Halofilins as emerging bactofilin families of archaeal cell shape plasticity orchestrators.

Bactofilins are rigid, nonpolar bacterial cytoskeletal filaments that link cellular processes to specific curvatures of the cytoplasmic membrane. Although homologs of bactofilins have been identified in archaea and eukaryotes, functional studies have remained confined to bacterial systems. Here, we characterize representatives of two families of archaeal bactofilins from the pleomorphic archaeon Haloferax volcanii, halofilin A (HalA) and halofilin B (HalB). HalA and HalB polymerize in vitro, assembling into straight bundles. HalA polymers are highly dynamic and accumulate at positive membrane curvatures in vivo, whereas HalB forms more static foci that localize in areas of local negative curvatures on the outer cell surface. Gene deletions and live-cell imaging show that halofilins are critical in maintaining morphological integrity during shape transition from disk (sessile) to rod (motile). Morphological defects in ΔhalA result in accumulation of highly positive curvatures in rods but not in disks. Conversely, disk-shaped cells are exclusively affected by halB deletion, resulting in flatter cells. Furthermore, while ΔhalA and ΔhalB cells imprecisely determine the future division plane, defects arise predominantly during the disk-to-rod shape remodeling. The deletion of halA in the haloarchaeon Halobacterium salinarum, whose cells are consistently rod-shaped, impacted morphogenesis but not cell division. Increased levels of halofilins enforced drastic deformations in cells devoid of the S-layer, suggesting that HalB polymers are more stable at defective S-layer lattice regions. Our results suggest that halofilins might play a significant mechanical scaffolding role in addition to possibly directing envelope synthesis.

Intravenous Drug Use-Associated Infective Endocarditis in Pregnant Patients at a Hospital in West Virginia.

Introduction Due to high levels of intravenous drug use (IVDU) in West Virginia (WV), there are increasing numbers of hospitalizations for infective endocarditis (IE). More specifically, pregnant patients with IE are a uniquely challenging population, with complex management and a clinical course that further affects the health of the fetus, with high morbidity and mortality. Timely recognition and awareness of the most common bacterial causes will provide hospitals and clinicians with valuable information to manage future patients. Methods This retrospective study analyzed the clinical course of pregnant patients admitted with IE and IVDU history presenting at Cabell Huntington Hospital from 2013 to 2018. Inclusion criteria were women between 16 and 45 years of age confirmed to be pregnant by urine pregnancy test and ultrasonography with at least eight weeks gestation, with a first-time diagnosis of endocarditis and an identified history of IVDU. We excluded charts with pre-existing risk factors including a history of valvular disease, rheumatic heart disease, surgical valve repair or mechanical valve replacement, or a diagnosis of coagulopathies. The resulting charts were evaluated for isolated organisms, reported clinical course, and complications of the pregnancy. Results A total of 10 patients were identified, with methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Serratia marcescens, Haemophilus parainfluenza, and Enterococcus faecalis species. Complications included loss of fetus (30%), septic embolization (40%), hemorrhagic stroke (10%), and transfer to outside facilities for cardiothoracic surgical intervention (40%). Discussion IE in pregnancy, while rare, has serious complications. In the context of the IVDU epidemic, it has an increasing impact on WV hospitals. A better understanding of the clinical course may allow for early diagnosis and guide the development of rational empiric therapies. More effective management of IE in pregnant patients can reduce complications and potentially improve maternal and fetal morbidity or mortality.

Protective effect of allopurinol in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

Introduction: Contrast-induced nephropathy (CIN) is the third most common cause of iatrogenic acute renal failure and is triggered by administration of radiopaque contrast media. Periprocedural hydration is imperative in prevention of CIN, and uric acid has been recognized to have an integral role in development of renal disease. The aim of our study is to understand the efficacy of allopurinol in preventing CIN among patients undergoing percutaneous coronary intervention. Material and methods: A literature search was performed on PubMed (Medline), Science Direct and Cochrane Library using a combination of Mesh terms. We limited our search to randomized controlled trials (RCTs) and articles published in the English language. The PRISMA protocol was utilized to conduct this meta-analysis. Results: Six studies were included in the final analysis. All included studies were clinical trials conducted between 2013 and 2019. A total of 853 patients were included. There was a significant reduction in the risk of CIN among patients who were pretreated with adequate hydration plus allopurinol (100 to 600 mg) compared to hydration only before undergoing percutaneous coronary angiography (RR = 0.39, 95% CI: 0.21-0.73). A sensitivity analysis of studies using 300 mg of allopurinol only reported a significant reduction in CI-AKI compared to hydration alone (RR = 0.26, 95% CI: 0.11-0.57). Conclusions: Our study demonstrates that Allopurinol is effective in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Larger clinical trials are warranted to better understand this effect.

