Implementing risk-based approaches to improve drinking water quality in small water supplies in the Nordic region - barriers and solutions.

Small water supplies face similar problems worldwide, regardless of ownership or management type. Non-compliance with water quality regulations is more frequent in small supplies than in large ones, as are waterborne disease outbreaks. The new European Union Drinking Water Directive requires risk-based approach (RBA) to secure water safety as is recommended in the World Health Organization's Guidelines for drinking water quality through 'water safety plans'. This is already in regulation in the Nordic countries, although less used in small supplies. In this research, we explore the challenges, barriers and possible solutions to implementing RBA and improving compliance in small supplies. This was achieved by conducting and analysing interviews with 53 stakeholders from all eight Nordic countries to produce recommendations for action by the different implicated actors. Our findings suggest the centrality of governmental policy, including support for continuous training, provision of simple RBA guidelines and increasing cooperation in the water sector. The Nordic experience reflects global challenges with small water supplies and the trend towards systematic preventive management epitomized in the framework for drinking water safety advocated by the World Health Organization since 2004.

Peptide-Functionalized Carbon Nanotube Chemiresistors: The Effect of Nanotube Density on Gas Sensing.

Biorecognition element (BRE)-based carbon nanotube (CNT) chemiresistors have tremendous potential to serve as highly sensitive, selective, and power-efficient volatile organic compound (VOC) sensors. While many research groups have studied BRE-functionalized CNTs in material science and device development, little attention has been paid to optimizing CNT density to improve chemiresistor performance. To probe the effect of CNT density on VOC detection, we present the chemiresistor-based sensing results from two peptide-based CNT devices counting more than 60 different individual measurements. We find that a lower CNT density shows a significantly higher noise level and device-to-device variation while exhibiting mildly better sensitivity. Further investigation with SEM images suggests that moderately high CNT density with a stable connection of the nanotube network is desirable to achieve the best signal-to-noise ratio. Our results show an essential design guideline for tuning the nanotube density to provide sensitive and stable chemiresistors.

Gastrointestinal stromal tumor: a review of current and emerging therapies.

Gastrointestinal stromal tumors (GIST) are rare neoplasms arising from the interstitial cell of Cajal in the gastrointestinal tract. Two thirds of GIST in adult patients have c-Kit mutation and smaller fractions have platelet derived growth factor receptor alpha (PDGFRA) mutation. Surgery is the only curative treatment for localized disease. Imatinib improves survival when used adjuvantly and in advanced disease. Several targeted therapies have also improved survival in GIST patients after progression on imatinib including sunitinib and regorafenib. Recently, United States Federal and Drug Administration (FDA) approved two new tyrosine kinase inhibitors for the treatment of heavily pretreated advanced/unresectable GIST including avapritinib (a selective inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib (a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this article, we will provide a comprehensive review of GIST including the current standard of care treatment and exploring future paradigm shifts in therapy.

Microfluidic Thermal Flowmeters for Drug Injection Monitoring.

This paper presents a microfluidic thermal flowmeter for monitoring injection pumps, which is essential to ensure proper patient treatment and reduce medication errors that can lead to severe injury or death. The standard gravimetric method for flow-rate monitoring requires a great deal of preparation and laboratory equipment and is impractical in clinics. Therefore, an alternative to the standard method suitable for remote, small-scale, and frequent infusion-pump monitoring is in great demand. Here, we propose a miniaturized thermal flowmeter consisting of a silicon substrate, a platinum heater layer on a silicon dioxide thin-membrane, and a polymer microchannel to provide accurate flow-rate measurement. The present thermal flowmeter is fabricated by the micromachining and micromolding process and exhibits sensitivity, linearity, and uncertainty of 0.722 mW/(g/h), 98.7%, and (2.36 ± 0.80)%, respectively, in the flow-rate range of 0.5-2.5 g/h when the flowmeter is operated in the constant temperature mode with the channel width of 0.5 mm. The measurement range of flow rate can be easily adjusted by changing the cross-sectional microchannel dimension. The present miniaturized thermal flowmeter shows a high potential for infusion-pump calibration in clinical settings.

