Giant thermal Hall conductivity in the pseudogap phase of cuprate superconductors.

The nature of the pseudogap phase of the copper oxides ('cuprates') remains a puzzle. Although there are indications that this phase breaks various symmetries, there is no consensus on its fundamental nature1. Fermi-surface, transport and thermodynamic signatures of the pseudogap phase are reminiscent of a transition into a phase with antiferromagnetic order, but evidence for an associated long-range magnetic order is still lacking2. Here we report measurements of the thermal Hall conductivity (in the x-y plane, κxy) in the normal state of four different cuprates-La1.6-xNd0.4SrxCuO4, La1.8-xEu0.2SrxCuO4, La2-xSrxCuO4 and Bi2Sr2-xLaxCuO6+δ. We show that a large negative κxy signal is a property of the pseudogap phase, appearing at its critical hole doping, p*. It is also a property of the Mott insulator at p ≈ 0, where κxy has the largest reported magnitude of any insulator so far3. Because this negative κxy signal grows as the system becomes increasingly insulating electrically, it cannot be attributed to conventional mobile charge carriers. Nor is it due to magnons, because it exists in the absence of magnetic order. Our observation is reminiscent of the thermal Hall conductivity of insulators with spin-liquid states4-6, pointing to neutral excitations with spin chirality7 in the pseudogap phase of cuprates.

Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.

Forearc carbon sink reduces long-term volatile recycling into the mantle.

Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.

Late-gestation prediction of outcome in tricuspid valve dysplasia and Ebstein's anomaly using fetal tricuspid regurgitation waveform analysis.

OBJECTIVE: To investigate the criteria, based on fetal TR waveforms in late gestation, to predict biventricular circulation (BV) after birth in cases of tricuspid valve dysplasia (TVD) or Ebstein's anomaly diagnosed during the fetal period. METHODS: We included 35 consecutive cases diagnosed with TVD or Ebstein's anomaly during the fetal period between January 2008 and December 2021 at Kanagawa Children's Medical Center, Kanagawa, Japan. The maximum velocity and change in pressure over time of tricuspid regurgitation (TR) jet (dP/dt), estimated using TR waveforms obtained during the late-gestation period (gestational age ≥ 28 weeks), were collected from patient records. dP/dt was calculated by dividing the change in estimated right ventricular pressure obtained using Bernoulli's principle by the time taken for the TR maximum velocity to change from one-third to two-thirds of its peak value. The outcome was divided into four categories: BV, single ventricular circulation, neonatal death and fetal death. Patients with BV were included in the BV group, while patients with single ventricular circulation, neonatal death or fetal death were included in the non-BV (NBV) group. RESULTS: Overall, 19 and 16 patients were included in the BV and NBV groups, respectively. The median TR maximum velocity was 3.3 (range, 2.4-3.6) m/s in the BV group and 1.9 (range, 1.0-3.3) m/s in the NBV group. There were no cases of postnatal BV in fetuses with TR maximum velocity < 2.4 m/s; cases with TR maximum velocity of 2.4-3.3 m/s were observed in both BV and NBV groups. Receiver-operating-characteristics-curve analysis was performed on the 11 patients in the BV group and five patients in the NBV group with a TR maximum velocity of 2.4-3.3 m/s. dP/dt ≥ 350 mmHg/s and TR maximum velocity ≥ 2.9 m/s were identified as criteria for predicting the outcome in such cases. The performance of dP/dt ≥ 350 mmHg/s in predicting BV after birth in fetuses with TVD or Ebstein's anomaly was higher compared to that of TR maximum velocity ≥ 2.9 m/s (sensitivity, 90.9% vs 72.3% and specificity, 80.0% vs 80.0%, respectively). CONCLUSIONS: In fetuses with TVD or Ebstein's anomaly, the postnatal outcome may be BV or NBV when the TR maximum velocity is 2.4-3.3 m/s. In such cases, by combining the TR maximum velocity with dP/dt ≥ 350 mmHg/s, BV after birth may be predicted with greater accuracy. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical characteristics and outcomes of pheochromocytoma crisis: a literature review of 200 cases.