Comparison of Transradial and Transfemoral Approaches for Coronary Angiography and Percutaneous Intervention in Patients with Coronary Bypass Grafts.

OBJECTIVE: We sought to compare the transradial and transfemoral approaches for coronary angiography and percutaneous intervention in patients with coronary artery bypass grafts in terms of volume of radiographic contrast administered during cardiac catheterization, fluoroscopy time, and total procedure time. BACKGROUND: The transradial access has been increasingly used as an alternative to transfemoral. Several studies demonstrated that such access is associated with lower rates of vascular and bleeding complications. Although coronary artery bypass graft patients comprise a significant portion of the coronary artery disease population, this subpopulation was often excluded or underrepresented in transradial access studies. METHODS: Single center, retrospective cohort study. In the study period, all patients who had previously undergone coronary artery bypass graft surgery and had received cardiac catheterization at our institution were included in the study population. RESULTS: A total of 2153 patients were included in the study. From these, 1937 were performed by femoral artery and 216 by transradial approach. Compared to the transfemoral approach, transradial access was associated with lower contrast use (136.3 ±â€¯74.4 ml vs. 122.8 ±â€¯59.1 ml, p = 0.035) and longer fluoroscopy time (13.9 ±â€¯25.6 min vs. 15.9 ±â€¯14.3 min, p < 0.001). CONCLUSION: Diagnostic and interventional catheterization through the transradial approach in patients with previous coronary artery bypass graft surgery was associated with less contrast amount used and longer fluoroscopy time compared to the transfemoral approach. The transradial approach was also associated with lower crossover rates and less vascular complications.

Simulation of Flow in a Complex Aquifer System Subjected to Long-Term Well Network Growth.

In west-central Lower Peninsula of Michigan, population growth and expanded agricultural activities over recent decades have resulted in significant increases in distributed groundwater withdrawals. The growth of the extensive well network and anecdotes of water shortages (dry wells) have raised concerns over the region's groundwater sustainability. We developed an unsteady, three-dimensional (3D) groundwater flow model to describe system dynamics over the last 50 years and evaluate long-term impacts of groundwater use. Simulating this large aquifer system was challenging; the site is characterized by strong, spatially distributed, and statistically nonstationary heterogeneity, making it difficult to avoid over-parameterization using traditional approaches for conceptualizing and calibrating a flow model. Moreover, traditional pumping and water level data were lacking and prohibitively expensive to collect given the large-scale and long-term nature of this study. An integrated, stochastic-deterministic approach was developed to characterize the system and calibrate the flow model through innovative use of high-density water well datasets. This approached allowed (1) implementation of a "zone-based," nonstationary stochastic approach to conceptualize complex spatial variability using a small set of geologic material types; (2) modeling the spatiotemporal evolution of many water well withdrawals across several decades using sector-based parameterization; and (3) critical analysis of long-term water level changes at different locations in the aquifer system for characterizing the system dynamics and calibrating the model. Results show the approach is reasonably successful in calibrating a complex model for a highly complex site in a way that honors complex distributed heterogeneity and stress configurations.

A Case of Leptomeningeal Carcinomatosis from Aggressive Metastatic Prostate Cancer.

Leptomeningeal carcinomatosis (LC) is a rare leptomeningeal spread of diffusely metastatic tumors. It occurs more commonly with hematologic tumors, less commonly with solid tumors, and is exceedingly rare in prostate cancer. Due to its scarcity, it has traditionally been difficult to diagnose LC but advancement of MRI has helped considerably. However, even with technological improvements, pre-mortem diagnosis of LC remains difficult and controversial. Our case is a 71-year-old male with prostate cancer with bone metastases who presented to our facility with altered mental status (AMS), lower extremity weakness, and worsening diarrhea. The diarrhea was responsive to antibiotic therapy, but his AMS did not resolve. A head CT without contrast was negative but follow-up brain MRI revealed leptomeningeal enhancement highly suggestive of LC. Cerebrospinal fluid (CSF) cytology results were negative and other CSF studies were inconclusive. Although further studies were planned, the patient continued to deteriorate, and the family elected to withdraw care. He passed away without beginning treatment for the LC. Despite advances in cancer therapies, LC remains difficult to diagnose and treat. Imaging may be suggestive of the condition but the confirmatory tests such as repeated CSF cytology or meningeal biopsy are not only invasive but also usually occur postmortem. Additional methods of CSF testing have been studied to evaluate their role in accurately diagnosing LC but low specificity for LC has somewhat limited their use. Although treatment options are mainly palliative in nature, prompt recognition and early treatment could grant valuable time for patients and families.

