A New Criterion for Determining a Cutoff Value Based on the Biases of Incidence Proportions in the Presence of Non-differential Outcome Misclassifications.

When conducting database studies, researchers sometimes use an algorithm known as "case definition," "outcome definition," or "computable phenotype" to identify the outcome of interest. Generally, algorithms are created by combining multiple variables and codes, and we need to select the most appropriate one to apply to the database study. Validation studies compare algorithms with the gold standard and calculate indicators such as sensitivity and specificity to assess their validities. As the indicators are calculated for each algorithm, selecting an algorithm is equivalent to choosing a pair of sensitivity and specificity. Therefore, receiver operating characteristic curves can be utilized, and two intuitive criteria are commonly used. However, neither was conceived to reduce the biases of effect measures (e.g., risk difference and risk ratio), which are important in database studies. In this study, we evaluated two existing criteria from perspectives of the biases and found that one of them, called the Youden index always minimizes the bias of the risk difference regardless of the true incidence proportions under nondifferential outcome misclassifications. However, both criteria may lead to inaccurate estimates of absolute risks, and such property is undesirable in decision-making. Therefore, we propose a new criterion based on minimizing the sum of the squared biases of absolute risks to estimate them more accurately. Subsequently, we apply all criteria to the data from the actual validation study on postsurgical infections and present the results of a sensitivity analysis to examine the robustness of the assumption our proposed criterion requires.

CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society.

BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. METHODS: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. RESULTS: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). CONCLUSIONS: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

Improvement of Functional Outcomes in Patients with Stroke who Received Alteplase for Over 15 Years: Japan Stroke Data Bank.

AIM: The nationwide verification of intravenous thrombolysis (IVT) was rarely performed after the extension of the therapeutic time window of alteplase or after the expansion of mechanical thrombectomy (MT). We aimed to examine the long-term change in accurate real-world outcomes of IVT in patients with acute ischemic stroke (AIS) using the Japan Stroke Databank, a representative Japan-wide stroke database. METHODS: We extracted all patients with AIS who received IVT with alteplase between October 11, 2005, the approval date for alteplase use for AIS in Japan, and December 31, 2020. Patients were categorized into three groups using two critical dates in Japan as cutoffs: the official extension date of the therapeutic time window for IVT to within 4.5 h of symptom onset and the publication date of the revised guideline, where the evidence level of MT was heightened. We assessed the yearly trend of IVT implementation rates and the secular changes and three-group changes in clinical outcomes at discharge. RESULTS: Of 124,382 patients with AIS, 9,569 (7.7%) received IVT (females, 41%; median age, 75 years). The IVT implementation rate has generally increased over time and plateaued in recent years. The proportion of favorable outcomes (modified Rankin Scale score of 0-2) increased yearly over 15 years. The results of the changes in the outcomes of the three groups were similar to those of the annual changes. CONCLUSIONS: We revealed that IVT implementation rates in patients with AIS increased, and the functional outcome in these patients improved over 15 years. Therefore, the Japanese IVT dissemination strategy is considered appropriate and effective.

Severe Macular Ischemia Is Associated with a Poor Visual Prognosis and Serious Complications in Eyes with Central Retinal Vein Occlusion.

PURPOSE: This study aims to investigate the factors influencing post-treatment visual acuity (VA) in patients with central retinal vein occlusion (CRVO) with macular edema (ME). METHODS: The subjects of this study were patients who visited our clinic from May 2013 to July 2019 and who could be followed up with for at least 12 months. Cases with hemi CRVO were excluded from this study. Factors considered in the evaluation of visual prognosis at the 12 months included initial best-corrected VA, central subfoveal thickness, CRVO subtype (nonischemic, ischemic, or converted from nonischemic to ischemic), time taken for the first treatment, number of anti-vascular endothelial growth factor agent injections, structural changes in the inner and outer retinal layers, and the presence of macular ischemia in a multiple regression analysis. RESULTS: There were 41 patients with 41 eyes, 27 males and 14 females. The mean age of the patients was 70.5 ± 12.2 (mean ± standard deviation) years. The mean VA was 0.544 ± 0.576, 0.456 ± 0.568, and 0.586 ± 0.665 at the initial visit, 12 months later, and time of last observation, respectively. There were no significant differences in VAs observed between the baseline, month 12, and final visit. Multiple regression analysis revealed that the external limiting membrane score at month 12 (p = 0.030), the VA at initial visit (p < 0.001), and the presence of severe macular ischemia (p < 0.001) were the key factors associated with VA at month 12. Moreover, severe macular ischemia was identified as the only factor affecting decimal VA less than 20/200 at the last observation (p = 0.0092). CONCLUSIONS: Severe macular ischemia is strongly linked to a poor visual prognosis in patients with ME associated with CRVO.

