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Rationale: Renal artery pseudoaneurysm is a rare vascular lesion usually caused by trauma or percutaneous urological procedures. Spontaneous rupture of pseudoaneurysms without predisposing events, especially in hemodialysis patients, has rarely been reported., Patient Concerns: A 25-year-old man receiving maintenance hemodialysis visited the emergency room because of sudden severe right flank pain. He had no history of trauma or urological procedures except for a left renal biopsy to diagnose Alport syndrome 10 years prior., Diagnosis: Contrast-enhanced computed tomography revealed a right perirenal hematoma with pseudoaneurysms., Interventions: On renal angiography, multiple pseudoaneurysms were observed in the right renal artery branches and embolization was performed., Outcomes: Post-angiography showed no pseudoaneurysms. His abdominal pain improved, and he was discharged 2 weeks after embolization., Lessons: When maintenance dialysis patients complain of severe abdominal pain, spontaneous rupture of a renal pseudoaneurysm should be considered as a differential diagnosis, even if the patient has no history of trauma or previous urological procedures., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment ( N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19., Competing Interests: Competing interest statement: K.G.V. is a part-owner of VAL Health, a behavioral economics consulting firm., (Copyright © 2021 the Author(s). Published by PNAS.)

Soluble guanylate cyclase (sGC) is a clinically validated therapeutic target in the treatment of pulmonary hypertension. Modulators of sGC have the potential to treat diseases that are affected by dysregulation of the NO-sGC-cGMP signal transduction pathway. This letter describes the SAR efforts that led to the discovery of CYR715, a novel carboxylic acid-containing sGC stimulator, with an improved metabolic profile relative to our previously described stimulator, IWP-051. CYR715 addressed potential idiosyncratic drug toxicity (IDT) liabilities associated with the formation of reactive, migrating acyl glucuronides (AG) found in related carboxylic acid-containing analogs and demonstrated high oral bioavailability in rat and dose-dependent hemodynamic pharmacology in normotensive Sprague-Dawley rats., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To test the hypothesis that glutamate and GABA are linked to the formation of epilepsy networks and the triggering of spontaneous seizures, we examined seizure initiation/propagation characteristics and neurotransmitter levels during epileptogenesis in a translationally relevant rodent model of mesial temporal lobe epilepsy., Methods: The glutamine synthetase (GS) inhibitor methionine sulfoximine was infused into one of the hippocampi in laboratory rats to create a seizure focus. Long-term video-intracranial EEG recordings and brain microdialysis combined with mass spectrometry were used to examine seizure initiation, seizure propagation, and extracellular brain levels of glutamate and GABA., Results: All seizures (n = 78 seizures, n = 3 rats) appeared first in the GS-inhibited hippocampus of all animals, followed by propagation to the contralateral hippocampus. Propagation time decreased significantly from 11.65 seconds early in epileptogenesis (weeks 1-2) to 6.82 seconds late in epileptogenesis (weeks 3-4, paired t test, p = 0.025). Baseline extracellular glutamate levels were 11.6-fold higher in the hippocampus of seizure propagation (7.3 µM) vs the hippocampus of seizure onset (0.63 µM, analysis of variance/Fisher least significant difference, p = 0.01), even though the concentrations of the major glutamate transporter proteins excitatory amino acid transporter subtypes 1 and 2 and xCT were unchanged between the brain regions. Finally, extracellular GABA in the seizure focus decreased significantly from baseline several hours before a spontaneous seizure (paired t test/false discovery rate)., Conclusion: The changes in glutamate and GABA suggest novel and potentially important roles of the amino acids in epilepsy network formation and in the initiation and propagation of spontaneous seizures., (© 2021 American Academy of Neurology.)

The enzyme glutamine synthetase (GS), also referred to as glutamate ammonia ligase, is abundant in astrocytes and catalyzes the conversion of ammonia and glutamate to glutamine. Deficiency or dysfunction of astrocytic GS in discrete brain regions have been associated with several types of epilepsy, including medically-intractable mesial temporal lobe epilepsy (MTLE), neocortical epilepsies, and glioblastoma-associated epilepsy. Moreover, experimental inhibition or deletion of GS in the entorhinal-hippocampal territory of laboratory animals causes an MTLE-like syndrome characterized by spontaneous, recurrent hippocampal-onset seizures, loss of hippocampal neurons, and in some cases comorbid depressive-like features. The goal of this review is to summarize and discuss the possible roles of astroglial GS in the pathogenesis of epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sandhu, Gruenbaum, Gruenbaum, Dhaher, Deshpande, Funaro, Lee, Zaveri and Eid.)

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188 Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188 Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188 Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.

Background: The Japanese chaff flower, Achyranthes japonica, is used as complementary medicine to control degenerative arthritis. Although commonly used in South Korea, there has been no report of side effects. We report the first case of acute interstitial nephritis (AIN) that occurred in a woman who ingested A. japonica extract for 4 months., Case Presentation: A 56-year-old Korean woman was admitted for deterioration of renal function. She had general weakness and nausea for 1 month. Her initial blood urea nitrogen and serum creatinine levels were 26.3 mg/dL and 3.2 mg/dL, respectively. She acknowledged ingesting A. japonica extract for the past 4 months. Renal histology demonstrated AIN represented by immune cell infiltration into the interstitium, tubulitis, and tubular atrophy, but the glomeruli were intact. A. japonica was discontinued immediately and conservative management was started. Renal function was nearly restored to the baseline level without medication after 13 months., Conclusion: This is a rare case report of AIN associated with a pure A. japonica extract. In the case of unknown etiology of AIN, physicians should ask about the use of herbal medicines, nutraceuticals, and traditional folk medicines including A. japonica.