A Multiscale Assessment of Shallow Groundwater Salinization in Michigan.

Managing nonpoint-source (NPS) pollution of groundwater systems is a significant challenge because of the heterogeneous nature of the subsurface, high costs of data collection, and the multitude of scales involved. In this study, we assessed a particularly complex NPS groundwater pollution problem in Michigan, namely, the salinization of shallow aquifer systems due to natural upwelling of deep brines. We applied a system-based approach to characterize, across multiple scales, the integrated groundwater quantity-quality dynamics associated with the brine upwelling process, assimilating a variety of modeling tools and data-including statewide water well datasets scarcely used for larger scientific analysis. Specifically, we combined (1) data-driven modeling of massive amounts of groundwater/geologic information across multiple spatial scales with (2) detailed analysis of groundwater salinity dynamics and process-based flow modeling at local scales. Statewide "hotspots" were delineated and county-level severity rankings were developed based on dissolved chloride (Cl- ) concentration percentiles. Within local hotspots, the relative impact of upwelling was determined to be controlled by: (1) streams-which act as "natural pumps" that bring deeper (more mineralized) groundwater to the surface; (2) the occurrence of nearly impervious geologic material at the surface-which restricts fresh water dilution of deeper, saline groundwater; and (3) the space-time evolution of water well withdrawals-which induces slow migration of saline groundwater from its natural course. This multiscale, data-intensive approach significantly improved our understanding of the brine upwelling processes in Michigan, and has applicability elsewhere given the growing availability of statewide water well databases.

Data-Driven Approach for Analyzing Hydrogeology and Groundwater Quality Across Multiple Scales.

Recent trends of assimilating water well records into statewide databases provide a new opportunity for evaluating spatial dynamics of groundwater quality and quantity. However, these datasets are scarcely rigorously analyzed to address larger scientific problems because they are of lower quality and massive. We develop an approach for utilizing well databases to analyze physical and geochemical aspects of groundwater systems, and apply it to a multiscale investigation of the sources and dynamics of chloride (Cl- ) in the near-surface groundwater of the Lower Peninsula of Michigan. Nearly 500,000 static water levels (SWLs) were critically evaluated, extracted, and analyzed to delineate long-term, average groundwater flow patterns using a nonstationary kriging technique at the basin-scale (i.e., across the entire peninsula). Two regions identified as major basin-scale discharge zones-the Michigan and Saginaw Lowlands-were further analyzed with regional- and local-scale SWL models. Groundwater valleys ("discharge" zones) and mounds ("recharge" zones) were identified for all models, and the proportions of wells with elevated Cl- concentrations in each zone were calculated, visualized, and compared. Concentrations in discharge zones, where groundwater is expected to flow primarily upwards, are consistently and significantly higher than those in recharge zones. A synoptic sampling campaign in the Michigan Lowlands revealed concentrations generally increase with depth, a trend noted in previous studies of the Saginaw Lowlands. These strong, consistent SWL and Cl- distribution patterns across multiple scales suggest that a deep source (i.e., Michigan brines) is the primary cause for the elevated chloride concentrations observed in discharge areas across the peninsula.

Understanding the Groundwater Hydrology of a Geographically-Isolated Prairie Fen: Implications for Conservation.

The sources of water and corresponding delivery mechanisms to groundwater-fed fens are not well understood due to the multi-scale geo-morphologic variability of the glacial landscape in which they occur. This lack of understanding limits the ability to effectively conserve these systems and the ecosystem services they provide, including biodiversity and water provisioning. While fens tend to occur in clusters around regional groundwater mounds, Ives Road Fen in southern Michigan is an example of a geographically-isolated fen. In this paper, we apply a multi-scale groundwater modeling approach to understand the groundwater sources for Ives Road fen. We apply Transition Probability geo-statistics on more than 3000 well logs from a state-wide water well database to characterize the complex geology using conditional simulations. We subsequently implement a 3-dimensional reverse particle tracking to delineate groundwater contribution areas to the fen. The fen receives water from multiple sources: local recharge, regional recharge from an extensive till plain, a regional groundwater mound, and a nearby pond. The regional sources deliver water through a tortuous, 3-dimensional "pipeline" consisting of a confined aquifer lying beneath an extensive clay layer. Water in this pipeline reaches the fen by upwelling through openings in the clay layer. The pipeline connects the geographically-isolated fen to the same regional mound that provides water to other fen clusters in southern Michigan. The major implication of these findings is that fen conservation efforts must be expanded from focusing on individual fens and their immediate surroundings, to studying the much larger and inter-connected hydrologic network that sustains multiple fens.