PURPOSE: Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of internationally uniform and validated diagnostic criteria, pheochromocytoma crisis remains to be fully clarified. Therefore, we aimed to describe the clinical characteristics and outcomes of pheochromocytoma crisis through a literature review. METHODS: We performed a systematic literature search of PubMed/MEDLINE database, Igaku-Chuo-Zasshi (Japanese database), and Google Scholar to identify case reports of pheochromocytoma crisis published until February 5, 2021. Information was extracted and analyzed from the literature that reported adequate individual patient data of pheochromocytoma crisis in English or Japanese. Cases were also termed as pheochromocytoma multisystem crisis (PMC) if patients had signs of hyperthermia, multiple organ failure, encephalopathy, and labile blood pressure. RESULTS: In the 200 cases of pheochromocytoma crisis identified from 187 articles, the mean patient age was 43.8 ± 15.5 years. The most common symptom was headache (39.5%). The heart was the most commonly damaged organ resulting from a complication of a pheochromocytoma crisis (99.0%), followed by the lungs (44.0%) and the kidney (21.5%). PMC accounted for 19.0% of all pheochromocytoma crisis cases. After excluding 12 cases with unknown survival statuses, the mortality rate was 13.8% (26/188 cases). Multivariable logistic regression analysis revealed that nausea and vomiting were significantly associated with a higher mortality rate. CONCLUSION: Pheochromocytoma can present with different symptomatology, affecting different organ systems. Clinicians should be aware that patients with nausea or vomiting are at a higher risk of death because of pheochromocytoma crisis.

Calculation of an Enhanced A_{1g} Symmetry Mode Induced by Higgs Oscillations in the Raman Spectrum of High-Temperature Cuprate Superconductors.

In superconductors the Anderson-Higgs mechanism allows for the existence of a collective amplitude (Higgs) mode which can couple to eV light mainly in a nonlinear Raman-like process. The experimental nonequilibrium results on isotropic superconductors have been explained going beyond the BCS theory including the Higgs mode. Furthermore, in anisotropic d-wave superconductors strong interaction effects with other modes are expected. Here we calculate the Raman contribution of the Higgs mode from a new perspective, including many-body Higgs oscillations effects and their consequences in conventional, spontaneous Raman spectroscopy. Our results suggest a significant contribution to the intensity of the A_{1g} symmetry Raman spectrum in d-wave superconductors. In order to test our theory, we predict the presence of measurable characteristic oscillations in THz quench-optical probe time-dependent reflectivity experiments.

Preoperative oral care and effect on postoperative complications after major cancer surgery.

BACKGROUND: Improving patients' oral hygiene is an option for preventing postoperative pneumonia that may be caused by aspiration of oral and pharyngeal secretions. Whether preoperative oral care by a dentist can decrease postoperative complications remains controversial. A retrospective cohort study was undertaken to assess the association between preoperative oral care and postoperative complications among patients who underwent major cancer surgery. METHODS: The nationwide administrative claims database in Japan was analysed. Patients were identified who underwent resection of head and neck, oesophageal, gastric, colorectal, lung or liver cancer between May 2012 and December 2015. The primary outcomes were postoperative pneumonia and all-cause mortality within 30 days of surgery. Patient background was adjusted for with inverse probability of treatment weighting using propensity scoring. RESULTS: Of 509 179 patients studied, 81 632 (16·0 per cent) received preoperative oral care from a dentist. A total of 15 724 patients (3·09 per cent) had postoperative pneumonia and 1734 (0·34 per cent) died within 30 days of surgery. After adjustment for potential confounding factors, preoperative oral care by a dentist was significantly associated with a decrease in postoperative pneumonia (3·28 versus 3·76 per cent; risk difference - 0·48 (95 per cent c.i. -0·64 to-0·32) per cent) and all-cause mortality within 30 days of surgery (0·30 versus 0·42 per cent; risk difference - 0·12 (-0·17 to -0·07) per cent). CONCLUSION: Preoperative oral care by a dentist significantly reduced postoperative complications in patients who underwent cancer surgery.

Microscopic Investigation into the Electric Field Effect on Proximity-Induced Magnetism in Pt.

Electric field effects on magnetism in metals have attracted widespread attention, but the microscopic mechanism is still controversial. We experimentally show the relevancy between the electric field effect on magnetism and on the electronic structure in Pt in a ferromagnetic state using element-specific measurements: x-ray magnetic circular dichroism (XMCD) and x-ray absorption spectroscopy (XAS). Electric fields are applied to the surface of ultrathin metallic Pt, in which a magnetic moment is induced by the ferromagnetic proximity effect resulting from a Co underlayer. XMCD and XAS measurements performed under the application of electric fields reveal that both the spin and orbital magnetic moments of Pt atoms are electrically modulated, which can be explained not only by the electric-field-induced shift of the Fermi level but also by the change in the orbital hybridizations.

Collective bulk carrier delocalization driven by electrostatic surface charge accumulation.

