Impact of Lighting Assessment and Optimization on Participation and Quality of Life in Individuals with Vision Loss.

This pilot study was designed to investigate the effects of a holistic lighting intervention on the quality of life for individuals with low vision. Sixty participants (44 women; median age 69 years) with visual impairment received lighting interventions, including a home visit and consultation in a lighting lab. Assisted by low vision consultants, participants evaluated their performance using the Canadian Occupational Performance Measure (COPM) before and after the intervention. Improvements in visual functioning and quality of life were evaluated using the 39-item National Eye Institute Visual Function Questionnaire (NEI VFQ-39), the Groffman Visual Tracing Test, and the Farnsworth Dichotomous Test (D15). Following the lighting intervention, scores improved for all activities in the COPM (p < 0.01), for near activities and vision-specific role difficulties in the VFQ-39 (p < 0.05), and overall in the D15 test (p < 0.05). These results suggest the intervention provided an effective method for improving the participants' quality of life and performance.

Circadian rhythm of markers of bone turnover in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) have a high risk of bone fractures. A circadian rhythmicity in turnover and mineralization of bone appears to be of importance for bone health. In CKD disturbances in the circadian rhythm of various functions has been demonstrated and indeed the circadian rhythm in the mineral metabolism is disturbed. The aim of the present study was to compare the circadian rhythm of bone turnover markers in ten patients with CKD to ten healthy controls. Bone turnover markers (C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase 5b, N-terminal propeptide of type I procollagen, bone alkaline phosphatase and osteocalcin) were measured every third hour for 24 h. All bone turnover markers displayed a significant circadian rhythm in both groups and there were no significant differences in the rhythmicity between the two groups (no group*time interaction). As expected, due to the reduced renal clearance, the overall level of C-terminal telopeptide of type I collagen and osteocalcin was higher in CKD compared to the healthy controls. The present study suggests that disturbances in the circadian rhythm of bone turnover do not explain the metabolic bone disease and increased risk of fractures in CKD.

Trade-offs among transport, support, and storage in xylem from shrubs in a semiarid chaparral environment tested with structural equation modeling.

The xylem in plants is specialized to transport water, mechanically support the plant body, and store water and carbohydrates. Balancing these functions leads to trade-offs that are linked to xylem structure. We proposed a multivariate hypothesis regarding the main xylem functions and tested it using structural equation modeling. We sampled 29 native shrub species from field sites in semiarid Southern California. We quantified xylem water transport (embolism resistance and transport efficiency), mechanical strength, storage of water (capacitance) and starch, minimum hydrostatic pressures (Pmin), and proportions of fibers, vessels, and parenchyma, which were treated as a latent variable representing "cellular trade-offs." We found that xylem functions (transport, mechanical support, water storage, and starch storage) were independent, a result driven by PminPmin was strongly and directly or indirectly associated with all xylem functions as a hub trait. More negative Pmin was associated with increased embolism resistance and tissue strength and reduced capacitance and starch storage. We found strong support for a trade-off between embolism resistance and transport efficiency. Tissue strength was not directly associated with embolism resistance or transport efficiency, and any associations were indirect involving Pmin With Pmin removed from the model, cellular trade-offs were central and related to all other traits. We conclude that xylem traits are broadly governed by functional trade-offs and that the Pmin experienced by plants in the field exerts a strong influence over these relationships. Angiosperm xylem contains different cell types that contribute to different functions and that underpin trade-offs.

Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial).

BACKGROUND: There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS: In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS: Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION: HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.

ANTECEDENTES: Se dispone de poca información sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante. MÉTODOS: En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5-Fluorouracilo 750 mg/m2 /infusión de 24 horas en los días 1-5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ-C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad. RESULTADOS: De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT. CONCLUSIÓN: La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.

Motor unit number index and compound muscle action potential amplitude.

OBJECTIVES: MUNIX (motor unit number index), derived from the compound muscle action potential (CMAP) and surface EMG interference pattern (SIP) has become popular as a substitute for motor unit number estimation (MUNE). This study was undertaken to determine why, in recent recordings from amyotrophic lateral sclerosis (ALS) patients and healthy controls, we found that MUNIX values resembled CMAP amplitudes more closely than MUNE values. METHODS: The relationship between MUNIX and CMAP and SIP amplitudes was investigated by a theoretical analysis and by reanalysing the data from the previous study. RESULTS: Theory indicates that when motor unit potentials overlap extensively, information about motor unit size and number is lost, and MUNIX depends only on CMAP area and power. Accordingly, MUNIX values were found to be sensitive to changes in CMAP amplitude but insensitive to changes in SIP amplitude. The reproducibility of MUNIX measurements in healthy controls was found to depend almost entirely on correlation with CMAP properties. CONCLUSIONS: MUNIX gives misleading information about motor unit numbers in healthy controls, and provides little information about loss of motor units in ALS patients beyond that given by simple CMAP amplitude measurements. SIGNIFICANCE: MUNIX should not be interpreted as a MUNE method.