Conceptual study on extraction of formic acid from the electrolyte after electroreduction of CO2: Desalination and dehydration using a high-silica chabazite zeolite membrane.

Here, we propose a two-step pervaporation system with a high-silica CHA (chabazite) membrane, which has sufficient resistance to water and acid, to demonstrate the extraction and condensation of the formic acid formed by electroreduction of CO2. The kinetic diameters of water and formic acid are similar and smaller than the pore size of CHA, while the hydrated electrolyte ions (e.g., K+ and Cl-) are larger than the pore size of CHA. Consequently, the electrolyte ions are separated from the mixture of water and formic acid in the first desalination process, and then water molecules are easily removed from the mixture in the second dehydration process. From 300 ml of an approximately 3 wt% formic acid aqueous solution containing 0.5 M KCl, 10 ml of 18.2 wt% formic acid was obtained.

Synergistic effect of Ag decorated in-liquid plasma treated titanium dioxide catalyst for efficient electrocatalytic CO2 reduction application.

Recently, the conversion of carbon dioxide (CO2) into a useful resource and its byproducts by electrocatalytic reduction has been studied. It is well known that CO2 can be selectively reduced by gold, lead, etc. supported on conductive carbon. However, the high pH in the vicinity of the electrode raises concerns about the catalyst and catalyst support degradation. Therefore, we considered that using chemically stable TiO2 (titanium dioxide) powder as an alternative to carbon. Surface treatment using in-liquid plasma was used to improve the electrochemical properties of TiO2. TiO2 maintained its particle shape and crystalline structure after in-liquid plasma treatment. Electrochemical properties were evaluated and the disappearance of Ti4+ and Ti3+ redox peaks derived from TiO2 and a decrease in hydrogen overvoltage were observed. The hydrogen overvoltage relationship suggested that tungsten coating or doping on a portion of the reduced TiO2 surface. Electrocatalytic CO2 reduction using the silver nanoparticle-supported in-liquid plasma treated TiO2 showed increased hydrogen production. In electrocatalytic CO2 reduction, the ratio of hydrogen to carbon monoxide gas is important. Therefore, in-liquid plasma treated TiO2 is useful for the electrocatalytic CO2 reduction application.

Long-Term Prognosis of Patients with Polypoidal Choroidal Vasculopathy Treated with Photodynamic Therapy.

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases.

Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery.

iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

Submucosal Injection Using Epinephrine-Added Saline in Cold Snare Polypectomy for Colorectal Polyps Shortens Time Required for Resection: A Randomized Controlled Study.

AIMS: Immediate bleeding after cold snare polypectomy (CSP) for colorectal polyps might interfere with confirmation of residuals and prolong the time required for resection. We investigated whether submucosal epinephrine-added saline injection reduces the time required for the CSP procedure. METHODS: We conducted a single-center, prospective, randomized controlled trial (clinical trial registration number: UMIN000046770). Patients with colorectal polyps ≤ 10 mm were randomly allocated to either CSP with epinephrine-added submucosal injection (CEMR group) or conventional CSP (CSP group). The primary outcome was the time required for resection defined as the time from the initiation of resection (the first insertion of the snare in the CSP group or the injection needle in the CEMR group) to the end of resection (confirming complete resection endoscopically after recognizing the cessation of immediate bleeding) in each lesion, and the secondary outcome was the time to spontaneous cessation of immediate bleeding after resection defined as the time from ensnaring the lesion to confirming the spontaneous cessation of immediate bleeding. RESULTS: A total of 126 patients were randomly assigned. Finally, 261 lesions in 118 patients (CEMR group, n = 59; CSP group, n = 59) were analyzed. The time required for resection calculated using the least-square mean was significantly shorter in the CEMR group (106.3 s, 95% CI 97.5 to 115.4 s) than in the CSP group (130.9 s, 95% CI 121.2 to 140.7 s) (P < 0.001). The time to spontaneous cessation of immediate bleeding was also significantly shorter in the CEMR group (20.4 s, 95% CI 14.3 to 26.5 s) than in the CSP group (74.2 s, 95% CI 67.6 to 80.7 s) (P < 0.001). Neither group had cases requiring hemostasis, perforation, or delayed bleeding. CONCLUSIONS: CEMR shortened the time for resection by shortening the time to cessation of immediate bleeding compared with conventional CSP in colorectal polyps ≤ 10 mm.