A Dual Approach of an Oil-Membrane Composite and Boron-Doped Diamond Electrode to Mitigate Biofluid Interferences.

Electrochemical biosensors promise a simple method to measure analytes for both point-of-care diagnostics and continuous, wearable biomarker monitors. In a liquid environment, detecting the analyte of interest must compete with other solutes that impact the background current, such as redox-active molecules, conductivity changes in the biofluid, water electrolysis, and electrode fouling. Multiple methods exist to overcome a few of these challenges, but not a comprehensive solution. Presented here is a combined boron-doped diamond electrode and oil-membrane protection approach that broadly mitigates the impact of biofluid interferents without a biorecognition element. The oil-membrane blocks the majority of interferents in biofluids that are hydrophilic while permitting passage of important hydrophobic analytes such as hormones and drugs. The boron-doped diamond then suppresses water electrolysis current and maintains peak electrochemical performance due to the foulant-mitigation benefits of the oil-membrane protection. Results show up to a 365-fold reduction in detection limits using the boron-doped diamond electrode material alone compared with traditional gold in the buffer. Combining the boron-doped diamond material with the oil-membrane protection scheme maintained these detection limits while exposed to human serum for 18 h.

Ras and exosome signaling.

Ras gene (HRAS, NRAS, and KRAS) has been observed to be mutated and hyper-activated in a significant proportion of cancers. However, mutant Ras remains a challenging therapeutic target. Similarly, inhibition of targets upstream and downstream of Ras has shown limited clinical utility. There have been attempts to develop and deliver mutant K-Ras silencing RNAs either through their encapsulation in liposomes or nanoparticles. However, these approaches show very limited success due to the lack of stability of such carrier molecules alongside associated toxicity. There is a pressing need for the identification of better therapeutic targets for Ras or its associated pathways as well as improvements in the design of superior RNAi delivery systems to suppress mutant K-Ras. More than a decade ago, it was shown that aggregates of palmitoylated Ras isoforms (H-Ras and N-Ras) passage through the cytosol on rapidly moving nanosized particles ("rasosomes"). Fast forward a decade, considerable new knowledge has emerged in the area of small vesicles, microparticles, and exosomes. Exosomes are tiny vesicles and play a significant role in regulating cancer-related signaling pathways. Exosomes have also been studied as delivery vehicles to transport drugs, proteins, and microRNAs of choice for therapeutic purposes. K-Ras pathway proteins have been implicated in exosome biogenesis and extravasation processes. This review provides an update on the current knowledge related to K-Ras signaling and exosomes and also discusses how these tiny vesicles can be harnessed to successfully deliver the K-Ras silencing moieties.

Achievements and Challenges for Real-Time Sensing of Analytes in Sweat within Wearable Platforms.

