Long-term neuropeptide modulation of female sexual drive via the TRP channel in Drosophila melanogaster.

Connectomics research has made it more feasible to explore how neural circuits can generate multiple outputs. Female sexual drive provides a good model for understanding reversible, long-term functional changes in motivational circuits. After emerging, female flies avoid male courtship, but they become sexually receptive over 2 d. Mating causes females to reject further mating for several days. Here, we report that pC1 neurons, which process male courtship and regulate copulation behavior, exhibit increased CREB (cAMP response element binding protein) activity during sexual maturation and decreased CREB activity after mating. This increased CREB activity requires the neuropeptide Dh44 (Diuretic hormone 44) and its receptors. A subset of the pC1 neurons secretes Dh44, which stimulates CREB activity and increases expression of the TRP channel Pyrexia (Pyx) in more pC1 neurons. This, in turn, increases pC1 excitability and sexual drive. Mating suppresses pyx expression and pC1 excitability. Dh44 is orthologous to the conserved corticotrophin-releasing hormone family, suggesting similar roles in other species.

Minimizing the Carrier Collection Loss of the Neutral-Color Transparent Crystalline-silicon Solar Modules via Hybrid Electrode Design.

Transparent solar cells can be used where conventional solar cells are inapplicable, such as, in glass windows of buildings; however, reports on modularization, which is essential for their commercialization, are scarce. Here, a novel modularization method has been proposed for the fabrication of transparent solar cells and a 100-cm2 neutral-color transparent crystalline-silicon solar module has been developed using a hybrid electrode comprising a microgrid electrode and an edge busbar electrode. The transparent solar module exhibits a power conversion efficiency (PCE) of 11.94 and 13.14% when connected in series and in parallel, respectively, with an average visible transmittance of 20%. Additionally, the module exhibits negligible losses in PCE (lower than 0.23%) in outdoor, mechanical-load, and damp-heat (at 85°C/85% RH) stability tests, indicating high stability. The transparent solar module proposes here could facilitate the commercialization of transparent solar cells.

The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer's Disease Mouse Model.

Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer's disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer's disease treatment and that natural alkaloids are potential sources of mitophagy inducers.

Berberine Induces Mitophagy through Adenosine Monophosphate-Activated Protein Kinase and Ameliorates Mitochondrial Dysfunction in PINK1 Knockout Mouse Embryonic Fibroblasts.

Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not interfere with mitochondrial function, unlike the well-known mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and subsequently induced mitochondrial biogenesis. Berberine treatment induced the activation of adenosine monophosphate-activated protein kinase (AMPK), and the AMPK inhibitor compound C abolished berberine-induced mitophagy, suggesting that AMPK activation is essential for berberine-induced mitophagy. Notably, berberine treatment reversed mitochondrial dysfunction in PINK1 knockout mouse embryonic fibroblasts. Our results suggest that berberine is a mitophagy-specific inducer and can be used as a therapeutic treatment for neurodegenerative diseases, including Parkinson's disease, and that natural alkaloids are potential sources of mitophagy inducers.

Is It Really Safe to Discontinue Anticoagulant Treatment Before Ptosis Surgery From Serious Bleeding?

PURPOSE: To evaluate the effects of discontinuing anticoagulants (ACs)/antiplatelets (APs) preoperatively on surgery for blepharoptosis. METHOD: A retrospective analysis included patients with acquired blepharoptosis who underwent surgical correction, and were followed for more than 1 month. Patients were classified into 2 groups depending on AC/AP treatment or otherwise. All patients taking AC/AP discontinued with the treatment 1 week prior to surgery in accordance with our clinical guidelines. Preoperative and postoperative marginal reflex distance 1 (MRD1) and ecchymosis grade were evaluated and compared. RESULTS: Group 1 (AC/AP treatment cessation) included 47 patients with 93 eyelids, and group 2 (control) included 51 patients with 98 eyelids. The preoperative MRD1 showed no significant difference between groups. Group 1 showed a significantly higher rate of severe ecchymosis (41.8 versus 22.4%, P = 0.004) at 1 week of surgery as well as persistent ecchymosis (58.8 versus 7.3%, P = 0.000) compared with group 2 postoperatively at 1 month. Postoperative MRD1 was significantly lower in group 1 at 1 week (P = 0.019). However, the MRD1 and degree of improvement in lid height (postoperative MRD1 "preoperative MRD1) was not significantly different between the 2 groups (P = 0.499, P = 0.058) at 1 month postoperatively. CONCLUSIONS: Postoperative ecchymosis was more severe in group 1 at 1 month after ptosis surgery even though the ACs/APs were discontinued. Surgeons should be careful about this before operation. THE SYNOPSIS: Significant ecchymosis could occur even after discontinuation of antithrombotic agents in patients with a history of taking medication in ptosis surgery. Surgeons should be careful about this before operation.