Interfacial molecular regulation of TiO2 for enhanced and stable cocatalyst-free photocatalytic hydrogen production.

On the basis of the inherent property limitations of commercial P25-TiO2, many surface interface modification methods have attracted substantial attention for further improving the photocatalytic properties. However, current strategies for designing and modifying efficient photocatalysts (which exhibit complicated manufacturing processes and harsh conditions) are not efficient for production that is low cost, is nontoxic, and exhibits good stability; and therefore restrict practical applications. Herein, a facile and reliable method is reported for in situ amine-containing silane coupling agent functionalization of commercial P25-TiO2 by covalent surface modification for constructing a highly efficient photocatalyst. As a consequence, a high efficiency of H2 evolution was achieved for TiO2-SDA with 0.95 mmol h-1 g-1 (AQE ∼45.6 % at 365 nm) under solar light irradiation without a co-catalyst. The amination modification broadens the light absorption range of the photocatalyst, inhibits the binding of photogenerated carriers, and improves the photocatalytic efficiency; which was verified by photochemical properties and DFT theoretical calculations. This covalent modification method ensures the stability of the photocatalytic reaction. This work provides an approach for molecularly modified photocatalysts to improve photocatalytic performance by covalently modifying small molecules containing amine groups on the photocatalyst surface.

Enhanced degradation of ibuprofen using a combined treatment of plasma and Fenton reactions.

Advanced oxidation technologies (AOTs) proved to be effective in the degradation of hazardous organic impurities like acids, dyes, antibiotics etc. in the last few decades. AOTs are mainly based on the generation of reactive chemical species (RCS) such as hydroxyl, superoxide radicals etc., which plays an important role in the degradation of organiccompounds. In this work, plasma supported AOT i.e. Fenton reactions have been applied for the degradation of ibuprofen. As compared to traditional AOTs plasma assisted AOT is technologically superior due to its capability to produce RCS at a controlled rate without using chemical agents. This process work at normal room temperature and pressure. Herein, we optimized better operating conditions to generate good plasma discharge and hydroxyl radicals based on critical parameters, including frequency, pulse width and different gases like O2, Ar etc. Also, the one-pot carbonization method is used for the synthesis of Fe-based ordered mesoporous carbon (OMC) as a heterogeneous catalyst for the Fenton reactions. Using plasma-supported Fenton reactions, 88.3 % degradation efficiency is achieved using Fe-OMC catalyst for the ibuprofen degradation. Also, the mineralization of the ibuprofen is studied using total organic carbon (TOC) analysis.

AUTOLOGOUS POSTERIOR CAPSULE FLAP TRANSPLANTATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE IN A PSEUDOPHAKIC EYE.

PURPOSE: To report a case of refractory macular hole (MH) in pseudophakic eye treated with autologous posterior capsule flaps transplantation. METHODS: Case report. RESULTS: A 48-year-old man visited our hospital with visual loss in the right eye because of unclosed MH. The patient had undergone two previous surgeries in another hospital, that is, the first included a cataract surgery, vitrectomy, and internal limiting membrane peeling with sulfur hexafluoride (SF 6 ) gas tamponade, and the second included an ineffective autologous internal limiting membrane flap technique and massaging the edges of the MH with a soft-tipped flute needle followed by the same gas, but the MH remained open. In our hospital, posterior capsule flaps were acquired from the same eye, inserted into the MH, and the same gas tamponade was performed, which was about four months after the disease onset (3 months after the prior second surgery). The patient kept face-down position for a week after the surgery and the MH was closed, which remained for over 12 months. The visual acuity improved from 20/250 to 20/60, and the retinal sensitivities around the MH gradually improved. CONCLUSION: An autologous posterior capsule flaps transplantation was effective in the management of refractory MH to not only close the MH but also improve the visual outcomes.