Physiological sensors in a wearable form have rapidly emerged on the market due to technological breakthroughs and have become nearly ubiquitous with the Apple Watch, FitBit, and other wearable devices. While these wearables mostly monitor simple biometric signatures, new devices that can report on the human readiness level through sensing molecular biomarkers are critical to optimizing the human factor in both commercial sectors and the Department of Defense. The military is particularly interested in real-time, wearable, minimally invasive monitoring of fatigue and human performance to improve the readiness and performance of the war fighter. However, very few devices have ventured into the realm of reporting directly on biomarkers of interest. Primarily this is because of the difficulties of sampling biological fluids in real-time and providing accurate readouts using highly selective and sensitive sensors. When additional restrictions to only use sweat, an excretory fluid, are enforced to minimize invasiveness, the demands on sensors becomes even greater due to the dilution of the biomarkers of interest, as well as variability in salinity, pH, and other physicochemical variables which directly impact the read-out of real-time biosensors. This Account will provide a synopsis not only on exemplary demonstrations and technological achievements toward implementation of real-time, wearable sweat sensors but also on defining problems that still remain toward implementation in wearable devices that can detect molecular biomarkers for real world applications. First, the authors describe the composition of minimally invasive biofluids and then identify what biomarkers are of interest as biophysical indicators. This Account then reviews demonstrated techniques for extracting biofluids from the site of generation and transport to the sensor developed by the authors. Included in this discussion is a detailed description on biosensing recognition elements and transducers developed by the authors to enable generation of selective electrochemical sensing platforms. The authors also discuss ongoing efforts to identify biorecognition elements and the chemistries necessary to enable high affinity, selective biorecognition elements. Finally, this Account presents the requirements for wearable, real-time sensors to be (1) highly stable, (2) portable, (3) reagentless, (4) continuous, and (5) responsive in real-time, before delving into specific methodologies to sense classes of biomarkers that have been explored by academia, government laboratories, and industry. Each platform has its areas of greatest utility, but also come with corresponding weaknesses: (1) ion selective electrodes are robust and have been demonstrated in wearables but are limited to detection of ions, (2) enzymatic sensors enable indirect detection of metabolites and have been demonstrated in wearables, but the compounds that can be detected are limited to a subset of small molecules and the sensors are sensitive to flow, (3) impedance-based sensors can detect a wide range of compounds but require further research and development for deployment in wearables. In conclusion, while substantial progress has been made toward wearable molecular biosensors, substantial barriers remain and need to be solved to enable deployment of minimally invasive, wearable biomarker monitoring devices that can accurately report on psychophysiological status.

Impact of Self-Assembled Monolayer Design and Electrochemical Factors on Impedance-Based Biosensing.

Real-time sensing of proteins, especially in wearable devices, remains a substantial challenge due to the need to convert a binding event into a measurable signal that is compatible with the chosen analytical instrumentation. Impedance spectroscopy enables real-time detection via either measuring electrostatic interactions or electron transfer reactions while simultaneously being amenable to miniaturization for integration into wearable form-factors. To create a more robust methodology for optimizing impedance-based sensors, additional fundamental studies exploring components influencing the design and implementation of these sensors are needed. This investigation addresses a sub-set of these issues by combining optical and electrochemical characterization to validate impedance-based sensor performance as a function of (1) biorecognition element density, (2) self-assembled monolayer chain length, (3) self-assembled monolayer charge density, (4) the electrochemical sensing mechanism and (5) the redox reporter selection. Using a pre-existing lysozyme aptamer and lysozyme analyte combination, we demonstrate a number of design criteria to advance the state-of-the-art in protein sensing. For this model system we demonstrated the following: First, denser self-assembled monolayers yielded substantially improved sensing results. Second, self-assembled monolayer composition, including both thickness and charge density, changed the observed peak position and peak current. Third, single frequency measurements, while less informative, can be optimized to replace multi-frequency measurements and in some cases (such as that with zwitterionic self-assembled monolayers) are preferred. Finally, various redox reporters traditionally not used in impedance sensing should be further explored. Collectively, these results can help limit bottlenecks associated with device development, enabling realization of next-generation impedance-based biosensing with customize sensor design for the specific application.

Perioperative and oncological outcomes of abdominoperineal resection in the prone position vs the classic lithotomy position: A systematic review with meta-analysis.

