Distinct checkpoint and homolog biorientation pathways regulate meiosis I in Drosophila oocytes.

Mitosis and meiosis have two mechanisms for regulating the accuracy of chromosome segregation: error correction and the spindle assembly checkpoint (SAC). We have investigated the function of several checkpoint proteins in meiosis I of Drosophila oocytes. Evidence of a SAC response by several of these proteins is found upon depolymerization of microtubules by colchicine. However, unattached kinetochores or errors in biorientation of homologous chromosomes does not induce a SAC response. Furthermore, the metaphase I arrest does not depend on SAC genes, suggesting the APC is inhibited even if the SAC is silenced. Two SAC proteins, ROD of the ROD-ZW10-Zwilch (RZZ) complex and MPS1, are also required for the biorientation of homologous chromosomes during meiosis I, suggesting an error correction function. Both proteins aid in preventing or correcting erroneous attachments and depend on SPC105R for localization to the kinetochore. We have defined a region of SPC105R, amino acids 123-473, that is required for ROD localization and biorientation of homologous chromosomes at meiosis I. Surprisingly, ROD removal, or "streaming", is independent of the dynein adaptor Spindly and is not linked to the stabilization of end-on attachments. Instead, meiotic RZZ streaming appears to depend on cell cycle stage and may be regulated independently of kinetochore attachment or biorientation status. We also show that dynein adaptor Spindly is also required for biorientation at meiosis I, and surprisingly, the direction of RZZ streaming.

Transitional Palliative Care for Family Caregivers: Outcomes From a Randomized Controlled Trial.

CONTEXT: Patients receiving inpatient palliative care often face physical and psychological uncertainties during transitions out of the hospital. Family caregivers often take on responsibilities to ensure patient safety, quality of care, and extend palliative care principles, but often without support or training, potentially compromising their health and well-being. OBJECTIVES: This study tested an eight-week intervention using video visits between palliative care nurse interventionists and caregivers to assess changes in caregiver outcomes and patient quality of life. METHODS: This randomized controlled trial, conducted from 2018 to 2022, enrolled adult caregivers in rural or medically underserved areas in Minnesota, Wisconsin, and Iowa. Eligible caregivers included those caring for patients who received inpatient palliative care and transitioned out of the hospital. The intervention group received teaching, guidance, and counseling from a palliative care nurse before and for eight weeks after hospital discharge. The control group received monthly phone calls but no intervention. Caregiver outcomes included changes in depression, burden, and quality of life, and patient quality of life, as reported by the caregiver. RESULTS: Of those consented, 183 completed the intervention, and 184 completed the control arm; 158 participants had complete baseline and eight-week data. In unadjusted analyses, the intervention group and their care recipients showed statistically significant improvements in quality of life compared to the control group. Improvements persisted in adjusted analyses, and depression significantly improved. No differences in caregiver burden were observed. CONCLUSION: Addressing rural caregivers' needs during transitions in care can enhance caregiver outcomes and improve patient quality of life.

Failure to treat ventricular tachycardia or ventricular fibrillation by implantable cardioverter-defibrillators.