The presence of a swallow-tail sign in the nigrosome-1 with hyperintense signal shown on the susceptibility-weighted imaging (SWI) has been shown to be sensitive in detecting the abnormal iron deposits in this area. A systematic evaluation in healthy subjects is required before this tool can be recommended in a widespread application. We evaluated a simple and practical SWI approach using a multiecho gradient-echo sequence with an improved contrast-to-noise ratio (CNR). We also evaluated the association of the neuromelanin imaging contrast behavior with the susceptibility and relaxation measurements. Twenty-five older and 23 young healthy adults were evaluated. The CNRs of the nigrosome-1 were compared along with method and group. Correlations of the nigrosome-1 neuromelanin signal in the neuromelanin-sensitive imaging with CNRs in the susceptibility, T1 and T2 mappings were examined. Two different coils were used to confirm the reproducibility. Compared with the single-echo, multiecho SWI can improve the CNR of the swallow-tail sign. We found significant correlations between neuromelanin signal and CNRs in the susceptibility and T2 mappings, and T1 value. The older subjects exhibited increased CNRs compared with the young adults. No significant difference was observed in the measurements between 20 and 64 channels. The multiecho technique allows the high-quality nigrosome-1 images in SWI and allows for a joint analysis of T2* and quantitative-susceptibility mapping at high spatial resolution. The correlations of neuromelanin-sensitive imaging with susceptibility and T2 imply that the iron content in the nigrosome-1 may have significant influences on the hyperintensity of neuromelanin in the magnetization transfer-related contrast.

Background and Objectives: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model., Methods: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI. Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated., Results: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the ¹H nuclear magnetic resonance analysis between groups., Conclusions: Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2021. The Korean Society of Cardiology.)

Graphene is an optimal material to be employed as an ionic diffusion barrier because of its outstanding impermeability and chemical robustness. Indium tin oxide (ITO) is often used in perovskite light-emitting diodes (PeLEDs), and it can release indium easily upon exposure to the acidic hole-injection layer so that luminescence can be quenched significantly. Here, we exploit the outstanding impermeability of graphene and use it as a chemical barrier to block the etching that can occur in ITO exposed to an acidic hole-injection layer in PeLEDs. This barrier reduced the luminescence quenching that these metallic species can cause, so the photoluminescence lifetime of perovskite film was substantially higher in devices with ITO and graphene layer (87.9 ns) than in devices that had only an ITO anode (22.1 ns). Luminous current efficiency was also higher in PeLEDs with a graphene barrier (16.4 cd/A) than in those without graphene (9.02 cd/A). Our work demonstrates that graphene can be used as a barrier to reduce the degradation of transparent electrodes by chemical etching in optoelectronic devices.

Background: The Western Pacific region constitutes one-quarter of the world's population and has diverse health needs. While dialogue on and promotion of advanced practice nurses are ongoing, this study investigated the current responsibilities of nurses in advanced roles, future healthcare needs, and the implications of these components for nurses' professional development within the Western Pacific region., Methods: This study employed three phases, a descriptive survey on the current status of nurses in advanced roles in the Western Pacific region, followed by a Delphi survey, and exploratory interviews. A total of 55 national experts with clinical, academic, and/or government-related backgrounds from 18 countries participated from December 2017 - December 2018. The descriptive survey via email to identify the status of nurses in advanced roles and a working definition was developed. This formed the basis for the Delphi survey, which identified key barriers and challenges for enhancing the development of nurses in advanced roles within the country (round 1) and for the region (rounds 2 and 3). Lastly, semi-structured individual interviews were conducted to identify strategies for establishing nurses in advanced roles to improve equitable access to healthcare., Results: Thirty-seven roles and characteristics were identified and categorized for nurses performing advanced roles. Emergency care, critical care, elderly health, child health, and rural/remote communities were identified as fields with particular need for nurses in advanced roles in the Western Pacific region. Providing effective services, influencing government leadership, and advocating for health system sustainability were deemed necessary to improve equitable healthcare access. We found that nurses in advanced roles are not limited to clinical tasks within the hospital but are poised for active participation in primary healthcare, education/teaching, professional leadership, quality management, and research., Conclusions: Demand for nurses in advanced roles is high in the Western Pacific region and 15 items were identified across five core strategic areas to enhance development of nurses in advanced roles. Governmental-level recommendations include establishing legislative protection, improving systems for remuneration, strengthening supportive channels, and conducting national needs assessments.

Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, 188 Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of 188 Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of 188 Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with 188 Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The 188 Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or 188 Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.

Formation of a zygote is coupled with extensive epigenetic reprogramming to enable appropriate inheritance of histone methylation and prevent developmental delays. In Caenorhabditis elegans , this reprogramming is mediated by the H3K4me2 demethylase SPR-5 and the H3K9 methyltransferase, MET-2. In contrast, the H3K36 methyltransferase MES-4 maintains H3K36me2/3 at germline genes between generations to facilitate re-establishment of the germline. To determine whether the MES-4 germline inheritance pathway antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two pathways. We found that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me3 and the ectopic expression of MES-4-targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that MES-4 prevents crucial germline genes from being repressed by antagonizing maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.This article has an associated 'The people behind the papers' interview., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are antihyperglycemic agents with cardioprotective properties against diabetic cardiomyopathy (DCM). However, the distinctive mechanisms underlying GLP-1RAs and SGLT2is in DCM are not fully elucidated. The purpose of this study was to investigate the impacts of GLP1RAs and/or SGLT2is on myocardial energy metabolism, cardiac function, and apoptosis signaling in DCM. Biochemistry and echocardiograms were studied before and after treatment with empagliflozin (10 mg/kg/day, oral gavage), and/or liraglutide (200 μg/kg every 12 h, subcutaneously) for 4 weeks in male Wistar rats with streptozotocin (65 mg/kg intraperitoneally)-induced diabetes. Cardiac fibrosis, apoptosis, and protein expression of metabolic and inflammatory signaling molecules were evaluated by histopathology and Western blotting in ventricular cardiomyocytes of different groups. Empagliflozin and liraglutide normalized myocardial dysfunction in diabetic rats. Upregulation of phosphorylated-acetyl coenzyme A carboxylase, carnitine palmitoyltransferase 1β, cluster of differentiation 36, and peroxisome proliferator-activated receptor-gamma coactivator, and downregulation of glucose transporter 4, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α2 to adenosine monophosphate-activated protein kinase α2, and the ratio of phosphorylated protein kinase B to protein kinase B in diabetic cardiomyocytes were restored by treatment with empagliflozin or liraglutide. Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3, interleukin-1β, tumor necrosis factor-α, and cleaved caspase-1 were significantly downregulated in empagliflozin-treated and liraglutide-treated diabetic rats. Both empagliflozin-treated and liraglutide-treated diabetic rats exhibited attenuated myocardial fibrosis and apoptosis. Empagliflozin modulated fatty acid and glucose metabolism, while liraglutide regulated inflammation and apoptosis in DCM. The better effects of combined treatment with GLP-1RAs and SGLT2is may lead to a potential strategy targeting DCM.