Effects of neoadjuvant chemoradiotherapy vs chemotherapy alone on the relief of dysphagia in esophageal cancer patients: secondary endpoint analysis in a randomized trial.

Dysphagia is the most significant symptom in patients with esophageal cancer. There are different therapeutic interventions designed to relieve dysphagia, but few studies have addressed the effects of neoadjuvant therapy. The aim of this study is to compare the effects on dysphagia of neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) and further to study the association between dysphagia response and histological response. Patient reported swallowing function was a secondary endpoint in the NeoRes trial, in which patients were randomized between neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Patients completed dysphagia questionnaires before the start and after neoadjuvant therapy, using the European Organization for Research and Treatment of Cancer (EORTC) esophageal cancer modules QLQ-OES24/OG25. Chirieac tumor regression grade (TRG) was used to assess the histological response. Out of 181 patients were randomized, of whom 87% completed the dysphagia questionnaires before and 73% after neoadjuvant treatment. Patient characteristics were similar between the treatment arms. Among patients reporting dysphagia at baseline, neoadjuvant therapy improved dysphagia in both arms. The mean dysphagia score after neoadjuvant treatment was significantly lower after nCT compared to after nCRT (P = 0.022). The reported dysphagia did not differ between those with a complete histological response (TRG 1) and those without any response at all (TRG 4) (P = 0. 583).

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Velocity-space tomography using prior information at MAST.

Velocity-space tomography provides a way of diagnosing fast ions in a fusion plasma by combining measurements from multiple instruments. We use a toroidally viewing and a vertically viewing fast-ion D-alpha diagnostic installed on the mega-amp spherical tokamak (before the upgrade) to perform velocity-space tomography of the fast-ion distribution function. To make up for the scarce amount of data, prior information is included in the inversions. We impose a non-negativity constraint, suppress the distribution in the velocity-space region associated with null-measurements, and encode the belief that the distribution function does not extend to energies significantly higher than those expected neoclassically. This allows us to study the fast-ion velocity distributions and the derived fast-ion densities before and after a sawtooth crash.

Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.

Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity. SUMMARY: Background Factor VII-activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low-frequency missense variant Marburg-I (rs7080536) in the FSAP-encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome-wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene-based tests. Using GWAS, we confirmed the strong association between the Marburg-I variant and FSAP activity. HABP2 was also significant in the gene-based analysis, and remained significant after exclusion of Marburg-I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg-I carriers, and this finding was replicated. A secondary genome-wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg-I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.

Beam-Ion Acceleration during Edge Localized Modes in the ASDEX Upgrade Tokamak.

The acceleration of beam ions during edge localized modes (ELMs) in a tokamak is observed for the first time through direct measurements of fast-ion losses in low collisionality plasmas. The accelerated beam-ion population exhibits well-localized velocity-space structures which are revealed by means of tomographic inversion of the measurement, showing energy gains of the order of tens of keV. This suggests that the ion acceleration results from a resonant interaction between the beam ions and parallel electric fields arising during the ELM. Orbit simulations are carried out to identify the mode-particle resonances responsible for the energy gain in the particle phase space. The observation motivates the incorporation of a kinetic description of fast particles in ELM models and may contribute to a better understanding of the mechanisms responsible for particle acceleration, ubiquitous in astrophysical and space plasmas.

The utility of motor unit number estimation methods versus quantitative motor unit potential analysis in diagnosis of ALS.

OBJECTIVE: To compare the diagnostic utility of motor unit number estimation (MUNE) methods to motor unit potential (MUP) analysis in amyotrophic lateral sclerosis (ALS). METHODS: Twenty-five patients (1 definite, 11 probable, 9 possible ALS and 4 progressive muscular atrophy) and 22 healthy controls were prospectively included. Quantitative MUP analysis and three MUNE methods; Multiple Point Stimulation MUNE (MPS), Motor Unit Number Index (MUNIX) and MScanFit MUNE (MScan) were done in abductor pollicis brevis muscle. The sensitivities were compared by McNemar chi-square test. MUNE, MUP and revised ALS Functional Rating Scale (ALSFRS-R) parameters were correlated by regression analysis. RESULTS: The sensitivities of MPS (76%) and MScan (68%) were higher than MUP duration (36%) and amplitude (40%) in detecting motor unit loss (p < 0.05). MUNE methods increased the categorical probability from possible to probable ALS in 4 patients (16%). There was only significant correlation between ALSFRS-R and MScan (r = 0.443, p = 0.027) among the electrophysiological tests. MUNE methods did not correlate to MUP parameters. CONCLUSIONS: MUNE methods are more sensitive in showing abnormality than MUP analysis. SIGNIFICANCE: MUNE methods, in particular MScan, may have the potential to be implemented in the clinical practice for diagnosis and follow-up of neuromuscular disorders particularly ALS.

Velocity-space sensitivities of neutron emission spectrometers at the tokamaks JET and ASDEX Upgrade in deuterium plasmas.