BACKGROUND: Normally functioning implantable cardioverter-defibrillators (ICDs) with intact lead systems occasionally fail to deliver therapy for ventricular tachycardia/fibrillation (VT/VF) or deliver it only after clinically significant delays (failure-to-treat). OBJECTIVE: We aimed to investigate ICD failure-to-treat VT/VF in a large patient cohort. METHODS: We searched the US Food and Drug Administration's online Manufacturer and User Facility Device Experience (MAUDE) database from 2019 to 2023 for manufacturer-verified reports in which normally functioning ICDs failed to treat VT/VF. RESULTS: We identified 854 reports classified as deaths (n = 96 [11.2%]), injuries (n = 585 [68.5%]), or malfunctions (n = 173 [20.3%]) for normally functioning ICDs. The most common causes were misclassification as supraventricular tachycardia (SVT) or atrial fibrillation (AF; 54.8%), undersensing (21.1%), and failure to satisfy programmed rate/duration criteria (8.7%). Most events caused by misclassification as SVT/AF (89.5%) and failure to satisfy rate/duration criteria (70.3%) were VT; most caused by undersensing were either VF (54.4%) or not specified as VT or VF (19.4%). Undersensing caused 65.6% of deaths, although it represented only 21.1% of reports. In the United States, the number of reports increased faster than that of ICD patients. CONCLUSION: In the largest reported series of failure-to-treat VT/VF by normally functioning ICDs, the most common cause was misclassification of VT as SVT/AF; the most common cause of death was undersensing of VF. Although relatively few patients with normally functioning ICDs experience failure-to-treat VT/VF, the absolute number of verified MAUDE reports suggests that more work is needed to quantify the magnitude of the problem, to identify root causes, and to develop solutions.

Saphenous Vein Graft Pseudoaneurysm Treated With Covered Stenting.

Saphenous vein graft (SVG) pseudoaneurysms are an infrequent, but life-threatening complication of coronary artery bypass grafting (CABG) surgery if left untreated. Here, we discuss the case of a 77-year-old patient, with a prior history of CABG and transcatheter aortic valve implantation (TAVI), who was incidentally found on computed tomography angiography (CTA) to have a pseudoaneurysm of his SVG with an initial chief complaint of dizziness. Despite increasing reports of SVG pseudoaneurysm, there is no consensus on definitive treatment. Due to the high mortality risk of this patient with surgical intervention, a minimally invasive percutaneous coronary intervention was performed. The patient was effectively treated with two overlapping Viabahn-covered stents, which completely excluded the pseudoaneurysm. Follow-up imaging at two months showed two well-positioned overlapping self-expanding stents with total occlusion of the pseudoaneurysm.

Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity.

BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.

mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction.

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that is active in nearly all proliferating eukaryotic cells; however, it is unclear whether mTORC1 activity changes throughout the cell cycle. We find that mTORC1 activity oscillates from lowest in mitosis/G1 to highest in S/G2. The interphase oscillation is mediated through the TSC complex but is independent of major known regulatory inputs, including Akt and Mek/Erk signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex. mTORC1 has long been known to promote progression through G1. We find that mTORC1 also promotes progression through S and G2 and is important for satisfying the Chk1/Wee1-dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together, these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific consequences for proliferating cells.

The Next Generation: Surgeon Learning Curve in a Mature Operative Rib Management Program.

INTRODUCTION: Prior work has demonstrated utility in using operative time to measure surgeon learning for surgical stabilization of rib fractures (SSRF); however, no studies have used operative time to evaluate the benefit of proctoring in subsequent generations of surgeons. We sought to evaluate whether there is a difference in learning between an original series (TOS) of self-taught surgeons versus the next generation (TNG) of proctored surgeons using cumulative summation (CUSUM) analysis. We hypothesized that TNG would have a comparatively accelerated learning curve. METHODS: A single-center retrospective review of all SSRF at a level 1 trauma center was performed. Data were collected from the beginning of an operative chest injury program to include at least 2 y of TNG experience. Operative time was used to determine success and misstep based on prior methods. Learning curves using CUSUM analysis were calculated based on an anticipated success rate of 90% and compared between TOS and TNG groups. RESULTS: Over 7 y, 163 patients with a median Injury Severity Score of 24 underwent SSRF. Median operative time was 165 min with a 0.5 plate-to-fracture ratio. All three TOS surgeons experienced a positive slope indicative of early missteps for their first 15-20 cases. By contrast, all three TNG surgeons demonstrated a series of early successes resulting in negative CUSUM slopes which coincided with a period of proctoring. By the end of TNG series, the composite cumulative score was less than half of the TOS surgeon' scores. CONCLUSIONS: Operative time continues to be a useful surrogate for observing SSRF learning curves. In a mature institutional program, proctored novice surgeons appear to have an accelerated learning curve compared to novice surgeons developing a new operative rib program.