BACKGROUND AND OBJECTIVES: This study is a systematic review with meta-analysis designed to compare the perioperative and oncological outcomes of the abdominoperineal resection (APR) carried out in the prone jack-knife position (P-APR) vs the classic lithotomy position (C-APR). METHODS: We conducted an electronic search through PubMed utilizing the PRISMA guidelines. We included all randomized and nonrandomized studies which allowed for comparative analysis between the two groups. Research that focused on and analyzed the extralevator abdominal excision were excluded. Pooled variables and number of events were analyzed using the random-effect model. RESULTS: The final analysis included seven nonrandomized retrospective cohorts encompassing 1663 patients. P-APR was associated with decreased operative time (OT) (DM, -43.8 minutes; P < 0.01) and estimated blood loss (EBL) (DM, 86.9 mL; P < 0.01). There were no observed differences regarding perineal wound infections (PWI) (odds ratio [OR], 0.36; P = 0.18), intraoperative perforation of rectum (IOP) (OR, 0.98; P = 0.97), circumferential resection margin (CRM) positivity (OR, 1.02; P = 0.98) or 5-year LR (OR, 1.00; P = 0.99). CONCLUSION: The prone approach for APR is associated with decreased EBL and OT, although not with any change in the incidence of PWI or IOP. Moreover, surgical positioning per se does not appear to affect the CRM positivity rates or LR rate.

"Pigmented Extramammary Paget Disease"-A Potential Mimicker of Malignant Melanoma and a Pitfall in Diagnosis: A Case Report and Review of the Literature.

Extramammary Paget disease (EMPD) is a rare intraepithelial carcinoma and an uncommon variant of Paget disease affecting areas of the apocrine-rich skin of the perineum, vulva, and less commonly, axilla. Women in their sixth to eighth decades are commonly affected. It is exceedingly rare for EMPD to present on the face, chest, abdomen, or other nonapocrine sites and even more unusual for EMPD to present as a pigmented lesion. The relationship between Paget cells in pigmented extramammary Paget disease (PEMPD) and reactive proliferation and colonization by melanocytes has been poorly explored. The relevance of this rare entity resides in its potential to be misdiagnosed clinically and histopathologically as malignant melanoma in situ. Therefore, application of a panel of immunostains and careful analysis and interpretation of these findings are essential to arrive at the correct diagnosis. We report a new case of PEMPD on a nonapocrine site. The specimen was examined by routine microscopy including hematoxylin and eosin stain as well as immunostains. Histologic examination revealed characteristic features of PEMPD confirmed with immunohistochemical stains.

Portable Skin Analyzers with Simultaneous Measurements of Transepidermal Water Loss, Skin Conductance and Skin Hardness.

Simultaneous measurement of skin physiological and physical properties are important for the diagnosis of skin diseases and monitoring of human performance, since it provides more comprehensive understanding on the skin conditions. Current skin analysis devices, however, require each of probes and unique protocols for the measurement of individual skin properties, resulting in inconvenience and increase of measurement uncertainty. This paper presents a pen-type skin analyzing device capable tomeasure three key skin properties at the same time: transepidermal water loss (TEWL), skin conductance, and skin hardness. It uses a single truncated hollow cone (THC) probe integrated with a humidity sensor, paired electrodes, and a load cell for the multimodal assessment of the skin properties. The present device measured TEWL with a sensitivity of 0.0068 (%/s)/(g/m2/h) and a linearity of 99.63%, conductance with a sensitivity of 1.02 µS/µS and a linearity of 99.36%, and hardness with a sensitivity of 0.98 Shore 00/Shore 00 and a linearity of 99.85%, within the appropriate ranges for the human skin. The present pen-type device has a high potential for the skin health diagnosis as well as the human performance monitoring applications.

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer.

Gastric cancer remains an unmet clinical problem in urgent need of newer and effective treatments. Here we show that the nuclear export protein, Exportin 1 (XPO1, chromosome region maintenance 1 or CRM1), is a promising molecular target in gastric cancer. We demonstrate significant overexpression of XPO1 in a cohort of histologically diverse gastric cancer patients with primary and metastatic disease. XPO1 RNA interference suppressed gastric cancer cell growth. Anti-tumor activity was observed with specific inhibitor of nuclear export (SINE) compounds (selinexor/XPOVIO), second-generation compound KPT-8602/eltanexor, KPT-185 and +ve control Leptomycin B in three distinct gastric cancer cell lines. SINE compounds inhibited gastric cancer cell proliferation, disrupted spheroid formation, induced apoptosis and halted cell cycle progression at the G1/S phase. Anti-tumor activity was concurrent with nuclear retention of tumor suppressor proteins and inhibition of colony formation. In combination studies, SINE compounds enhanced the efficacy of nab-paclitaxel in vitro and in vivo. More significantly, using non-coding RNA sequencing studies, we demonstrate for the first time that SINE compounds can alter the expression of non-coding RNAs (microRNAs and piwiRNAs). SINE treatment caused statistically significant downregulation of oncogenic miR-33b-3p in two distinct cell lines. These studies demonstrate the therapeutic significance of XPO1 in gastric cancer that warrants further clinical investigation.