Nanotargeted liposomes may be modified with targeting peptide on the surface of a prepared liposome to endow specificity and elevate targeting efficiency. The aim of this study was to develop a radioactive targeted nanoparticle, the 111 In-cyclic RGDfK-liposome, and its advantage of recognizing the α V β3 integrin was examined. The cyclic RGDfK modified liposomes were demonstrated the ability to bind the α V β3 integrin expressed on the surface of human melanoma cell in vitro and in vivo. The effects of the cyclic RGDfK-liposome on the functioning of phagocytes was also examined, showing no considerable negative effects on the engulfment of bacteria and the generation of reactive oxygen species. Based upon these findings, the cyclic RGDfK- liposome is said to be a promising agent for tumor imaging.

Organic-inorganic hybrid perovskite nanoparticles (NPs) are a very strong candidate emitter that can meet the high luminescence efficiency and high color standard of Rec.2020. However, the instability of perovskite NPs is the most critical unsolved problem that limits their practical application. Here, an extremely stable crosslinked perovskite NP (CPN) is reported that maintains high photoluminescence quantum yield for 1.5 years (>600 d) in air and in harsher liquid environments (e.g., in water, acid, or base solutions, and in various polar solvents), and for more than 100 d under 85 °C and 85% relative humidity without additional encapsulation. Unsaturated hydrocarbons in both the acid and base ligands of NPs are chemically crosslinked with a methacrylate-functionalized matrix, which prevents decomposition of the perovskite crystals. Counterintuitively, water vapor permeating through the crosslinked matrix chemically passivates surface defects in the NPs and reduces nonradiative recombination. Green-emitting and white-emitting flexible large-area displays are demonstrated, which are stable for >400 d in air and in water. The high stability of the CPN in water enables biocompatible cell proliferation which is usually impossible when toxic Pb elements are present. The stable materials design strategies provide a breakthrough toward commercialization of perovskite NPs in displays and bio-related applications., (© 2020 Wiley‐VCH GmbH.)

Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the use of predictive biomarkers and stratification strategies offer opportunities to improve therapeutic success in HNSCC. To enable precision medicine of HNSCC, an understanding of the microenvironment that influences tumour growth and response to therapy is required alongside research tools that recapitulate the features of human tumours. In this review, we highlight the importance of the tumour microenvironment in HNSCC, with a focus on tumour hypoxia, and discuss the fidelity of patient-derived xenograft and organoids for modelling human HNSCC and response to therapy. We describe the benefits of patient-derived models over alternative preclinical models and their limitations in clinical relevance and how these impact their utility in precision medicine in HNSCC for the discovery of new therapeutic agents, as well as predictive biomarkers to identify patients' most likely to respond to therapy.

Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure, with an incidence of 11%. However, the disease mechanism remains unclear, and no effective treatment is available. Paricalcitol has been reported to be effective in animal models of kidney injury. We hypothesized that paricalcitol could play a renoprotective role against CI-AKI. Rats were divided into control, paricalcitol, contrast, and paricalcitol-plus-contrast groups. We used a previously published protocol to produce CI-AKI. Paricalcitol (0.3  μ g/kg) was administered intraperitoneally before 24 h and 30 min before indomethacin. We used HK-2 cells to evaluate the effects of paricalcitol on mitophagy and senescence. Ioversol triggered renal dysfunction, increasing blood urea nitrogen and serum creatinine. Significant tubular damage, increased 8-OHdG expression, and apoptosis were apparent. Ioversol injection induced high expression levels of the mitophagy markers Pink1, Parkin, and LC3 and the senescence markers β -galactosidase and p16INK4A. Paricalcitol pretreatment prevented renal dysfunction and reduced tissue damage by reducing both mitophagy and senescence. Cellular morphological changes were found, and expression of LC3B and HMGB1 was increased by ioversol in HK-2 cells. Paricalcitol countered these effects. This study showed that mitochondria might drive injury phenotypes in CI-AKI, and that paricalcitol protects against CI-AKI by decreasing mitochondrial damage., Competing Interests: The authors declare no competing interests., (Copyright © 2020 Eunjin Bae et al.)

Conventional solution-processing techniques such as the spin-coating method have been used successfully to reveal excellent properties of organic-inorganic halide perovskites (OHPs) for optoelectronic devices such as solar cell and light-emitting diode, but it is essential to explore other deposition techniques compatible with large-scale production. Single-source flash evaporation technique, in which a single source of materials of interest is rapidly heated to be deposited in a few seconds, is one of the candidate techniques for large-scale thin film deposition of OHPs. In this work, we investigated the reliability and controllability of the single-source flash evaporation technique for methylammonium lead iodide (MAPbI 3 ) perovskite. In-depth statistical analysis was employed to demonstrate that the MAPbI 3 films prepared via the flash evaporation have an ultrasmooth surface and uniform thickness throughout the 4-inch wafer scale. We also show that the thickness and grain size of the MAPbI 3 film can be controlled by adjusting the amount of the source and number of deposition steps. Finally, the excellent large-area uniformity of the physical properties of the deposited thin films can be transferred to the uniformity in the device performance of MAPbI 3 photodetectors prepared by flash evaporation which exhibited the responsivity of 0.2 A/W and detectivity of 3.82 × 10 11 Jones.