Trends in heart failure costs for commercially insured patients in the United States (2006-2021).

BACKGROUND: Although prior research has estimated the overarching cost burden of heart failure (HF), a thorough analysis examining medical expense differences and trends, specifically among commercially insured patients with heart failure, is still lacking. Thus, the study aims to examine historical trends and differences in medical costs for commercially insured heart failure patients in the United States from 2006 to 2021. METHODS: A population-based, cross-sectional analysis of medical and pharmacy claims data (IQVIA PharMetrics® Plus for Academic) from 2006 to 2021 was conducted. The cohort included adult patients (age > = 18) who were enrolled in commercial insurance plans and had healthcare encounters with a primary diagnosis of HF. The primary outcome measures were the average total annual payment per patient and per cost categories encompassing hospitalization, surgery, emergency department (ED) visits, outpatient care, post-discharge care, and medications. The sub-group measures included systolic, diastolic, and systolic combined with diastolic, age, gender, comorbidity, regions, states, insurance payment, and self-payment. RESULTS: The study included 422,289 commercially insured heart failure (HF) patients in the U.S. evaluated from 2006 to 2021. The average total annual cost per patient decreased overall from $9,636.99 to $8,201.89, with an average annual percentage change (AAPC) of -1.11% (95% CI: -2% to -0.26%). Hospitalization and medication costs decreased with an AAPC of -1.99% (95% CI: -3.25% to -0.8%) and - 3.1% (95% CI: -6.86-0.69%). On the other hand, post-discharge, outpatient, ED visit, and surgery costs increased by an AAPC of 0.84% (95% CI: 0.12-1.49%), 4.31% (95% CI: 1.03-7.63%), 7.21% (95% CI: 6.44-8.12%), and 9.36% (95% CI: 8.61-10.19%). CONCLUSIONS: The study's findings reveal a rising trend in average total annual payments per patient from 2006 to 2015, followed by a subsequent decrease from 2016 to 2021. This decrease was attributed to the decline in average patient costs within the Medicare Cost insurance category after 2016, coinciding with the implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015. Additionally, expenses related to surgical procedures, emergency department (ED) visits, and outpatient care have shown substantial growth over time. Moreover, significant differences across various variables have been identified.

Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation in Drosophila oocytes.

The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein SPC105R/KNL1 in driving meiosis I chromosome segregation through lateral attachments to microtubules and coorientation of sister centromeres. To identify the domains of SPC105R that are critical for meiotic chromosome segregation, an RNAi-resistant gene expression system was developed. We found that the SPC105R C-terminal domain (aa 1284-1960) is necessary and sufficient for recruiting NDC80 to the kinetochore and building the outer kinetochore. Furthermore, the C-terminal domain recruits BUBR1, which in turn recruits the cohesion protection proteins MEI-S332 and PP2A. Of the remaining 1283 amino acids, we found the first 473 are most important for meiosis. The first 123 amino acids of the N-terminal half of SPC105R contain the conserved SLRK and RISF motifs that are targets of PP1 and Aurora B kinase and are most important for regulating the stability of microtubule attachments and maintaining metaphase I arrest. The region between amino acids 124 and 473 are required for lateral microtubule attachments and biorientation of homologues, which are critical for accurate chromosome segregation in meiosis I.

Physiochemical and Electrochemical Properties of a Heat-Treated Electrode for All-Iron Redox Flow Batteries.