In the classic transistor, the number of electric charge carriers--and thus the electrical conductivity--is precisely controlled by external voltage, providing electrical switching capability. This simple but powerful feature is essential for information processing technology, and also provides a platform for fundamental physics research. As the number of charges essentially determines the electronic phase of a condensed-matter system, transistor operation enables reversible and isothermal changes in the system's state, as successfully demonstrated in electric-field-induced ferromagnetism and superconductivity. However, this effect of the electric field is limited to a channel thickness of nanometres or less, owing to the presence of Thomas-Fermi screening. Here we show that this conventional picture does not apply to a class of materials characterized by inherent collective interactions between electrons and the crystal lattice. We prepared metal-insulator-semiconductor field-effect transistors based on vanadium dioxide--a strongly correlated material with a thermally driven, first-order metal-insulator transition well above room temperature--and found that electrostatic charging at a surface drives all the previously localized charge carriers in the bulk material into motion, leading to the emergence of a three-dimensional metallic ground state. This non-local switching of the electronic state is achieved by applying a voltage of only about one volt. In a voltage-sweep measurement, the first-order nature of the metal-insulator transition provides a non-volatile memory effect, which is operable at room temperature. Our results demonstrate a conceptually new field-effect device, extending the concept of electric-field control to macroscopic phase control.

Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.

BACKGROUND: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. METHODS: An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of ß-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. RESULTS: A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. CONCLUSION: Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

Discrepancies between multicriteria decision analysis-based ranking and intuitive ranking for pharmaceutical benefit-risk profiles in a hypothetical setting.

WHAT IS KNOWN AND OBJECTIVE: Multicriteria decision analysis (MCDA) has been generally considered a promising decision-making methodology for the assessment of drug benefit-risk profiles. There have been many discussions in both public and private sectors on its feasibility and applicability, but it has not been employed in official decision-makings. For the purpose of examining to what extent MCDA would reflect the first-hand, intuitive preference of evaluators in practical pharmaceutical assessments, we conducted a questionnaire survey involving the participation of employees of pharmaceutical companies. METHODS: Showing profiles of the efficacy and safety of four hypothetical drugs, each respondent was asked to rank them following the standard MCDA process and then to rank them intuitively (i.e. without applying any analytical framework). RESULTS AND DISCUSSION: These two approaches resulted in substantially different ranking patterns from the same individuals, and the concordance rate was surprisingly low (17%). Although many respondents intuitively showed a preference for mild, balanced risk-benefit profiles over profiles with a conspicuous advantage in either risk or benefit, the ranking orders based on MCDA scores did not reflect the intuitive preference. WHAT IS NEW AND CONCLUSION: Observed discrepancies between the rankings seemed to be primarily attributed to the structural characteristics of MCDA, which assumes that evaluation on each benefit and risk component should have monotonic impact on final scores. It would be difficult for MCDA to reflect commonly observed non-monotonic preferences for risk and benefit profiles. Possible drawbacks of MCDA should be further investigated prior to the real-world application of its benefit-risk assessment.

Clinical results of accelerated hypofractionated radiotherapy for central-type small lung tumours.

PURPOSE: We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. METHODS: Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5-3 Gy. A total dose of 69-75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan-Meier method. RESULTS: The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60-87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11-49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. CONCLUSIONS: Accelerated hypofractionated radiotherapy using a fraction size of 2.5-3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.

Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis.

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.

Preoperative chemoradiation therapy for esophageal cancer is a risk factor for the elevation of high mobility group box-1, leading to an increase in postoperative severe pulmonary complications.

We herein clarified the time course of changes in the serum high mobility group box chromosomal protein-1 (HMGB-1) concentrations in esophageal cancer patients after esophagectomy, and investigated whether the perioperative serum HMGB-1 levels correlate with the administration of neoadjuvant chemoradiation therapy (NACRT) and the postoperative clinical course, especially the occurrence of pulmonary complications, in such patients. Sixty patients who underwent right transthoracic esophagectomy for esophageal cancer were enrolled in this study. The relationship between the perioperative serum HMGB-1 levels and NACRT, and the postoperative severe pulmonary complications were evaluated. Patients with severe pulmonary complications (n = 44) tended to have undergone NACRT more often than those without severe pulmonary complications (n = 16). The preoperative and postoperative day 7 serum HMGB-1 concentrations were significantly higher in patients with severe pulmonary complications than those in patients without severe pulmonary complications. In the univariate and multivariate analyses, the use of NACRT and the preoperative elevations in the serum HMGB-1 levels (>4.2 ng/mL) were found to be significantly associated with pulmonary dysfunction. Furthermore, the response to NACRT was found to be significantly associated with the preoperative serum HMGB-1 levels. The use of NACRT contributes to preoperative serum HMGB-1 elevation, and these were risk factors for the occurrence of severe postoperative pulmonary complications in patients with esophageal cancer after thoracic esophagectomy.

Effect of 3-nitrooxypropanol on methane and hydrogen emissions, methane isotopic signature, and ruminal fermentation in dairy cows.