Few studies focus on Registered Nurse (RN) staffing and resident health outcomes in Korean nursing homes. This study aimed to investigate the effects of RN staffing on quality of care and resident outcomes in South Korean nursing homes. The study was a secondary data analysis of 5679 participants from the National Health Insurance Service. A mixed-effect linear model and multinomial logistic regression model assessed resident outcomes and quality of care, respectively. The number of RNs significantly affected patient mortality. The overall evaluation rating for quality of care in nursing homes increased as the number of RNs increased. Level of RN staffing in nursing homes influenced health management and quality of care for residents. A variety of efforts are needed to strengthen the workforce of RNs in nursing homes, including enacting a law for safe RN staffing and converting the evaluation of nursing home quality into health outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. All authors have no financial relationships relevant to this article to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational pollutants derived from incomplete combustion of organic materials, including wood and fossil fuels. Epidemiological studies have evaluated the association between PAH exposure and hypertension or cardiovascular disease in the general population, but the evidence is limited. In this study, we evaluated the association between urinary PAH metabolites and hypertension in the Korean adult population. A total of 6478 adults who participated in the Second Korean National Environmental Health Survey (2012-2014) were included. The differences in urinary concentrations of four PAH metabolites, including 1-hydroxypyrene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 2-naphthol, were compared according to hypertension status using a general linear model. Adjusted odds ratios (aORs) for hypertension were calculated according to the quartile groups of urinary PAH metabolites after adjusting for age, sex, body mass index (BMI), smoking, and alcohol consumption in multiple logistic regression analyses. The estimated mean concentrations of urinary 1-hydroxyphenanthrene were significantly higher in the hypertension group than in the non-hypertension group. In 1-hydroxyphenanthrene, the OR for hypertension was significantly higher in the third and fourth quartile groups than in the first quartile group (third: OR 1.707, 95% CI 1.203-2.423, fourth: OR 1.604, 95% CI 1.158-2.223). No significant associations were detected for the other metabolites. Our results suggest an association between exposure to PAHs and hypertension in a Korean adult population. Further studies are required to evaluate the effects of low-dose long-term exposure to PAHs on hypertension and cardiovascular disease.

Existing gels are mostly polar, whose nature limits their role in soft devices. The intermolecular interactions of nonpolar polymer-liquid system are typically weak, which makes the gel brittle. Here we report highly soft and transparent nonpolar organogels. Even though their elements are only carbon and hydrogen, their elastic modulus, transparency, and stretchability are comparable to common soft hydrogels. A key strategy is introducing aromatic interaction into the polymer-solvent system, resulting in a high swelling ratio that enables efficient plasticization of the polymer networks. As a proof of applicability, soft perovskite nanocomposites are synthesized, where the nonpolar environment of organogels enables stable formation and preservation of highly concentrated perovskite nanocrystals, showing high photoluminescence efficiency (~99.8%) after water-exposure and environmental stabilities against air, water, acid, base, heat, light, and mechanical deformation. Their superb properties enable the demonstration of soft electroluminescent devices that stably emit bright and pure green light under diverse deformations.

Background: The association between lower serum sodium levels and the clinical outcomes of insomnia patients remains unclear. We explored whether lower serum sodium is associated with poor clinical outcomes in patients with insomnia., Methods: We retrospectively enrolled patients with a diagnosis of insomnia from January 2011 to December 2012. We divided participants into three groups according to initial serum sodium level: tertile 1 (< 138 mmol/L), tertile 2 (138.0-140.9 mmol/L), and tertile 3 (≥ 141.0 mmol/L). To calculate the relative risk of death, hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using Cox proportional hazard models., Results: A total of 412 patients with insomnia were included, of whom 13.6% (n = 56) had hyponatremia. Patients with lower serum sodium concentrations were older and had lower hemoglobin, calcium, phosphorus, and albumin levels. At the median follow-up of 49.4 months, 44 patients had died and 62 experienced acute kidney injury (AKI). Kaplan-Meier analysis showed significantly higher mortality in patients in the lowest tertile for serum sodium. The lowest tertile of the serum sodium level and the AKI were associated with all-cause mortality. However, the lowest tertile of the serum sodium level was not significantly associated with AKI., Conclusions: The lowest tertile of the serum sodium level was associated with a higher mortality rate in insomnia patients. Our results suggest that the serum sodium level could serve as a prognostic factor in insomniacs; patients with lower sodium levels require particular care.

The low sheet resistance and high optical transparency of silver nanowires (AgNWs) make them a promising candidate for use as the flexible transparent electrode of light-emitting diodes (LEDs). In a perovskite LED (PeLED), however, the AgNW electrode can react with the overlying perovskite material by redox reactions, which limit the electroluminescence efficiency of the PeLED by causing the degradation of and generating defect states in the perovskite material. In this study, we prepared Ag-Ni core-shell NW electrodes using the solution-electroplating technique to realize highly efficient PeLEDs based on colloidal formamidinium lead bromide (FAPbBr 3 ) nanoparticles (NPs). Solvated Ni ions from the NiSO 4 source were deposited onto the surface of AgNW networks in three steps: (i) cathodic cleaning, (ii) adsorption of the Ni-ion complex onto the AgNW surface, and (iii) uniform electrodeposition of Ni. An ultrathin (∼3.5 nm) Ni layer was uniformly deposited onto the AgNW surface, which exhibited a sheet resistance of 16.7 Ω/sq and an optical transmittance of 90.2%. The Ag-Ni core-shell NWs not only increased the work function of the AgNW electrode, which facilitated hole injection into the emitting layer, but also suppressed the redox reaction between Ag and FAPbBr 3 NPs, which prevented the degradation of the emitting layer and the generation of defect states in it. The resulting PeLEDs based on FAPbBr 3 NPs with the Ag-Ni core-shell NWs showed high current efficiency of 44.01 cd/A, power efficiency of 35.45 lm/W, and external quantum efficiency of 9.67%.

