Mehanizam akutne neurotoksičnosti u Sprague-Dawley štakora izazvane trovanjem endosulfanom

The purpose of this study was to investigate the molecular mechanism underlying oxidative and inflammatory neuronal cell death induced by endosulfan, a pesticide belonging to the chemical family of organochlorines. The cortical and hippocampal tissues derived from Sprague-Dawley (SD) rats treated with endosulfan exhibited increased intracellular accumulation of reactive oxygen species and oxidative damages to cellular macromolecules such as depletion of glutathione, lipid peroxidation, and protein carbonylation. Conversely, the expression of antioxidant enzymes including γ-glutamylcysteine ligase (GCL), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) was markedly reduced in the brain tissues exposed to endosulfan. Moreover, during endosulfan-induced neuronal cell death, mRNA expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was elevated, which seemed to be mediated by the activation of nuclear factor-kappa B (NF-κB) by phosphorylation of p65 subunit. These results suggest a new molecular mechanism underlying the endosulfan-induced acute neurotoxicity via induction of oxidative stress and pro-inflammatory responses.Istražen je molekularni mehanizam koji dovodi do smrti neurona potaknute oksidativnim i upalnim procesima uzrokovanim organoklornim pesticidom endosulfanom. U tkivima korteksa i hipokampusa Sprague-Dawley (SD) štakora tretiranih endosulfanom uočena su oksidativna oštećenja staničnih makromolekula, poput smanjene razine glutationa, lipidne peroksidacije i karbonilacije proteina, te povećane unutarstanične akumulacije reaktivnih kisikovih spojeva. Isto tako, u moždanom tkivu nakon izlaganja endosulfanu značajno je smanjena ekspresija enzimskih antioksidansa, uključujući i γ-glutamilcistein ligazu (GCL), superoksidnu dismutazu (SOD) i hem oksigenazu-1 (HO-1). Tijekom endosulfanom izazvane smrti neurona povećala se i ekspresija mRNA pro-upalnih citokina poput čimbenika nekroze tumora-α (TNF-α) i interleukina-1β (IL-1β), što je čini se bilo posredovano aktivacijom nuklearnoga faktora kapa B (NF-κB) putem fosforilacije podjedinice p65. Navedeni rezultati upućuju na novi molekularni mehanizam koji stoji iza akutne neurotoksičnosti izazvane endosulfanom putem indukcije oksidativnoga stresa i pro-upalnih odgovora

Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN

Enhancing photoluminescence quantum efficiency of metal halide perovskites by examining luminescence-limiting factors

Metal halide perovskites (MHPs) show superior optoelectronic properties, which give them the great potential for use in next generation light-emitting diodes (LEDs). In particular, their narrow emission linewidths can achieve ultrahigh color purity. However, the reported luminescence efficiency (LE) values are not high enough to be commercialized in displays and solid-state lightings. Moreover, the operational stability of LEDs associated with the overshooting of luminance and the high relative standard deviation of reported external quantum efficiencies are still problematic. In this perspective, we review photophysical factors that limit the photoluminescence quantum efficiency of perovskite-based LEDs. These factors are categorized into (i) weak exciton binding, (ii) nonradiative recombinations, (iii) slow cooling of long-lived hot carriers, (iv) deep-level defects, and (v) interband transition rates. We then present various physicochemical methods to effectively overcome these luminescence-limiting factors. We finally suggest some useful research directions to further improve the LE of MHP emitters as core components in displays and solid-state lightings.

Imaging findings of mimickers of hepatocellular carcinoma

Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC) as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis

The Risk of Type 2 Diabetes Mellitus according to Changes in Obesity Status in Late Middle-Aged Adults: A Nationwide Cohort Study of Korea

Background Although obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), there is scant data on discriminating the contribution of previous obesity and recent weight gain on developing T2DM. Methods We analyzed the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 where Korean residents underwent biennial health checkups. Participants were classified into four groups according to their obesity status (body mass index [BMI] ≥25 kg/m2) before and after turning 50 years old: maintaining normal (MN), becoming obese (BO), becoming normal (BN), and maintaining obese (MO). Cox proportional hazards regression model was used to estimate the risk of T2DM factoring in the covariates age, sex, BMI, presence of impaired fasting glucose or hypertension, family history of diabetes, and smoking status. Results A total of 118,438 participants (mean age, 52.5±1.1 years; men, 45.2%) were prospectively evaluated for incident T2DM. A total of 7,339 (6.2%) participants were diagnosed with T2DM during a follow-up period of 4.8±2.6 years. Incidence rates of T2DM per 1,000 person-year were 9.20 in MN, 14.81 in BO, 14.42 in BN, 21.38 in MO. After factoring in covariates, participants in the groups BN (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04 to 1.27) and MO (aHR, 1.14; 95% CI, 1.06 to 1.24) were at increased risk of developing T2DM compared to MN, whereas BO (hazard ratio, 1.06; 95% CI, 0.96 to 1.17) was not. Conclusion Having been obese before 50 years old increased the risk of developing T2DM in the future, but becoming obese after 50 did not. Therefore, it is important to maintain normal weight from early adulthood to prevent future metabolic perturbations