The objective of this crossover experiment was to investigate the effect of a methane inhibitor, 3-nitrooxypropanol (3NOP), on enteric methane emission, methane isotopic composition, and rumen fermentation and microbial profile in lactating dairy cows. The experiment involved 6 ruminally cannulated late-lactation Holstein cows assigned to 2 treatments: control and 3NOP (60 mg/kg of feed dry matter). Compared with the control, 3NOP decreased methane emission by 31% and increased hydrogen emission from undetectable to 1.33 g/d. Methane emissions per kilogram of dry matter intake and milk yield were also decreased 34% by 3NOP. Milk production and composition were not affected by 3NOP, except milk fat concentration was increased compared with the control. Concentrations of total VFA and propionate in ruminal fluid were not affected by treatment, but acetate concentration tended to be lower and acetate-to-propionate ratio was lower for 3NOP compared with the control. The 3NOP decreased the molar proportion of acetate and increase those of propionate, butyrate, valerate, and isovalerate. Deuterium-to-hydrogen ratios of methane and the abundance of (13)CH3D were similar between treatments. Compared with the control, minor (4‰) depletion in the (13)C/(12)C ratio was observed for 3NOP. Genus composition of methanogenic archaea (Methanobrevibacter, Methanosphaera, and Methanomicrobium) was not affected by 3NOP, but the proportion of methanogens in the total cell counts tended to be decreased by 3NOP. Prevotella spp., the predominant bacterial genus in ruminal contents in this experiment, was also not affected by 3NOP. Compared with the control, Ruminococcus and Clostridium spp. were decreased and Butyrivibrio spp. was increased by 3NOP. This experiment demonstrated that a substantial inhibition of enteric methane emission by 3NOP in dairy cows was accompanied with increased hydrogen emission and decreased acetate-to-propionate ratio; however, neither an effect on rumen archaeal community composition nor a significant change in the isotope composition of methane was observed.

Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia.

Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.

Hydrogen sulphide increases hepatic differentiation of human tooth pulp stem cells compared with human bone marrow stem cells.

AIM: To determine the differences in stem cell properties, in hepatic differentiation and in the effects of hydrogen sulphide (H2 S) on hepatic differentiation between human bone marrow stem cells (hBMC) and stem cells from human exfoliated primary tooth pulp (SHED). METHODOLOGY: CD117(+) cells were magnetically separated and subjected to hepatic differentiation. CD117(+) cell lineages were characterized for transcription factors indicative of stem cells by qRT-PCR. For the last 9 days of the differentiation, the test cells were exposed to 0.1 ng mL(-1) H2 S. Immunocytochemistry and flow cytometry of albumin, alpha-fetoprotein and carbamoyl phosphate synthetase were carried out after differentiation. Urea concentration and glycogen synthesis were also determined. RESULTS: Genes expressed in SHED were also expressed in BMC. No difference in expression level of hepatic markers was shown by immunofluorescence. SHED showed more positive cells than hBMC (P < 0.01). H2 S increased the number of positive cells in both cultures (P < 0.01). Urea concentration and glycogen synthesis increased significantly after H2 S exposure (P < 0.001 and P < 0.05, respectively). Real-time PCR data were analysed by RT(2) profiler RT-PCR Array Data Analysis version 3.5 (Qiagen), and ELISA data were analysed by Bonferroni's multiple comparison using Windows spss version 16 (SPSS Inc, Chicago, IL, USA). Bonferroni's multiple comparison test was also carried out after angle transformation for the percentage data of flow cytometer using Windows spss(®) version 16 (SPSS Inc). Statistical significance was accepted at P < 0.05. CONCLUSIONS: Stem cells from human exfoliated primary tooth pulp and BMC have similar properties. The level of hepatic differentiation in SHED compared with BMC was the same or higher. H2 S increased the level of hepatic differentiation.

Abundant FUS-immunoreactive pathology in the skin of sporadic amyotrophic lateral sclerosis.

OBJECTIVES: The fused in sarcoma (FUS) protein is a 526 amino acid and its expression is ubiquitous. Recently, mutations in a gene coding FUS have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic forms of ALS, suggesting that FUS has an important role in the neurodegeneration occurring in sporadic disease. However, there has been no study of FUS in ALS skin. MATERIAL AND METHODS: We made a quantitative immunohistochemical study of the expression of FUS in the skin from patients with sporadic ALS and controls. RESULTS: The proportion of FUS-immunoreactive (ir) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.78, P < 0.001) between the proportion and duration of illness in ALS patients. The optical density of FUS-ir cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.49, P < 0.05) between the immunoreactivity and duration of illness in ALS patients. CONCLUSIONS: These data suggest that changes of FUS in ALS skin are related to the disease process, and that metabolic alterations of FUS may take place in the skin of patients with ALS.