Interactions between pH, reactive species, and cells in plasma-activated water can remove algae.

Lightning strikes cause nitrogen to dissolve in water and form reactive nitrogen and oxygen species, which form natural fertilizers that can be absorbed through plant roots. Such processes during rainstorm events can be simulated by applying plasma to a solution. Plasma-activated water (PAW) has great potential as a source of various dissolved reactive chemical species. Different mixtures of species are produced using different solution compositions. Here, basil seeds were grown in PAW to prevent blooms of Chlorella vulgaris and ion chromatography and UV-vis spectroscopy were used to quantify reactive ions. NO2 -, NO3 -, and H2O2 were found to be key to the antialgal effect. Secondary reactive ions such as peroxynitrite (ONOO-, ONOOH) were also involved. The antialgal effect was strongly related to the pH around the algal cells. Acidification was predominantly caused by the generation of NO2 - and H2O2. After two weeks monitoring basil growth, the antifungal properties were preserved, few reactive oxygen species formed in the plasma zone, and only reactive nitrogen species were transformed into reactive peroxynitrite ions. The pH around the cells was determined using an iridium oxide microelectrode. The PAW antialgal mechanism depended on acidic conditions (pH 2.2, at which peroxynitrite can be generated) under which ONOOH penetrated the algal cell membranes, destroying the cells and preventing growth. This practical and sustainable PAW process allows a surprising amount of fertilizer to be generated with an antialgal effect that could be used in various eco-friendly agricultural processes under ambient conditions.

[The questionnaire survey regarding the impact of COVID-19 pandemic on Parkinson's disease patients].

We conducted the multicenter questionnaire survey targeting patients with Parkinson's disease (PD) in order to investigate the impacts on their daily lives and their requests to hospitals in the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mainly using open-ended questionnaire, we asked their anxiety, troubles they are facing, and requests toward hospitals in the pandemic of SARS-CoV-2. Two hundred fifth-eight PD patients answered the questionnaire. There were various opinions about anxiety such as "PD patients are susceptible and vulnerable to SARS-CoV-2" (36.8%). Concerning the troubles in the pandemic, the most frequent answer was that they couldn't participate in the rehabilitation and elderly day care (38.4%). Relatively many PD patients requested telemedicine (29.5%), whereas some people hoped face-to-face medical care (8.1%). There were demands about the delivery of medications (50.0%), the establishment of telephone consultations (43.8%), resources for rehabilitation at home (43.8%). The medical care adapted to the anxiety, trouble and requests of PD patients will be required in the era when we have to live with SARS-CoV-2.

Visible light activation of photocatalysts formed from the heterojunction of sludge-generated TiO2 and g-CN towards NO removal.

The feasibility of preparing TiO2/g-CN heterojunction from Ti-incorporated dried dye wastewater sludge is explored in this study. Two reaction routes of composite formation were evaluated. In the initial approach, one-step calcination of dried sludge and melamine mixture @600 °C was carried out. Detailed morphological and chemical characterizations showed that the one-step calcination route did not create TiO2/g-CN composites; instead, only N-doped anatase TiO2 composites were formed. Moreover, due to the non-uniform composition of organic content in the dried sludge, it was not easy to control the N doping level by varying melamine content (0-100%) in the precursor mix. However, successful formation of anatase TiO2 and g-CN was observed when a two-step calcination route was followed, i.e., via synthesis of anatase TiO2 from dried sludge, and later development of heterojunction by calcining (@550 °C) the TiO2 and melamine mixture. X-ray diffraction along with infrared and X-ray photoelectron spectroscopy verified the effective heterojunction. In addition, maximum atmospheric NO removal under UV and visible light were observed for the prepared composite when the melamine content in the precursor mixture was 70%. After 1 h of UV and visible light irradiation, the best TiO2/g-CN composite removed 25.71% and 13.50% of NO, respectively. Optical characterization suggested that the enhanced NO oxidation under UV/visible light was due to the bandgap narrowing and diminished photogenerated electron-hole recombination.