Future fusion reactors are foreseen to be heated by the energetic alpha particles produced in fusion reactions. For this to happen, it is important that the energetic ions are sufficiently confined. In present day fusion experiments, energetic ions are primarily produced using external heating systems such as neutral beam injection and ion cyclotron resonance heating. In order to diagnose these fast ions, several different fast-ion diagnostics have been developed and implemented in the various experiments around the world. The velocity-space sensitivities of fast-ion diagnostics are given by so-called weight functions. Here instrument-specific weight functions are derived for neutron emission spectrometry detectors at the tokamaks JET and ASDEX Upgrade for the 2.45 MeV neutrons produced in deuterium-deuterium reactions in deuterium plasmas. Using these, it is possible to directly determine which part of velocity space each detector observes.

Reproducibility, and sensitivity to motor unit loss in amyotrophic lateral sclerosis, of a novel MUNE method: MScanFit MUNE.

OBJECTIVE: To examine inter- and intra-rater reproducibility and sensitivity to motor unit loss of a novel motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), compared to two traditional MUNE methods; Multiple point stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX). METHODS: Twenty-two ALS patients and 20 sex- and age-matched healthy controls were included. MPS, MUNIX, and MScan were performed twice each by two blinded physicians. Reproducibility of MUNE values was assessed by coefficient of variation (CV) and intra class correlation coefficient (ICC). Ability to detect motor unit loss was assessed by ROC curves and area under the curve (AUC). The times taken for each of the methods were recorded. RESULTS: MScan was more reproducible than MPS and MUNIX both between and within operators. The mean CV for MScan (12.3%) was significantly lower than for MPS (24.7%) or MUNIX (21.5%). All methods had ICC>0.94. MScan and Munix were significantly quicker to perform than MPS (6.3mvs. 13.2m). MScan (AUC=0.930) and MPS (AUC=0.899) were significantly better at discriminating between patients and healthy controls than MUNIX (AUC=0.831). CONCLUSIONS: MScan was more consistent than MPS or MUNIX and better at distinguishing ALS patients from healthy subjects. SIGNIFICANCE: MScan may improve detection and assessment of motor unit loss.

Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus.

Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30-40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003-2009, and from 353 controls. All samples were analysed for anti-ß2 glycoprotein 1 (anti-ß2GP1) and anticardiolipin antibodies (aCL), C-reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90 mg/l; P < 0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P = 0.665). Median C3 levels were similar in cases (1.03 g/l) and controls (1.00 g/l), whereas median C4 levels were 0.16 g/l in cases versus. 0.19 in controls (P < 0.0001). However, aPL-positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07 g/l; P = 0.001) and C4 levels (0.11 versus 0.16 g/l; P < 0.0001) compared to aPL-negative patients. Lower C3 and C4 values in aPL-positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL-positive SLE patients compared to SLE patients without aPL.

Medication use and drug-related problems among women at maternity wards-a cross-sectional study from two Norwegian hospitals.

PURPOSE: There is a lack of knowledge about drug-related problems (DRPs) among pregnant and lactating women. The aim of this study was to determine the extent and type of DRPs among pregnant and lactating women in the maternity ward at two Norwegian hospitals. We also aimed to investigate which drugs were involved in the identified DRPs, and the outcome of solving the DRPs. METHODS: Patient-reported treatment reviews were performed to assess the prevalence and type of DRPs among women at the two maternity wards. RESULTS: In all, 212 women were included in the study, of which 89 (42 %) had experienced at least one DRP (105 DRPs in total). "Need for additional drug" (49 cases, 46.7 %) was the most frequent. The most frequent drug group involved in DRPs was drugs acting on the respiratory system, and the most common intervention was raising awareness/providing confidence/giving information during the patient-reported treatment review. CONCLUSIONS: Over four out of ten women in the maternity wards have DRPs, and many have questions about drug use during pregnancy and lactation. Many of the DRPs could probably be avoided by providing patient-reported treatment reviews to pregnant women as a part of antenatal care. Multidisciplinary collaboration including physicians, midwifes, and pharmacists in antenatal care and in maternity ward could possibly prevent DRPs and thereby promote patient safety for pregnant and lactating women.

A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction.

BACKGROUND: Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT. PATIENTS AND METHODS: This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm. RESULTS: The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms. CONCLUSION: The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival. CLINICALTRIALSGOV: NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death.

Necroptosis is a caspase-independent form of regulated cell death that has been implicated in the development of a range of inflammatory, autoimmune and neurodegenerative diseases. The pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), is the most terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by Receptor Interacting Protein Kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. However, the molecular interactions governing the processes downstream of RIPK3 activation remain poorly defined. Using a phenotypic screen, we identified seven heat-shock protein 90 (HSP90) inhibitors that inhibited necroptosis in both wild-type fibroblasts and fibroblasts expressing an activated mutant of MLKL. We observed a modest reduction in MLKL protein levels in human and murine cells following HSP90 inhibition, which was only apparent after 15 h of treatment. The delayed reduction in MLKL protein abundance was unlikely to completely account for defective necroptosis, and, consistent with this, we also found inhibition of HSP90 blocked membrane translocation of activated MLKL. Together, these findings implicate HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3.