Conventional organic light-emitting devices without an encapsulation layer are susceptible to degradation when exposed to air, so realization of air-stable intrinsically-stretchable display is a great challenge because the protection of the devices against penetration of moisture and oxygen is even more difficult under stretching. An air-stable intrinsically-stretchable display that is composed of an intrinsically-stretchable electroluminescent device (SELD) integrated with a stretchable color-conversion layer (SCCL) that contains perovskite nanocrystals (PeNCs) is proposed. PeNCs normally decay when exposed to air, but they become resistant to this decay when dispersed in a stretchable elastomer matrix; this change is a result of a compatibility between capping ligands and the elastomer matrix. Counterintuitively, the moisture can efficiently passivate surface defects of PeNCs, to yield significant increases in both photoluminescence intensity and lifetime. A display that can be stretched up to 180% is demonstrated; it is composed of an air-stable SCCL that down-converts the SELD's blue emission and reemits it as green. The work elucidates the basis of moisture-assisted surface passivation of PeNCs and provides a promising strategy to improve the quantum efficiency of PeNCs with the aid of moisture, which allows PeNCs to be applied for air-stable stretchable displays., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multiple ultrashort laser pulses are widely used in optical spectroscopy, optoelectronic manipulation, optical imaging and optical signal processing etc. The laser pulse multiplication, so far, is solely realized by using the optical setups or devices to modify the output laser pulse from the optical gain medium. The employment of these external techniques is because the gain medium itself is incapable of modifying or multiplying the generated laser pulse. Herein, with single femtosecond laser pulse excitation, we achieve the double-pulsed stimulated emission with pulse duration of around 40 ps and pulse interval of around 70 ps from metal-halide perovskite multiple quantum wells. These unique stimulated emissions originate from one fast vertical and the other slow lateral high-efficiency carrier funneling from low-dimensional to high-dimensional quantum wells. Furthermore, such gain medium surprisingly possesses nearly Auger-free stimulated emission. These insights enable us a fresh approach to multiple the ultrashort laser pulse by gain medium.

Perovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation.

Objectives: Despite the rise in community health problems in populations living in urban slums, activities of community health nurses are limited in Bangladesh. This study aimed to describe how a nurse-managed health center (NMHC) was developed in Dhaka, Bangladesh., Design: An exploratory-descriptive research design was used., Sample and Measurements: The commitment phase was conducted to establish partnerships in the community. Involvement of community leaders and members and partnerships with various organizations were established successfully in the commitment phase. The assessment phase was completed by implementing personal interviews, community site visits, and household surveys of 172 households in the community. Action plans were developed and strategies were followed to change the community during the planning phase., Results: Household survey results showed that community people suffered from non-communicable diseases, risk behaviors, and inadequate housing conditions. The high-priority community needs included nutrition and chronic management services, behavior change programs, and a clean environment. Action plans for health programs based on community needs and strategies such as securing manpower and equipment were developed., Conclusions: The systematic process of creating a NMHC, and the necessity of the community health nurse's role in responding to health needs of the urban poor in Dhaka, Bangladesh was confirmed., (© 2020 Wiley Periodicals LLC.)

Nuclear medicine is a routine but essential clinical option for diagnostic imaging and disease treatment. Encapsulating radioisotopes in injectable biodegradable hydrogels is ideal for localizing radiation sources to target tissues or organs to achieve long-term, low-dose radiotherapy. However, difficulties in the on-site production of radioactive gels upon treatment and the unpredictable radiation level at the target region are major obstacles to their clinical use. In this study, we bypassed these limitations by developing locally injectable hydrogel microparticles based on 131 I-labeled photo-crosslinkable hyaluronic acid (HA) and a microfluidic high-throughput droplet generator. This approach enabled rapid on-site production of injectable, radioactive, biodegradable (IRB) HA microgels, thus allowing their immediate therapeutic application with improved local retention and predictable radioactivity. We demonstrated the clinical utility of this comprehensive approach by preparing IRB HA microgels within 15 min and localizing them to the target tissue (rat muscle) with minimal off-target biodistribution and in vivo radioactivity that extended beyond 3 weeks., (Copyright © 2020. Published by Elsevier B.V.)

Although several transparent conducting materials such as carbon nanotubes, graphene, and conducting polymers have been intensively explored as flexible electrodes in optoelectronic devices, their insufficient electrical conductivity, low work function, and complicated electrode fabrication processes have limited their practical use. Herein, a 2D titanium carbide (Ti 3 C 2 ) MXene film with transparent conducting electrode (TCE) properties, including high electrical conductivity (≈11 670 S cm -1 ) and high work function (≈5.1 eV), which are achieved by combining a simple solution processing with modulation of surface composition, is described. A chemical neutralization strategy of a conducting-polymer hole-injection layer is used to prevent detrimental surface oxidation and resulting degradation of the electrode film. Use of the MXene electrode in an organic light-emitting diode leads to a current efficiency of ≈102.0 cd A -1 and an external quantum efficiency of ≈28.5% ph/el, which agree well with the theoretical maximum values from optical simulations. The results demonstrate the strong potential of MXene as a solution-processable electrode in optoelectronic devices and provide a guideline for use of MXenes as TCEs in low-cost flexible optoelectronic devices., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: This is a methodological study that aims to develop performance indicators based on a balanced scorecard for the clinical research coordinator (CRC) position., Methods: The CRC performance indicators were developed through a literature review, a data review, expert consultations, focus group interviews, and content validity verification. We also used these data to confirm whether the performance indicators were appropriately indexed., Results: We developed 10 strategies and 31 performance management indicators based on the 4 perspectives of the balanced scorecard (financial, customer, internal business process, and learning and growth)., Conclusions: This research developed CRC performance indicators using a balanced scorecard in order to improve the quality of CRC work performance. These indicators establish the direction that tasks should take; they motivate CRCs by being associated with the compensation system, competence development programs, and a balanced performance evaluation system.