Iron redox flow batteries (IRFBs) are cost-efficient RFBs that have the potential to develop low-cost grid energy storage. Electrode kinetics are pivotal in defining the cycle life and energy efficiency of the battery. In this study, graphite felt (GF) is heat-treated at 400, 500 and 600 °C, and its physicochemical and electrochemical properties are studied using XPS, FESEM, Raman and cyclic voltammetry. Surface morphology and structural changes suggest that GF heat-treated at 500 °C for 6 h exhibits acceptable thermal stability while accessing the benefits of heat treatment. Specific capacitance was calculated for assessing the wettability and electrochemical properties of pristine and treated electrodes. The 600 °C GF has the highest specific capacitance of 34.8 Fg-1 at 100 mV s-1, but the 500 °C GF showed the best battery performance. The good battery performance of the 500 °C GF is attributed to the presence of oxygen functionalities and the absence of thermal degradation during heat treatment. The battery consisting of 500 °C GF electrodes offered the highest voltage efficiency of ~74%, Coulombic efficiency of ~94%, and energy efficiency of ~70% at 20 mA cm-2. Energy efficiency increased by 7% in a battery consisting of heat-treated GF in comparison to pristine GF. The battery is capable of operating for 100 charge-discharge cycles with an average energy efficiency of ~ 67% for over 100 cycles.

Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation in Drosophila oocytes.

The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein SPC105R/KNL1 in driving meiosis I chromosome segregation through lateral attachments to microtubules and co-orientation of sister centromeres. To identify the domains of SPC105R that are critical for meiotic chromosome segregation, an RNAi-resistant gene expression system was developed. We found that SPC105R's C-terminal domain (aa 1284-1960) is necessary and sufficient for recruiting NDC80 to the kinetochore and building the outer kinetochore. Furthermore, the C-terminal domain recruits BUBR1, which in turn recruits the cohesion protection proteins MEI-S332 and PP2A. Of the remaining 1283 amino acids, we found the first 473 are most important for meiosis. The first 123 amino acids of the N-terminal half of SPC105R contain the conserved SLRK and RISF motifs that are targets of PP1 and Aurora B kinase and are most important for regulating the stability of microtubule attachments and maintaining metaphase I arrest. The region between amino acids 124 and 473 are required for two activities that are critical for accurate chromosome segregation in meiosis I, lateral microtubule attachments and bi-orientation of homologs.

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 trial of MEC chemotherapy combined with uproleselan for relapsed/refractory AML showed a median overall survival of 8.8 months and low (2%) rates of severe oral mucositis. Clinical trials seek to confirm activity in AML and mitigation of neutrophil-mediated adverse events (mucositis and diarrhea) after intensive chemotherapy. In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials.

Leveraging big data for causal understanding in mental health: a research framework.

Over the past 30 years there have been numerous large-scale and longitudinal psychiatric research efforts to improve our understanding and treatment of mental health conditions. However, despite the huge effort by the research community and considerable funding, we still lack a causal understanding of most mental health disorders. Consequently, the majority of psychiatric diagnosis and treatment still operates at the level of symptomatic experience, rather than measuring or addressing root causes. This results in a trial-and-error approach that is a poor fit to underlying causality with poor clinical outcomes. Here we discuss how a research framework that originates from exploration of causal factors, rather than symptom groupings, applied to large scale multi-dimensional data can help address some of the current challenges facing mental health research and, in turn, clinical outcomes. Firstly, we describe some of the challenges and complexities underpinning the search for causal drivers of mental health conditions, focusing on current approaches to the assessment and diagnosis of psychiatric disorders, the many-to-many mappings between symptoms and causes, the search for biomarkers of heterogeneous symptom groups, and the multiple, dynamically interacting variables that influence our psychology. Secondly, we put forward a causal-orientated framework in the context of two large-scale datasets arising from the Adolescent Brain Cognitive Development (ABCD) study, the largest long-term study of brain development and child health in the United States, and the Global Mind Project which is the largest database in the world of mental health profiles along with life context information from 1.4 million people across the globe. Finally, we describe how analytical and machine learning approaches such as clustering and causal inference can be used on datasets such as these to help elucidate a more causal understanding of mental health conditions to enable diagnostic approaches and preventative solutions that tackle mental health challenges at their root cause.