Sunlight-Activatable ROS Generator for Cell Death Using TiO2/c-Si Microwires.

Solar-driven reactive oxygen species (ROS) generation is an attractive disinfection technique for cell death and water purification. However, most photocatalysts require high stability in the water environment and the production of ROS with a sufficient amount and diffusion length to damage pathogens. Here, a ROS generation system was developed consisting of tapered crystalline silicon microwires coated with anatase titanium dioxide for a conformal junction. The system effectively absorbed >95% of sunlight over 300-1100 nm, resulting in effective ROS generation. The system was designed to produce various ROS species, but a logistic regression analysis with cellular survival data revealed that the diffusion length of the ROS is ∼9 µm, implying that the most dominant species causing cell damage is H2O2. Surprisingly, a quantitative analysis showed that only 15 min of light irradiation on the system would catalyze a local bactericidal effect comparable to the conventional germicidal level of H2O2 (∼3 mM).

Transient midventricular ballooning syndrome with thrombus post pericardiocentesis in a patient with malignant breast cancer.

One day after pericardiocentesis for pericardial effusion in a patient with malignant breast cancer, the clinical and echocardiographic examination for recurrent dyspnea suggested stress cardiomyopathy with mid left ventricular ballooning and thrombus rather than pericardial decompression syndrome. Physicians should therefore pay attention to the possibility of ventricular dysfunction with thrombus post pericardiocentesis and to differences between stress cardiomyopathy and pericardial decompression syndrome. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:53-57, 2017.

Dopant-Free All-Back-Contact Si Nanohole Solar Cells Using MoOx and LiF Films.

We demonstrate novel all-back-contact Si nanohole solar cells via the simple direct deposition of molybdenum oxide (MoOx) and lithium fluoride (LiF) thin films as dopant-free and selective carrier contacts (SCCs). This approach is in contrast to conventionally used high-temperature thermal doping processes, which require multistep patterning processes to produce diffusion masks. Both MoOx and LiF thin films are inserted between the Si absorber and Al electrodes interdigitatedly at the rear cell surfaces, facilitating effective carrier collection at the MoOx/Si interface and suppressed recombination at the Si and LiF/Al electrode interface. With optimized MoOx and LiF film thickness as well as the all-back-contact design, our 1 cm(2) Si nanohole solar cells exhibit a power conversion efficiency of up to 15.4%, with an open-circuit voltage of 561 mV and a fill factor of 74.6%. In particular, because of the significant reduction in Auger/surface recombination as well as the excellent Si-nanohole light absorption, our solar cells exhibit an external quantum efficiency of 83.4% for short-wavelength light (∼400 nm), resulting in a dramatic improvement (54.6%) in the short-circuit current density (36.8 mA/cm(2)) compared to that of a planar cell (23.8 mA/cm(2)). Hence, our all-back-contact design using MoOx and LiF films formed by a simple deposition process presents a unique opportunity to develop highly efficient and low-cost nanostructured Si solar cells.

Methyl Red Decolorization Efficiency of a Korea Strain of Aspergillus sp. Immobilized into Different Polymeric Matrices.

Intensive research studies have revealed that fungal decolorization of dye wastewater is a promising replacement for the current process of dye wastewater decolorization. The authors isolated an Aspergillus sp. from the effluent of a textile industry area in Korea and assessed the effects of a variety of operational parameters on the decolorization of methyl red (MR) by this strain of Aspergillus sp. This Aspergillus sp. was then immobilized by entrapment in several polymeric matrices and the effects of operational conditions on MR decolorization were investigated again. The optimal decolorization activity of this Aspergillus sp. was observed in 1% glucose at a temperature of 37 °C and pH of 6.0. Furthermore, stable decolorization efficiency was observed when fungal biomass was immobilized into alginate gel during repeated batch experiment. These results suggest that the Aspergillus sp. isolated in Korea could be used to treat industrial wastewaters containing MR dye.

Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy.

Background: To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). Methods: This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. Results: In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups. Conclusion: OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.

Mitophagy induction upon mitochondrial stress is critical for maintaining mitochondrial homeostasis and cellular function. Here, we found that Mst1/2 (Stk3/4), key regulators of the Hippo pathway, are required for the induction of mitophagy under various mitochondrial stress conditions. Knockdown of Mst1/2 or pharmacological inhibition by XMU-MP-1 treatment led to impaired mitophagy induction upon CCCP and DFP treatment. Mechanistically, Mst1/2 induces mitophagy independently of the PINK1-Parkin pathway and the canonical Hippo pathway. Moreover, our results suggest the essential involvement of BNIP3 in Mst1/2-mediated mitophagy induction upon mitochondrial stress. Notably, Mst1/2 knockdown diminishes mitophagy induction, exacerbates mitochondrial dysfunction, and reduces cellular survival upon neurotoxic stress in both SH-SY5Y cells and Drosophila models. Conversely, Mst1 and Mst2 expression enhances mitophagy induction and cell survival. In addition, AAV-mediated Mst1 expression reduced the loss of TH-positive neurons, ameliorated behavioral deficits, and improved mitochondrial function in an MPTP-induced Parkinson's disease mouse model. Our findings reveal the Mst1/2-BNIP3 regulatory axis as a novel mediator of mitophagy induction under conditions of mitochondrial stress and suggest that Mst1/2 play a pivotal role in maintaining mitochondrial function and neuronal viability in response to neurotoxic treatment.

A novel marine-derived mitophagy inducer ameliorates mitochondrial dysfunction and thermal hypersensitivity in paclitaxel-induced peripheral neuropathy.

BACKGROUND AND PURPOSE: Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model. EXPERIMENTAL APPROACH: Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae. KEY RESULTS: PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction. CONCLUSION AND IMPLICATIONS: This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds.

Atypical meningiomas: is postoperative radiotherapy indicated?

OBJECT: The role of postoperative radiation therapy after surgery for atypical meningiomas remains controversial. In this retrospective cohort study, the authors examine the recurrence rates for atypical meningiomas after resection (with or without adjuvant radiotherapy) and identify which factors were associated with recurrence. METHODS: Of 90 patients with atypical meningiomas who underwent surgery between 1999 and 2009, 71 (79%) underwent gross-total resection (GTR) and 19 (21%) underwent subtotal resection (STR); 31 patients received adjuvant radiotherapy. All tumors were pathology-confirmed WHO Grade II atypical meningiomas. Univariate and multivariate analyses were performed to identify factors associated with recurrence-free survival. RESULTS: Among 90 patients, 17 developed tumor recurrence (81% recurrence-free survival at 5 years). In the overall group, adjuvant radiotherapy reduced the recurrence rate to 9% from 19% at 5 years (p = 0.048). After STR, adjuvant radiotherapy significantly reduced recurrence from 91% to 20% (p = 0.0016). However, after GTR, adjuvant radiotherapy did not significantly reduce the recurrence rate (16.7% without radiation therapy vs 11.8% with radiation therapy) (p = 1.00). Five factors independently predictive of tumor recurrence included mitotic index, sheeting, necrosis, nonuse of radiation therapy, and STR. Further recursive partitioning analysis showed significant increases in risk for patients older than 55 years with mitoses and sheeting. CONCLUSIONS: Adjuvant radiotherapy was effective at lowering recurrence rates in patients after STR but delivered no significant improvement in patients after GTR. Given that rates after GTR were similar with or without adjuvant radiotherapy, close observation without postoperative radiation therapy may be a viable option for these patients. Patients older than 55 years and those with mitoses noted during pathological examination had a significant risk of recurrence after GTR; for these patients, postoperative radiotherapy is recommended.

Proinflammatory cytokine IL-1 ß polymorphisms in sudden sensorineural hearing loss.