Background: Fenoverine is a spasmolytic drug that has been used to treat abdominal pain. Although sporadic case reports or case series of rhabdomyolysis associated with fenoverine have been published, there are no studies evaluating the incidence, risk factors, and clinical outcomes of rhabdomyolysis associated with fenoverine prescription., Methods: We retrospectively reviewed the medical records of 22 patients admitted with rhabdomyolysis associated with fenoverine from January 1999 to December 2014, while excluding other well-known risk factors of rhabdomyolysis. This period was subdivided into two periods, January 1999-December 2007 and January 2008-December 2014. We analyzed the clinical and laboratory characteristics, and the prognosis of fenoverine associated with rhabdomyolysis for these times., Results: The incidence of rhabdomyolysis associated with fenoverine was 0.27% during the total period (22/8257), 0.34% in the first period (18/5298), and 0.14% in the second period (4/2959) (p < 0.001). Rhabdomyolysis occurred in 19 liver cirrhosis (LC) patients (2.03%), whereas only 3 cases (0.04%) occurred in non-LC patients (p < 0.001). Drug duration, total dose, muscle enzymes, and clinical characteristics were not different between the LC and non-LC groups. Acute renal failure (ARF) occurred in 5 patients in the LC group and 2 patients in the non-LC group (p = 0.227). Severity of hepatic derangement according to the Child-Pugh classification was not different between the ARF group and non-ARF group (p = 0.227). Four patients died, having complications of oliguric ARF (p = 0.005) and underlying severe LC (p = 0.017). Higher serum lactate dehydrogenase, blood urea nitrogen, creatinine, and potassium levels but lower serum sodium levels were found in the group that died (p = 0.001)., Conclusions: Physicians should carefully prescribe fenoverine because it may cause rhabdomyolysis, especially in patients with LC.

Flexible neuromorphic electronics that emulate biological neuronal systems constitute a promising candidate for next-generation wearable computing, soft robotics, and neuroprosthetics. For realization, with the achievement of simple synaptic behaviors in a single device, the construction of artificial synapses with various functions of sensing and responding and integrated systems to mimic complicated computing, sensing, and responding in biological systems is a prerequisite. Artificial synapses that have learning ability can perceive and react to events in the real world; these abilities expand the neuromorphic applications toward health monitoring and cybernetic devices in the future Internet of Things. To demonstrate the flexible neuromorphic systems successfully, it is essential to develop artificial synapses and nerves replicating the functionalities of the biological counterparts and satisfying the requirements for constructing the elements and the integrated systems such as flexibility, low power consumption, high-density integration, and biocompatibility. Here, the progress of flexible neuromorphic electronics is addressed, from basic backgrounds including synaptic characteristics, device structures, and mechanisms of artificial synapses and nerves, to applications for computing, soft robotics, and neuroprosthetics. Finally, future research directions toward wearable artificial neuromorphic systems are suggested for this emerging area., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Like breadcrumbs in the forest, cotranscriptionally acquired histone methylation acts as a memory of prior transcription. Because it can be retained through cell divisions, transcriptional memory allows cells to coordinate complex transcriptional programs during development. However, if not reprogrammed properly during cell fate transitions, it can also disrupt cellular identity. In this review, we discuss the consequences of failure to reprogram histone methylation during three crucial epigenetic reprogramming windows: maternal reprogramming at fertilization, embryonic stem cell (ESC) differentiation, and the continuous maintenance of cell identity in differentiated cells. In addition, we discuss how following the wrong breadcrumb trail of transcriptional memory provides a framework for understanding how heterozygous loss-of-function mutations in histone-modifying enzymes may cause severe neurodevelopmental disorders., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Photonic synapses combine sensing and processing in a single device, so they are promising candidates to emulate visual perception of a biological retina. However, photonic synapses with wavelength selectivity, which is a key property for visual perception, have not been developed so far. Herein, organic photonic synapses that selectively detect UV rays and process various optical stimuli are presented. The photonic synapses use carbon nitride (C 3 N 4 ) as an UV-responsive floating-gate layer in transistor geometry. C 3 N 4 nanodots dominantly absorb UV light; this trait is the basis of UV selectivity in these photonic synapses. The presented devices consume only 18.06 fJ per synaptic event, which is comparable to the energy consumption of biological synapses. Furthermore, in situ modulation of exposure to UV light is demonstrated by integrating the devices with UV transmittance modulators. These smart systems can be further developed to combine detection and dose-calculation to determine how and when to decrease UV transmittance for preventive health care., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Although the quality of postoperative recovery may be affected by factors, there are few investigations whether the type of anesthesia also affects it. In this single-blinded, prospective, observational study, we compared the quality of postoperative recovery in patients undergoing orthopedic forearm surgery under general or regional anesthesia (brachial plexus block)., Methods: Ninety-seven subjects, aged 18-65 years and American Society of Anesthesiologists physical status I or II, undergoing orthopedic forearm surgery, were allocated to general or regional anesthesia group. The quality of postoperative recovery was assessed using a validated Korean version of Quality of Recovery-40 (QoR-40K) questionnaire. Patients were surveyed three times, the day before surgery (baseline) and 1st and 7th day after the surgery, and the scores of both groups were compared., Results: We analyzed 47 and 50 patients in general and regional anesthesia, respectively. The global QoR-40K score and those of each of its five dimensions were not significantly different between the two groups at baseline, 1st and 7th day postoperatively. In two-way RM ANOVA, the global QoR-40K score at postoperative 1st day was significantly lower than that of baseline (P < 0.001) and postoperative 7th day (P < 0.001), respectively, in both general and regional anesthesia groups. However, there was no significant difference at each timepoint between the two groups., Conclusions: The present study suggests that brachial plexus block with intravenous dexmedetomidine infusion does not improve the quality of postoperative recovery compared to sevoflurane inhalation anesthesia with remifentanil infusion in patients undergoing orthopedic forearm surgery.

Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.

In Caenorhabditis elegans , mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Here, we show that wdr-5 mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. In addition, we find that the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2, and can be recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. Finally, we show that the transgenerational acquisition of longevity in jhdm-1 mutants is associated with accumulating genomic H3K9me2 that is inherited by their long-lived wild-type descendants at a subset of loci. These results suggest that heterochromatin facilitates the transgenerational establishment and inheritance of a complex trait. Based on these results, we propose that transcription-coupled H3K4me via COMPASS limits lifespan by encroaching upon domains of heterochromatin in the genome., Competing Interests: TL, HD, AE, BC, DK No competing interests declared, (© 2019, Lee et al.)

Background and purpose: Poly(ADP-ribose)polymerase-1 (PARP1) and DNA-dependent protein kinase (DNA-PK) play key roles in the repair of radiation-induced DNA double strand breaks, but it is unclear which is the preferred therapeutic target in radiotherapy. Here we compare small molecule inhibitors of both as radiosensitizers of head and neck squamous cell carcinoma (HNSCC) cell lines. Methods: Two PARP1 inhibitors (olaparib, veliparib) and two DNA-PK inhibitors (KU57788, IC87361) were tested in 14 HNSCC cell lines and two non-tumorigenic lines (HEK-293 and WI-38/Va-13), with drug exposure for 6 or 24 h post-irradiation, using regrowth assays. For three lines (UT-SCC-54C, -74B, -76B), radiosensitization was also assessed by clonogenic assay under oxia and acute (6 h) anoxia, and for 54C cells under chronic hypoxia (0.2% O 2 for 48 h). Relationships between sensitizer enhancement ratios (SER) and gene expression, assessed by RNA sequencing, were evaluated. Results: The inhibitors were minimally cytotoxic in the absence of radiation, with 74B and 54C cells the most sensitive to both olaparib and KU57788. Median SER values for each inhibitor at 1.1 µM were 1.12 (range 1.02-1.24) for olaparib, 1.08 (1.04-1.13) for veliparib, 1.35 (1.10-1.64) for IC87361 and 1.77 (1.41-2.38) for KU57788. The higher SER values for the DNA-PK inhibitors were observed with all cell lines (except HEK-293) and all concentrations tested and were confirmed by clonogenic assay. Radiosensitization by the DNA-PK inhibitors correlated with expression of SLFN11 mRNA. Radiosensitization by IC87361 and olaparib was significantly enhanced under acute anoxia and chronic hypoxia. Conclusions: The DNA-PK inhibitors KU57788 and IC87361 are more effective radiosensitizers than the PARP-1 inhibitors olaparib and veliparib at non-cytotoxic concentrations in HNSCC cell cultures and their activity is enhanced by SLFN11 and hypoxia.

Background: There is growing recognition of the importance of educating health professional students to enhance their competence in collaborating with individuals from other health professions in the area of global health. This study aimed to identify the performance levels in interprofessional global health competencies (IGHC) of health professional students, their educational needs, and the strategies for successfully developing IGHC., Methods: This study used a mixed methods design involving an online survey followed by focus group interviews. A sample of 325 fourth-year undergraduate students from 14 health-related majors completed a self-report online survey (38.8% response rate). The performance of IGHC was measured on a five-point Likert scale using the IGHC items developed by the Consortium of Universities for Global Health. Additionally, 12 senior students and five professors in global health-related majors participated in focus group interviews. The students' educational needs and priorities were analysed using the Borich needs assessment and the Locus for Focus model., Results: The participants' IGHC mean score was 3.11 (SD = 0.55) and differed by previous global health activity experiences (t = - 2.10, p = .037). Nine competencies in six domains using the Locus for Focus model were identified as a priority for global health education. Suggested strategies to enhance IGHC included establishing IGHC education in formal curricula, developing value-based content and outcomes, and engaging students in learning activities., Conclusions: It is necessary to design an interprofessional pre-departure course to achieve the priority IGHC and to organise learning activities where there is cooperation in problem solving while applying the expertise of each major within resource-limited settings. This study supports future health professional education that should foster enhanced roles and scopes of practice as changing agents to assure the achievement of sustainable development goals.

The use of colistin in the treatment of multidrug-resistant Gram-negative bacterial infections is restricted due to nephrotoxicity. We investigated the effects of aged black garlic extract (ABGE) on colistin-induced kidney injury in rats. Rats were assigned to four groups. Normal saline was intraperitoneally and intragastrically injected for control group. ABGE was intragastrically injected for garlic group. Ten mg/kg of colistin was intraperitoneally injected for 6 consecutive days for colistin group. One percent of ABGE was done 30 min prior to colistin injection for treatment group. Rats were sacrificed on the next day after last colistin injection. Colistin injection increased the serum levels of blood urea nitrogen and creatinine; however, ABGE prevented deterioration of these serum levels. ABGE also alleviated tubular damage, including vacuolation and necrosis. TUNEL-positive cells were observed less frequently for the ABGE-treated groups. CD68 positive cells were significantly decreased by pretreatment with ABGE. Levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine and malondialdehyde were lower in the ABGE-treated groups. Levels of NF-κB, inducible NO synthase, COX-2, and TGF-β1 were lower in rats that had been treated with ABGE injection. Renal levels of IL-1β and TNF-α were increased by colistin administration whereas renal SOD, catalase, and GSH levels were restored by ABGE administration. These results suggest that ABGE, which has antioxidant and anti-inflammatory properties, might be a potential therapeutic agent to prevent renal toxicity of colistin.