High-resolution structure of a lytic polysaccharide monooxygenase from Hypocrea jecorina reveals a predicted linker as an integral part of the catalytic domain.

For decades, the enzymes of the fungus Hypocrea jecorina have served as a model system for the breakdown of cellulose. Three-dimensional structures for almost all H. jecorina cellulose-degrading enzymes are available, except for HjLPMO9A, belonging to the AA9 family of lytic polysaccharide monooxygenases (LPMOs). These enzymes enhance the hydrolytic activity of cellulases and are essential for cost-efficient conversion of lignocellulosic biomass. Here, using structural and spectroscopic analyses, we found that native HjLPMO9A contains a catalytic domain and a family-1 carbohydrate-binding module (CBM1) connected via a linker sequence. A C terminally truncated variant of HjLPMO9A containing 21 residues of the predicted linker was expressed at levels sufficient for analysis. Here, using structural, spectroscopic, and biochemical analyses, we found that this truncated variant exhibited reduced binding to and activity on cellulose compared with the full-length enzyme. Importantly, a 0.95-Å resolution X-ray structure of truncated HjLPMO9A revealed that the linker forms an integral part of the catalytic domain structure, covering a hydrophobic patch on the catalytic AA9 module. We noted that the oxidized catalytic center contains a Cu(II) coordinated by two His ligands, one of which has a His-brace in which the His-1 terminal amine group also coordinates to a copper. The final equatorial position of the Cu(II) is occupied by a water-derived ligand. The spectroscopic characteristics of the truncated variant were not measurably different from those of full-length HjLPMO9A, indicating that the presence of the CBM1 module increases the affinity of HjLPMO9A for cellulose binding, but does not affect the active site.

Safety and efficacy of the keystone and rhomboid flaps for immediate reconstruction after wide local excision of non-head and neck melanomas.

BACKGROUND: After wide local excision of cutaneous melanoma, large defects not amenable to simple primary closure are often covered with skin grafts. We report our experience using the rhomboid and keystone flaps to immediately close large axial and extremity wounds after potentially curative surgery for non-head and neck melanomas. METHODS: Between January 2011 and September 2016, demographic, operative, pathologic, and outcome data were prospectively collected on 60 patients who underwent wide local excision of melanoma followed by immediate flap reconstruction. Flaps were of either rhomboid or keystone type. Chi-square analysis was used to compare relationships between factors. RESULTS: All procedures were done by the senior author and as outpatient surgery. No patient required a surgical drain unless they were undergoing concomitant radical regional node dissection. Flap separation (arbitrarily defined as a >5-mm dehiscence of the suture line) occurred in 16/61 patients (26 %). No patient had flap loss. The risk of flap morbidity was significantly higher if the primary tumor was on the distal extremity-10 of 24 patients (42 %), all with keystone flaps-than if it was on the trunk or the proximal extremity (6/37 patients, 16 %), p = 0.04. There were no margins positive for either invasive or in situ melanoma in the entire cohort. CONCLUSIONS: Simple transposition flaps can successfully cover large defects after melanoma excision without the need for skin grafting. Keystone flaps in the distal extremity are more prone to separation, but this is minor and does not result in flap loss. There is minimal risk of a positive margin requiring flap takedown and a second re-excision.

