase-3 confirmed a shift toward apoptosis in lungs from RAGE-overexpressing mice, compared with wild-type control mice. This observation supports previous work where electron microscopy identified the cellular blebbing of alveolar epithelium in embryonic RAGE-overexpressing mice. Assaying for NF-κB also revealed elevated nuclear translocation in lungs from transgenic mice compared with control mice. An RT-PCR assessment of genes regulated by NF-κB demonstrated the elevated expression of Fas ligand, suggesting increased activity of the Fas-mediated signal transduction pathway in which ligand-receptor interactions trigger cell death. These data provide evidence that the expression of RAGEs must be tightly regulated during homeostatic organogenesis. Further elucidations of the RAGE signaling potentially involved in cell-cycle abnormalities may provide insights into the progression of RAGE-mediated lung diseases.