The cause and pathogenesis of sudden sensorineural hearing loss (SSNHL) remain unknown. IL-1ß is one of the most powerful inflammatory cytokines. The aim of this study was to evaluate the relationships between interleukin-1 ß (IL-1ß) gene polymorphisms (-511 C/T and +3953 C/T) in patients with SSNHL. One hundred two patients affected by SSNHL and 595 controls were genotyped for IL-1ß gene polymorphisms. The polymorphisms were analyzed by polymerase chain reaction amplification and DNA fragment separation via electrophoresis. Compared to controls, the IL-1ß (+3953) T allele increased the relative risk of SSNHL in subjects with IL-1ß (-511) TT genotype (p = 0.022, OR = 9.111, 95% CI = 1.441-57.618). In this study, polymorphisms in the IL-1ß -511 and IL-1ß +3953 loci were assessed for evidence of association with SSNHL. From this assessment, a significant difference in carriage of both the IL-1ß -511 T allele and the IL-1ß +3953 T allele was observed between SSNHL and controls. This suggests that the IL-1ß -511 and +3953 loci may play an important role in the etiopathogenesis of SSNHL.

Intraoperative use of fibrin glue in blepharoplasty: a possible solution to reduce postoperative complication.

The purpose of this study was to investigate the effects of intraoperative fibrin glue use on surgery for blepharoptosis. This retrospective study included patients with acquired blepharoptosis who underwent surgical correction and were followed for at least one month. Patients were classified into two groups depending on whether treated with antithrombotic agents or otherwise. All patients taking antithrombotic agents discontinued with the treatment one week prior to surgery in accordance with our clinical guidelines. Preoperative and postoperative marginal reflex distance 1(MRD1) and ecchymosis grade were evaluated and compared. The subjects were 56 patients (111 eyes) who discontinued antithrombotic agents before surgery and 59 patients (117 eyes) who had never taken antithrombotic agents. Fibrin glue was used in 13 patients (26 eyes, 23.4%) in the antithrombotic group, and 11 patients (21 eyes, 17.9%) in the non-antithrombotic group. The rate of severe ecchymosis was significantly lower in patients who used fibrin glue in the antithrombotic group at 1 week (11.5 vs 40.0%, p = 0.008). However, in non-antithrombotic group, there was no difference in the rate of severe ecchymosis according to the use of fibrin glue at 1 week (14.3 vs 30.2%, p = 0.181). In patients with a history of taking antithrombotic agents, the intraoperative use of fibrin glue is thought to be helpful as it could significantly reduce significant ecchymosis.

Effect of Magnetic Microparticles on Cultivated Human Corneal Endothelial Cells.

Purpose: To investigate effects of magnetic microparticles on movement of magnet controlled human corneal endothelial cells (HCECs). Methods: Immortalized HCEC line (B4G12) and primary culture of HCECs were exposed to two commercially available magnetic micro- or nanoparticles, SiMAG (average size 100 nm) and fluidMAG (average size <1000 nm). Cell viability assays and reactive oxygen species production assays were performed. Cellular structural changes, intracellular distribution of microparticles, and expression levels of proteins related to cellular survival were analyzed. Ex vivo human corneas were exposed to microparticles to further evaluate their effects. Magnetic particle-laden HCECs were cultured under the influence of a neodymium magnet. Results: No significant decrease of viability was found in HCECs after exposure to both magnetic particles at concentrations up to 20 µg/mL for 48 hours. However, high concentrations (40 µg/mL and 80 µg/mL) of SiMAG and FluidMAG significantly decreased viability in immortalized HCECs, and only 80 µg/mL of SiMAG and FluidMAG decreased viability in primary HCECs after 48 hours of exposure. There was relative stability of viability at various concentrations of magnetic particles, despite a dose-dependent increase of reactive oxygen species, lactate dehydrogenase, and markers of apoptosis. Ex vivo human cornea study further revealed that exposure to 20 µg/mL of SiMAG and fluidMAG for 72 hours was tolerable. Endocytosed magnetic particles were mainly localized in the cytoplasm. The application of a magnetic field during cell culture successfully demonstrated that magnetic particle-loaded HCECs moved toward the magnet area and that the population density of HCECs was significantly increased. Conclusions: We verified short-term effects of SiMAG and fluidMAG on HCECs and their ability to control movement of HCECs by an external magnetic field. Translational Relevance: A technology of applying magnetic particles to a human corneal endothelial cell culture and controlling the movement of cells to a desired area using a magnetic field could be used to increase cell density during cell culture or improve the localization of corneal endothelial cells injected into the anterior chamber to the back of the cornea.