Nanomanufacturing of 2D Transition Metal Dichalcogenide Materials Using Self-Assembled DNA Nanotubes.

2D transition metal dichalcogenides (TMDCs) are nanomanufactured using a generalized strategy with self-assembled DNA nanotubes. DNA nanotubes of various lengths serve as lithographic etch masks for the dry etching of TMDCs. The nanostructured TMDCs are studied by atomic force microscopy, photoluminescence, and Raman spectroscopy. This parallel approach can be used to manufacture 2D TMDC nanostructures of arbitrary geometries with molecular-scale precision.

Validation and implementation of a method for microarray gene expression profiling of minor B-cell subpopulations in man.

BACKGROUND: This report describes a method for the generation of global gene expression profiles from low frequent B-cell subsets by using fluorescence-activated cell sorting and RNA amplification. However, some of the differentiating compartments involve a low number of cells and therefore it is important to optimize and validate each step in the procedure. METHODS: Normal lymphoid tissues from blood, tonsils, thymus and bone marrow were immunophenotyped by the 8-colour Euroflow panel using multiparametric flow cytometry. Subsets of B-cells containing cell numbers ranging from 800 to 33,000 and with frequencies varying between 0.1 and 10 percent were sorted, subjected to mRNA purification, amplified by the NuGEN protocol and finally analysed by the Affymetrix platform. RESULTS: Following a step by step strategy, each step in the workflow was validated and the sorting/storage conditions optimized as described in this report. First, an analysis of four cancer cell lines on Affymetrix arrays, using either 100 ng RNA labelled with the Ambion standard protocol or 1 ng RNA amplified and labelled by the NuGEN protocol, revealed a significant correlation of gene expressions (r ≥ 0.9 for all). Comparison of qPCR data in samples with or without amplification for 8 genes showed that a relative difference between six cell lines was preserved (r ≥ 0.9). Second, a comparison of cells sorted into PrepProtect, RNAlater or directly into lysis/binding buffer showed a higher yield of purified mRNA following storage in lysis/binding buffer (p < 0.001). Third, the identity of the B-cell subsets validated by the cluster of differentiation (CD) membrane profile was highly concordant with the transcriptional gene expression (p-values <0.001). Finally, in normal bone marrow and tonsil samples, eight evaluated genes were expressed in accordance with the biology of lymphopoiesis (p-values < 0.001), which enabled the generation of a gene-specific B-cell atlas. CONCLUSION: A description of the implementation and validation of commercially available kits in the laboratory has been examined. This included steps for cell sorting, cell lysis/stabilization, RNA isolation, RNA concentration and amplification for microarray analysis. The workflow described in this report will enable the generation of microarray data from minor sorted B-cell subsets.

Superlative and Selective Sensing of Serotonin in Undiluted Human Serum Using Novel Polystyrene Sulfonate Conductive Polymer.

In the past 5 years, real-time health monitoring has become ubiquitous with the development of watches and rings that can measure and report on the physiological state. As an extension, real-time biomarker sensors, such as the continuous glucose monitor, are becoming popular for both health and performance monitoring. However, few real-time sensors for biomarkers have been made commercially available; this is primarily due to problems with cost, stability, sensitivity, selectivity, and reproducibility of biosensors. Therefore, simple, robust sensors are needed to expand the number of analytes that can be detected in emerging and existing wearable platforms. To address this need, we present a simple but novel sensing material. In short, we have modified the already popular PEDOT/PSS conductive polymer by completely removing the PEDOT component and thus have fabricated a polystyrene sulfonate (PSS) sensor electrodeposited on a glassy carbon (GC) base (GC-PSS). We demonstrate that coupling the GC-PSS sensor with differential pulse voltammetry creates a sensor capable of the selective and sensitive detection of serotonin. Notably, the GC-PSS sensor has a sensitivity of 179 µA µM-1 cm-2 which is 36x that of unmodified GC and an interferent-free detection limit of 10 nM, which is below the concentrations typically found in saliva, urine, and plasma. Notably, the redox potential of serotonin interfacing with the GC-PSS sensor is at -0.188 V versus Ag/AgCl, which is significantly distanced from peaks produced by common interferants found in biofluids, including serum. Therefore, this paper reports a novel, simple sensor and polymeric interface that is compatible with emerging wearable sensor platforms.