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

Objectives Antiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS). Methods Thirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 μL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue. Results AOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1β in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group. Conclusion In spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation

Decreased Expression of 15-hydroxyprostaglandin Dehydrogenase in Gastric Carcinomas

prostaglandin E2 (PGE2) when compared to non-neoplastic mucosa, and cyclooxygenase-2 (COX-2), which is the ratelimiting enzyme in prostaglandin (PG) biosynthesis, is often overexpressed in gastric carcinomas and during gastric carcinogenesis. However, little is known about the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for the biological inactivation of PG, in gastric carcinomas. Materials and Methods: We investigated the expression of 15-PGDH in 28 cases of advanced gastric carcinomas by Western blot analysis and also the relation between its expression and the gene promoter methylation. Results: 15-PGDH expression was significantly decreased in gastric carcinomas compared to corresponding non-neoplastic tissues and inversely correlated with the expression of proliferating cell nuclear antigen in gastric carcinomas. However, there was no correlation between 15-PGDH expression and pathological findings such as nodal metastasis and vascular invasion. Promoter hypermethylation of 15-PGDH gene was not detected in carcinomas, with only a negligible expression of the enzyme. Conclusion: Our results suggested that 15-PGDH has tumor suppressor activity in gastric carcinomas. Key Words: 15-hydroxyprostaglandin dehydrogenase, gastric carcinoma, methylatio

Leptomeningeal Dissemination of a Low-Grade Brainstem Glioma without Local Recurrence

It is rare for low-grade gliomas to disseminate to the leptomeninges. However, low-grade gliomas with dissemination to the leptomeninges have been occasionally reported in children, and have generally been associated with local recurrence. A 16-year-old boy sought evaluation for diplopia and gait disturbance. A brain magnetic resonance imaging (MRI) revealed pontine mass, which was proved to be fibrillary astrocytoma on biopsy, later. Radiation therapy (5400 cGy) was given and the patient's symptoms were improved. He was followed-up radiologically for brain lesion. Seven months after diagnosis he complained of back pain and gait disturbance. A brain MRI showed a newly-developed lesion at the left cerebellopontine angle without an interval change in the primary lesion. A spinal MRI demonstrated leptomeningeal dissemination of the entire spine. Radiation therapy (3750 cGy) to the spine, and adjuvant chemotherapy with a carboplatin plus vincristine regimen were administered. However, he had a progressive course with tumoral hemorrhage and expired 13 months after diagnosis. We report an unusual case of a low-grade brainstem glioma with spinal dissemination, but without local recurrence, and a progressive course associated with hemorrhage

Enhancing exciton diffusion in monolayer WS2 with h-BN bottom layer

We investigated two-dimensional (2D) exciton diffusion in monolayer WS2 on both SiO2 and hexagonal boron nitride (h-BN) layers to identify the exciton diffusion enhanced by the h-BN bottom layer using spatially resolved photoluminescence imaging combined with time-resolved spectroscopy. The WS2 on the h-BN bottom layer shows an exciton diffusion coefficient of 38cm2/s, which is almost 1.7 times that of WS2 on the SiO2 layer. Electrostatic force microscopy confirms that the increase in the 2D exciton diffusion is mainly due to the reduction in the charge impurities and traps on the h-BN surface compared to the SiO2 surface. © 2019 American Physical Society.1

Treatment of Two Level Artificial Disc Replacement for Cervical Spondylotic Myelopathy

Cervical spondylotic myelopathy (CSM) is a common spinal disorder caused by compression of the spinal cord, due to degeneration of the cervical spine. We investigated post-operative results and suggest artificial disc replacement (ADR) as an effective surgical method for treating CSM. We present the case of a 36-year-old man, with nuchal pain; severe paresthesia of both upper and lower extremities; and pain, motor weakness, and difficulty in fine motor control of both hands. A cervical X-ray showed spondylotic changes at the C5-6, C6-7 level and MRI revealed cord compression at the C5-6, C6-7 level. ADR was performed at the C5-6, C6-7 level. After the surgery, the motor weakness of both upper extremities and paresthesia of both aspects improved. In addition, the JOA score and Nurick grade improved. A post-operative X-ray showed well positioned instruments, and post- operative MRI displayed no lesions of cord compression. Anterior cervical discectomy and fusion (ACDF) is widely accepted as a leading treatment for CSM, but ACDF may cause adjacent segment disease (ASD). We suggest that ADR also can represent a good surgical procedure for the management of multilevel spinal cord compression, as it can preserve cervical motion while avoiding AS