Approaching toxigenic Clostridia from a One Health perspective.

Spore-forming pathogens have a unique capacity to thrive in diverse environments, and with temporal persistence afforded through their ability to sporulate. Their prevalence in diverse ecosystems requires a One Health approach to identify critical reservoirs and outbreak-associated transmission chains, given their capacity to freely move across soils, waterways, foodstuffs and as commensals or infecting pathogens in human and animal populations. Among anaerobic spore-formers, genomic resources for pathogens including C. botulinum, C. difficile, and C. perfringens enable our capacity to identify common and unique factors that support their persistence in diverse reservoirs and capacity to cause disease. Publicly available genomic resources for spore-forming pathogens at NCBI's Pathogen Detection program aid outbreak investigations and longitudinal monitoring in national and international programs in public health and food safety, as well as for local healthcare systems. These tools also enable research to derive new knowledge regarding disease pathogenesis, and to inform strategies in disease prevention and treatment. As global community resources, the continued sharing of strain genomic data and phenotypes further enhances international resources and means to develop impactful applications. We present examples showing use of these resources in surveillance, including capacity to assess linkages among clinical, environmental, and foodborne reservoirs and to further research investigations into factors promoting their persistence and virulence in different settings.

mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction.

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that stimulates anabolic cell growth while suppressing catabolic processes such as autophagy. mTORC1 is active in most, if not all, proliferating eukaryotic cells. However, it remains unclear whether and how mTORC1 activity changes from one cell cycle phase to another. Here we tracked mTORC1 activity through the complete cell cycle and uncover oscillations in its activity. We find that mTORC1 activity peaks in S and G2, and is lowest in mitosis and G1. We further demonstrate that multiple mechanisms are involved in controlling this oscillation. The interphase oscillation is mediated through the TSC complex, an upstream negative regulator of mTORC1, but is independent of major known regulatory inputs to the TSC complex, including Akt, Mek/Erk, and CDK4/6 signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex, and instead involves CDK1-dependent control of the subcellular localization of mTORC1 itself. Functionally, we find that in addition to its well-established role in promoting progression through G1, mTORC1 also promotes progression through S and G2, and is important for satisfying the Wee1- and Chk1- dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific functional consequences in proliferating cells.

Approaching pathogenic Clostridia from a One Health perspective.

Spore-forming pathogens have a unique capacity to thrive in diverse environments, and with temporal persistence afforded through their ability to sporulate. These behaviors require a One Health approach to identify critical reservoirs and outbreak-associated transmission chains, given their capacity to freely move across soils, waterways, foodstuffs, and as commensals or infecting pathogens in human and veterinary populations. Among anaerobic spore-formers, genomic resources for pathogens including C. botulinum, C. difficile, and C. perfringens enable our capacity to identify common and unique factors that support their persistence in diverse reservoirs and capacity to cause disease. Publicly available genomic resources for spore-forming pathogens at NCBI's Pathogen Detection program aid outbreak investigations and longitudinal monitoring in national and international programs in public health and food safety, as well as for local healthcare systems. These tools also enable research to derive new knowledge regarding disease pathogenesis, and to inform strategies in disease prevention and treatment. As global community resources, the continued sharing of strain genomic data and phenotypes further enhances international resources and means to develop impactful applications. We present examples showing use of these resources in surveillance, including capacity to assess linkages among clinical, environmental, and foodborne reservoirs and to further research investigations into factors promoting their persistence and virulence in different settings.

The use of a fluorine mass balance to demonstrate the mineralization of PFAS by high frequency and high power ultrasound.