Gastric Cancer Survivorship: Multidisciplinary Management, Best Practices and Opportunities.

PURPOSE: Gastric cancer is the 5th most common malignancy worldwide. As early detection increases and treatments for gastric cancer improve, the number of gastric cancer survivors grows. METHODS: Here, we review the diagnosis and management of gastric cancer and discuss important considerations for gastric cancer survivorship including cancer surveillance, weight loss, malnutrition, fatigue, specific complications related to surgery and radiation, quality of life in gastric cancer survivorship, health behavior, and models of survivorship. RESULTS: Multimodality therapy with chemotherapy and surgery can result in chronic toxicities in multiple organ systems. This emphasizes the need for a multidisciplinary survivorship care model including cancer surveillance, management of chronic toxicities, and optimization of modifiable risk factors with long-term involvement of appropriate providers. CONCLUSION: Adequately caring for gastric cancer survivors requires a coordinated, multidisciplinary approach.

Long-term survival following adrenalectomy for secondary adrenal tumors: A systematic review and meta-analysis.

BACKGROUND: Secondary adrenal tumors (SATs) are uncommon, and the benefits of adrenalectomy for SATs have not been well-established. A systematic review and meta-analysis were conducted to assess the survival benefits of adrenalectomy for SATs. METHOD: ology: A systematic literature search was performed (1990-2022). The inclusion criteria included a known primary tumor with confirmed adrenal metastasis in patients who underwent adrenalectomy. The primary outcome was the overall survival (OS). RESULTS: A total of 26 studies were included, with 2279 patients. The average age at the time of diagnosis was 61.1 years. Lung cancer was the most common primary tumor. The average time from primary tumor diagnosis to identification of adrenal metastasis was 17 months. The median OS was 35.2 months. One, three, and five-year OS were 79.7 â€‹%, 49.1 â€‹%, and 37.9 â€‹%, respectively. CONCLUSION: The results of this review provide insight into the long-term survival of patients with SATs who underwent adrenalectomy. The study highlights the need for further research to identify the risk factors that play a role in the outcome of adrenalectomy in patients with SATs.

Spatial information outflow from the hippocampal circuit: distributed spatial coding and phase precession in the subiculum.

Hippocampal place cells convey spatial information through a combination of spatially selective firing and theta phase precession. The way in which this information influences regions like the subiculum that receive input from the hippocampus remains unclear. The subiculum receives direct inputs from area CA1 of the hippocampus and sends divergent output projections to many other parts of the brain, so we examined the firing patterns of rat subicular neurons. We found a substantial transformation in the subicular code for space from sparse to dense firing rate representations along a proximal-distal anatomical gradient: neurons in the proximal subiculum are more similar to canonical, sparsely firing hippocampal place cells, whereas neurons in the distal subiculum have higher firing rates and more distributed spatial firing patterns. Using information theory, we found that the more distributed spatial representation in the subiculum carries, on average, more information about spatial location and context than the sparse spatial representation in CA1. Remarkably, despite the disparate firing rate properties of subicular neurons, we found that neurons at all proximal-distal locations exhibit robust theta phase precession, with similar spiking oscillation frequencies as neurons in area CA1. Our findings suggest that the subiculum is specialized to compress sparse hippocampal spatial codes into highly informative distributed codes suitable for efficient communication to other brain regions. Moreover, despite this substantial compression, the subiculum maintains finer scale temporal properties that may allow it to participate in oscillatory phase coding and spike timing-dependent plasticity in coordination with other regions of the hippocampal circuit.