Acute kidney injury (AKI) associated with acute pyelonephritis (APN) rarely has been reported. The aim of this study was to evaluate the incidence and risk factors of AKI associated with APN. We retrospectively reviewed the medical records of 403 patients over 18-year old age hospitalized for APN management from October 2009 to September 2014 in tertiary care referral center. Demographic data, clinical symptoms and signs, and laboratory findings were gathered from the medical records and analyzed. The mean age of patients was 57 years and APN commonly occurred in female (87.6%). AKI occurred in 253 patients (62.8%). As per the RIFLE classification, renal injury was graded as 'Risk' (62.1%), 'Injury' (26.5%), and 'Failure' (11.4%). AKI patients were more likely a male gender and had complicated APN. The AKI group had a significantly higher tendency to present with shock. The prevalence of underlying chronic kidney disease (CKD) was significantly higher in the AKI group. There was no difference in mortality between the AKI and non-AKI groups. Multivariate analysis revealed that age over 65 (OR 1.93, 95% CI 1.18-3.13, p= .008), complicated (OR 2.13, 95% CI 1.35-3.34, p= .001) and bilateral APN (OR 1.71, 95% CI 1.01-2.88, p= .045), and initial shock (OR 2.44, 95% CI 1.05-5.71, p= .039) were independent risk factors for the occurrence of AKI in patients with APN. Physicians should attempt to prevent, detect, and manage AKI associated with APN in patients with above conditions.

Tumour necrosis factor (TNF)-α induces cardiac metabolic disorder and mitochondrial dysfunction. Hydrogen sulphide (H 2 S) contains anti-inflammatory and biological effects in cardiomyocytes. This study investigated whether H 2 S modulates TNF-α-dysregulated mitochondrial function and metabolism in cardiomyocytes. HL-1 cells were incubated with TNF-α (25 ng/mL) with or without sodium hydrosulphide (NaHS, 0.1 mmol/L) for 24 hours. Cardiac peroxisome proliferator-activated receptor (PPAR) isoforms, pro-inflammatory cytokines, receptor for advanced glycation end products (RAGE) and fatty acid metabolism were evaluated through Western blotting. The mitochondrial oxygen consumption rate and adenosine triphosphate (ATP) production were investigated using Seahorse XF24 extracellular flux analyzer and bioluminescence assay. Fluorescence intensity using 2', 7'-dichlorodihydrofluorescein diacetate was used to evaluate mitochondrial oxidative stress. NaHS attenuated the impaired basal and maximal respiration, ATP production and ATP synthesis and enhanced mitochondrial oxidative stress in TNF-α-treated HL-1 cells. TNF-α-treated HL-1 cells exhibited lower expression of PPAR-α, PPAR-δ, phosphorylated 5' adenosine monophosphate-activated protein kinase-α2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase-1, PPAR-γ coactivator 1-α and diacylglycerol acyltransferase 1 protein, but higher expression of PPAR-γ, interleukin-6 and RAGE protein than control or combined NaHS and TNF-α-treated HL-1 cells. NaHS modulates the effects of TNF-α on mitochondria and the cardiometabolic system, suggesting its therapeutic potential for inflammation-induced cardiac dysfunction., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

The cellular, molecular, and metabolic mechanisms that underlie the development of mesial temporal lobe epilepsy are incompletely understood. Here we review the role of astrocytes in epilepsy development (a.k.a. epileptogenesis), particularly astrocyte pathologies related to: aquaporin 4, the inwardly rectifying potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, excitatory amino acid transporters EAAT1 and EAAT2, and glutamine synthetase. We propose that inhibition, dysfunction or loss of astrocytic glutamine synthetase is an important causative factor for some epilepsies, particularly mesial temporal lobe epilepsy and glioblastoma-associated epilepsy. We postulate that the regulatory mechanisms of glutamine synthetase as well as the downstream effects of glutamine synthetase dysfunction, represent attractive, new targets for antiepileptogenic interventions. Currently, no antiepileptogenic therapies are available for human use. The discovery of such interventions is important as it will fundamentally change the way we approach epilepsy by preventing the disease from ever becoming manifest after an epileptogenic insult to the brain., (© 2019 Wiley Periodicals, Inc.)

Metal-halide perovskites (MHPs) are well suited to be vivid natural color emitters due to their superior optical and electrical properties, such as narrow emission linewidths, easily and widely tunable emission wavelengths, low material cost, and high charge carrier mobility. Since the first development of MHP light-emitting diodes (PeLEDs) in 2014, many researchers have tried to understand the properties of MHP emitters and the limitations to luminescence efficiency (LE) of PeLEDs, and have devoted efforts to increase the LE of MHP emitters and PeLEDs. Within three and half years, PeLEDs have shown rapidly increased LE from external quantum efficiency ≈0.1% to ≈14.36%. Herein, the factors that limit the LE of PeLEDs are reviewed; the factors are characterized into the following groups: i) photophysical properties of MHP crystals, ii) morphological factors of MHP layers, and iii) problems caused by device architectures. Then, the strategies to overcome those luminescence-limiting factors in MHP emitters and PeLEDs are critically evaluated. Finally, research directions to further increase the LE of MHP emitters and the potential of MHPs as a core component in next-generation displays and solid-state lightings are suggested., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)