Observation of the exceptional-point-enhanced Sagnac effect.

Exceptional points (EPs) are special spectral degeneracies of non-Hermitian Hamiltonians that govern the dynamics of open systems. At an EP, two or more eigenvalues, and the corresponding eigenstates, coalesce1-3. Recently, it was predicted that operation of an optical gyroscope near an EP results in improved response to rotations4,5. However, the performance of such a system has not been examined experimentally. Here we introduce a precisely controllable physical system for the study of non-Hermitian physics and nonlinear optics in high-quality-factor microresonators. Because this system dissipatively couples counter-propagating lightwaves within the resonator, it also functions as a sensitive gyroscope for the measurement of rotations. We use our system to investigate the predicted EP-enhanced Sagnac effect4,5 and observe a four-fold increase in the Sagnac scale factor by directly measuring rotations applied to the resonator. The level of enhancement can be controlled by adjusting the system bias relative to the EP, and modelling results confirm the observed enhancement. Moreover, we characterize the sensitivity of the gyroscope near the EP. Besides verifying EP physics, this work is important for the understanding of optical gyroscopes.

Cardiac-to-Bronchial Fistula in Hepatocellular Carcinoma: A Case Report.

Hepatocellular carcinoma (HCC) stands as a significant contributor to cancer-related mortality globally. While the acute and often fatal manifestations of locally advanced HCC primarily present within the abdomen, it is crucial to recognize that the respiratory and circulatory systems can also fall victim due to the liver's unique anatomical position within the body. Here, we present the case of a 63-year-old male recently diagnosed with locally advanced HCC with vascular invasion. Shortly after receiving target therapy and focal radiotherapy, the patient developed repeated secondary infections and a persistent diaphragmatic defect. As the necrotic tissue invaded the pleural space, subsequent tumor-to-bronchial and tumor-to-cardiac fistulas emerged, resulting in an abnormal connection between the respiratory and cardiovascular systems, leading to massive air emboli in circulation. This report highlights the risk of supradiaphragmatic complications in HCC patients with post-treatment secondary infections, particularly in patients predisposed to developing diaphragmatic defects.

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia.

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Thrombospondin 1-induced exosomal proteins attenuate hypoxia-induced paraptosis in corneal epithelial cells and promote wound healing.

Thrombospondin-1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia-induced damages and wound-healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography-tandem mass spectrometry, and HCE cell migration and motility were examined through wound-healing assay and time-lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2 -induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing-associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia-induced damages and inhibited paraptosis progression by promoting cell migration, cell-cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia-induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia-associated corneal diseases.

Effectiveness of Multidisciplinary Care for Chronic Kidney Disease: A Systematic Review.

BACKGROUND: Chronic kidney disease (CKD) is a common chronic disease. As this disease is extremely complex, multidisciplinary care (MDC) is needed to provide complete and continuous care. AIM: A systematic literature review was performed to examine the constituents of MDC, the content of MDC interventions, and the health outcomes in CKD patients receiving MDC. METHODS: Searches of five Chinese and English databases for studies of CKD patients who had received MDC from 2007 to 2019 revealed 11 studies, which comprised 16,066 CKD patients. The Physiotherapy Evidence Database scale (Physiotherapy Evidence Database, 2017) was used to appraise study quality for randomized controlled trials, and the Joanna Briggs Institute Critical Appraisal tools (Joanna Briggs Institute, 2017) were for cohort studies. RESULTS: The MDC teams that provided comprehensive medical care for these patients included nephrologists, nurses, surgeons, general practitioners, pharmacists, psychotherapists, social workers, nutritionists, and other specialists. The literature review revealed that MDC for CKD slows the decline in estimated glomerular filtration rate and decreases patient mortality, the risk of renal replacement therapy, the need for emergent dialysis, and annual medical costs. Analyses of biochemical markers in the CKD patients showed that MDC improves control of serum levels of calcium and phosphate, improves control of parathyroid hormone, and reduces proteinuria and fasting blood glucose values. However, further studies are needed to determine the effects of MDC on all-cause mortality, blood pressure control, hospitalization rate, hospitalization for cardiovascular or infection events, medications use, and other biochemical markers in CKD patients. LINKING EVIDENCE TO ACTION: Cross-disciplinary collaboration of healthcare professionals is needed to ensure that patients undergo regular follow-up and periodic assessment of clinical status, in addition to ensuring that relevant resources and assistance are provided in a timely manner. A follow-up period of at least 2 years is also needed to ensure sufficient time to observe MDC results.

Fiber taper characterization by optical backscattering reflectometry.

Fiber tapers provide a way to rapidly measure the spectra of many types of optical microcavities. Proper fabrication of the taper ensures that its width varies sufficiently slowly (adiabatically) along the length of the taper so as to maintain single spatial mode propagation. This is usually accomplished by monitoring the spectral transmission through the taper. In addition to this characterization method it is also helpful to know the taper width versus length. By developing a model of optical backscattering within the fiber taper, it is possible to use backscatter measurements to characterize the taper width versus length. The model uses the concept of a local taper numerical aperture to accurately account for varying backscatter collection along the length of the taper. In addition to taper profile information, the backscatter reflectometry method delineates locations along the taper where fluctuations in fiber core refractive index, cladding refractive index, and taper surface roughness each provide the dominant source of backscattering. Rayleigh backscattering coefficients are also extracted by fitting the data with the model and are consistent with the fiber manufacturer's datasheet. The optical backscattering reflectometer is also used to observe defects resulting from microcracks and surface contamination. All of this information can be obtained before the taper is removed from its fabrication apparatus. The backscattering method should also be prove useful for characterization of nanofibers.