High-frequency ultrasound (sonolysis) has been shown as a practical approach for mineralizing PFAS in highly concentrated PFAS waste. However, a fluorine mass balance approach showing complete mineralization for ultrasound treatment has not been elucidated. The impact of ultrasonic power density (W/L) and the presence of co-occurring PFAS on the degradation of individual PFAS are not well understood. In this research, the performance of a 10L sonochemical reactor was assessed for treating synthetic high-concentration PFAS waste with carboxylic and sulfonic perfluoroalkyl surfactants ranging in chain length from four to eight carbons at three different initial concentrations: 6, 55, 183 µM. The mass balance for fluorine was performed using three analytical techniques: triple quadrupole liquid chromatography-mass spectrometry, a fluoride ion selective electrode, and 19F nuclear magnetic resonance. The test results showed near complete mineralization of PFAS in the waste without the formation of intermediate fluorinated by-products. The PFAS mineralization efficiency of the sonolysis treatment at two different power densities for similar initial concentrations were almost identical; the G value at 145 W/L was 9.7*10-3 g/kWh, whereas the G value at 90 W/L was 9.3*10-3 g/kWh. The results of this study highlight the implications for the scalability of the sonolytic process to treat high-concentration PFAS waste.

Steroidogenic Factor-1 form and function: From phospholipids to physiology.

Steroidogenic Factor-1 (SF-1, NR5A1) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors, consisting of a DNA-binding domain (DBD) connected to a transcriptional regulatory ligand binding domain (LBD) via an unstructured hinge domain. SF-1 is a master regulator of development and adult function along the hypothalamic pituitary adrenal and gonadal axes, with strong pathophysiological association with endometriosis and adrenocortical carcinoma. SF-1 was shown to bind and be regulated by phospholipids, one of the most interesting aspects of SF-1 regulation is the manner in which SF-1 interacts with phospholipids: SF-1 buries the phospholipid acyl chains deep in the hydrophobic core of the SF-1 protein, while the lipid headgroups remain solvent-exposed on the exterior of the SF-1 protein surface. Here, we have reviewed several aspects of SF-1 structure, function and physiology, touching on other transcription factors that help regulate SF-1 target genes, non-canonical functions of SF-1, the DNA-binding properties of SF-1, the use of mass spectrometry to identify lipids that associate with SF-1, how protein phosphorylation regulates SF-1 and the structural biology of the phospholipid-ligand binding domain. Together this review summarizes the form and function of Steroidogenic Factor-1 in physiology and in human disease, with particular emphasis on adrenal cancer.

A Comparative Evaluation of Conventional Instrumentation and Accelerometer-Based Navigation in the Practice of a High-Volume Unicompartmental Knee Arthroplasty (UKA) Surgeon.

Background: Component malpositioning and joint malalignment following unicompartmental knee arthroplasty (UKA) increase the risk for revision. This study investigates whether accelerometer-based navigation (NAV) decreases radiographic outliers with respect to component placement and joint alignment in comparison to conventional instrumentation in UKA. Methods: A radiographic review of UKAs was performed by a single surgeon following adoption of an accelerometry-guided navigation system (OrthAlign, Aliso Viejo, CA). This cohort was then compared to previous patients undergoing UKA with conventional instrumentation. Six-week postoperative radiographs were used to compare femoral coronal and sagittal angles, tibial coronal and sagittal angles, the net coronal angle, tibial component rotation, and medial tibial overhang. Outliers in implant positioning were compared between groups. Patient variables including age, gender, body mass index, American Society of Anesthesiology, and surgical time (incision until the start of closure) were also compared between groups. Results: Eighty-eight UKA's were reviewed (49 conventional instrumentation [CI] patients; 39 NAV patients). Using 2-sample t-tests, no significant differences were found in patient demographics, radiographic parameters, and operative times between the CI and NAV cohorts. Using chi-squared tests, no significant difference was found in the number of radiographic outliers between the CI and NAV cohorts. Conclusions: Our study found that a high-volume UKA surgeon achieved a low rate of radiographic outliers in both NAV and CI cohorts. This data suggests that NAV is no different from conventional instrumentation with respect to implant positioning, overall joint alignment, and operative time when used by a high-volume UKA surgeon.