Complete decomposition of sulfamethoxazole during an advanced oxidation process in a simple water treatment system.

A simple water treatment system consisting of a deep UV light (λ = 222 nm) source, a mesoporous TiO2/boron-doped diamond (BDD) photocatalyst, and a BDD electrode was prepared and used to decompose sulfamethoxazole (SMX) in an advanced oxidation process. The mesoporous TiO2/BDD photocatalyst used with the electrochemical treatment promoted SMX decomposition, but the mesoporous TiO2/BDD photocatalyst alone had a similar ability to decompose SMX as photolysis. Fragments produced through photocatalytic treatment were decomposed during the electrochemical treatment and fragments produced during the electrochemical treatment were decomposed during the photocatalytic treatment, so performing the electrochemical and photocatalytic treatments together effectively decomposed SMX and decrease the total organic carbon concentration to a trace.

Rod-Shaped ß-FeOOH Synthesis for Hydrogen Production under Light Irradiation.

Renewable energy is spotlighted as a resource to replace fossil fuels, and among the resources, active research on hydrogen energy is ongoing. Various methods have been developed to produce hydrogen energy using photoreduction processes. In this study, we synthesized ß-phase iron oxyhydroxide (ß-FeOOH) using a hydrothermal method with an optimal synthesis time and investigated its photofunctional properties, including hydrogen production. The obtained samples were characterized and compared with reference data. X-ray powder diffraction results corresponded to the peaks of the reference data. A rod structure was confirmed by scanning electron microscopy, and no impurities were observed. The band-gap energy of ß-FeOOH was calculated as 1.8-2.6 eV. A photoreduction process was performed based on a photo-Fenton reaction to produce hydrogen by irradiating ultraviolet (UV) on ß-FeOOH. The synthesized ß-FeOOH was subjected to UV irradiation for 24 h to produce hydrogen, and we confirmed that hydrogen was successfully produced. The properties of ß-FeOOH were evaluated after UV irradiation.

Long-Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open-Label Study.

INTRODUCTION: Early discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted. OBJECTIVE: This study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients. METHODS: In this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores. RESULTS: A total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months. CONCLUSIONS: Fremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03303105.

Functional Depletion of HSP72 by siRNA and Quercetin Enhances Vorinostat-Induced Apoptosis in an HSP72-Overexpressing Cutaneous T-Cell Lymphoma Cell Line, Hut78.

Histone deacetylase inhibitors (HDACis) are one of the therapeutic options for cutaneous T-cell lymphoma (CTCL), but they have limited effects. We previously demonstrated that HSP72 overexpression is associated with chemoresistance to HDACis in lymphoma cells. The purpose of this study was to investigate whether the functional depletion of HSP72 enhances the effect of the HDACi vorinostat. First, we established a stable HSP72-knockdown CTCL cell line and confirmed the influence of HSP72 reduction on the antitumor effects of vorinostat. Next, we studied the effect of quercetin, an inhibitor of HSP72, on the antineoplastic effects of vorinostat. In five CTCL cell lines examined, HSP72 expression was highest in Hut78 cells, and HSP72 knockdown enhanced vorinostat-induced apoptosis in these cells. Low-dose quercetin reduced HSP72 expression, increased HDAC activity, and enhanced vorinostat-induced suppression of Hut78 cell proliferation. A single low dose of quercetin induced G2 arrest and only slightly increased the sub-G1 cell fraction. Quercetin also significantly enhanced vorinostat-induced apoptosis, caspase-3, caspase-8, and caspase-9 activity, and the loss of mitochondrial membrane potential. HSP72 knockdown enhanced vorinostat-induced apoptosis in an HSP72-overexpressing CTCL cell line, and thus, quercetin may be a suitable candidate for combination therapy with vorinostat in clinical settings.