Dry Eye Assessment of Patients Undergoing Endoscopic Dacryocystorhinostomy for Nasolacrimal Duct Obstruction Combined with Dry Eye Syndrome.

PURPOSE: To evaluate the prevalence of dry eye symptoms after endoscopic dacryocystorhinostomy (EDCR) for patients with primary acquired nasolacrimal duct obstruction (PANDO) combined with dry eye syndrome. METHODS: The patients diagnosed with PANDO combined with dry eye syndrome who underwent EDCR were divided into two groups according to the questionnaire about dry eye symptoms after surgery. The medical records were retrospectively analyzed. Before and after surgery, we compared the tear meniscus height, tear breakup time, and the presence of corneal punctuate epithelial erosion. The level of dry eyes of patients after surgery was assessed by using the Korean guidelines for the diagnosis of dry eye. RESULTS: At 6 months after EDCR, the proportion of patients with dry eye symptoms was 30% in a total of 80 patients. The duration of epiphora and tear breakup time after EDCR were higher in the group without dry eye symptoms and the proportion of eyes with corneal punctuate epithelial erosion after EDCR was higher in the group with dry eye symptoms. About 15% of total patients started treatment with a dry eye of level 2 or higher. CONCLUSIONS: About 15% of patients who underwent EDCR for PANDO combined with dry eye syndrome developed significant dry eye syndrome after surgery. The short onset of epiphora was associated with the development of the dry eye symptoms. Therefore, it is necessary to evaluate dry eye syndrome before surgery, and surgeons should be careful about this.

Advances in ophthalmic drug delivery technology for postoperative management after cataract surgery.

INTRODUCTION: Cataract surgery is becoming more common due to an aging world population. Intraocular lenses and surgical technique have developed remarkably recently, but the development of postoperative medication to prevent postsurgery complications has been relatively delayed. We still largely depend on eye drops for the management of post-cataract-surgery patients. Mental and physical problems that often occur in elderly cataract patients make it difficult for patients to apply eye drops by themselves. It is necessary to develop new effective drug delivery methods. AREAS COVERED: This updated review article provides a brief review of why drug management is needed following cataract surgery and an overview of current developments in new drug delivery methods for ophthalmic treatment. In particular, various novel drug delivery methods that can be used for post-cataract-surgery management and their current development stages are extensively reviewed. EXPERT OPINION: Rapidly developing technologies, such as intraocular and external ophthalmic implants, polymers, and nanotechnology, are being actively applied to develop novel drug delivery systems for safe and effective management after cataract surgery. Their goal is to achieve sufficient drug release for the desired duration with a single application. These will largely replace the inconvenience of eye drops for elderly patients in the future.

The PINK1 Activator Niclosamide Mitigates Mitochondrial Dysfunction and Thermal Hypersensitivity in a Paclitaxel-Induced Drosophila Model of Peripheral Neuropathy.

Paclitaxel is a widely used anticancer drug that induces dose-limiting peripheral neuropathy. Mitochondrial dysfunction has been implicated in paclitaxel-induced neuronal damage and in the onset of peripheral neuropathy. We have previously shown that the expression of PINK1, a key mediator of mitochondrial quality control, ameliorated the paclitaxel-induced thermal hyperalgesia phenotype and restored mitochondrial homeostasis in Drosophila larvae. In this study, we show that the small-molecule PINK1 activator niclosamide exhibits therapeutic potential for paclitaxel-induced peripheral neuropathy. Specifically, niclosamide cotreatment significantly ameliorated the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae in a PINK1-dependent manner. Paclitaxel-induced alteration of the dendrite structure of class IV dendritic arborization (C4da) neurons was not reduced upon niclosamide treatment. In contrast, paclitaxel treatment-induced increases in both mitochondrial ROS and aberrant mitophagy levels in C4da neurons were significantly suppressed by niclosamide. In addition, niclosamide suppressed paclitaxel-induced mitochondrial dysfunction in human SH-SY5Y cells in a PINK1-dependent manner. These results suggest that niclosamide alleviates thermal hyperalgesia by attenuating paclitaxel-induced mitochondrial dysfunction. Taken together, our results suggest that niclosamide is a potential candidate for the treatment of paclitaxel-induced peripheral neuropathy with low toxicity in neurons and that targeting mitochondrial dysfunction is a promising strategy for the treatment of chemotherapy-induced peripheral neuropathy.

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status.

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors' knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images.