Ocular genetics in Taiwan.

PURPOSE OF REVIEW: Ocular genetics is an emerging specialty which has accompanied the advancement of modern genetic technology. This review is to understand the current status of practice in ocular genetics in Taiwan. RECENT FINDINGS: There is only one ocular genetics clinic in Taiwan. Certified clinical laboratories provide few gene tests in ocular genetics. Most ocular genetic study is focused on myopia. Financial obstacles are a major problem for patients to seek gene tests. SUMMARY: Despite a relatively successful, healthcare system in Taiwan, when compared with developed countries, ocular genetics is at an early stage of development. More financial resources and labor are needed to advance clinical care and research.

Hypoxia-induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia-inducible factors-1α protein.

BACKGROUND: Hypoxia is the most important stimulus leading to up-regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia-inducible factors-1α (HIF-1α) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF-1α in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia. METHOD: An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2 ) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF-1α were measured by ELISA kits and RT-PCR, respectively. RESULT: Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF-1α protein in RPE cells (P < 0.05). Melatonin at 10-5 to 10-8 M significantly inhibited hypoxia-induced expression, the secretion of VEGF and the accumulation of HIF-1α protein (P < 0.05), but not affected expression of VEGF and HIF-1α under normoxia (P > 0.05). CONCLUSION: This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis.

Early onset ectopia lentis due to a FBN1 mutation with non-penetrance.

Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene. We report on a family with ectopia lentis. The propositus is a 6-year-old boy with bilateral superior-temporal ectopia lentis. His echocardiogram was normal and he did not meet the revised Ghent criteria for Marfan syndrome. Molecular genetic testing revealed c.1948 C>T (p.Arg650Cys) in FBN1. The mother has visual acuity of 20/20 with -4.50 right eye and -2.50 left eye. She has no evidence of ectopia lentis. DNA analysis revealed that she has the same FBN1 mutation. Seven other maternal family members also have ectopia lentis. In conclusion, we report on a case of early-onset autosomal dominant isolated ectopia lentis caused by FBN1 mutation that has previously been reported only in Marfan syndrome. The child's mother presumably represents a rare case of nonpenetrance.

A novel gene mutation in a family with X-linked retinoschisis.

BACKGROUND/PURPOSE: To describe the clinical characteristics of a Taiwanese family with X-linked retinoschisis (XLRS) and to investigate the molecular genetics of a novel mutation in the retinoschisin 1 (RS1) gene. METHODS: A total of 15 participants in this XLRS family were analyzed. Complete ophthalmic examinations and fundus photography were performed on 15 family members. These tests identified five affected males and two female carriers. Blood samples were collected, and genomic DNA was extracted. Best-corrected visual acuity, optical coherence tomography (OCT), electroretinogram (ERG), and direct DNA sequence analysis of the RS1 gene were performed on 15 family members. RESULTS: Five affected males, with visual acuity ranging from 0.2 to 0.7, had macular schisis and abnormal retinal pigment epithelium pigmentation. The mixed scotopic ERG "b" wave was more reduced than the "a" wave. OCT revealed typical microcystic schisis cavities within the macula area. Direct DNA sequence analysis revealed a single base pair deletion, 97delT, in all the affected individuals. This deletion resulted in a frameshift mutation of the RS1 gene, causing protein truncation. The affected males in this family showed moderately decreased visual acuity and dysfunction in both cone cells and phototransduction. CONCLUSION: We identified a novel RS1 (97delT) mutation in a Taiwanese family with XLRS. This finding expands the RS1 mutation spectrum and may help to further understand the molecular pathogenesis of XLRS.

Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging.

In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples.

Uncorrected visual acuity and noncycloplegic autorefraction predict significant refractive errors in Taiwanese preschool children.

PURPOSE: To investigate the accuracy of uncorrected visual acuity (UCVA), stereopsis, and noncycloplegic autorefraction (NCAR) tests performed by vision-screening technicians and to determine the best referral criteria when using these methods to screen for significant refractive errors in preschool children. DESIGN: Retrospective, case-control, and cross-sectional study. PARTICIPANTS: We reviewed 1000 records for a population-based preschool vision-screening program. The target conditions were defined as myopia ≤-3.0 diopters (D), hyperopia ≥ 4.5 D, astigmatism ≥ 2.0 D, and anisometropia ≥ 2.0 D. METHODS: Receiver operating characteristic (ROC) curve was used to calculate optimal referral cutoff values. The examination results obtained by the vision-screening technicians were compared with those obtained by a pediatric ophthalmologist, which were considered the gold standard. MAIN OUTCOME MEASURES: The efficacies (sensitivity, specificity, positive predictive value, and negative predictive value) of different tests were evaluated. RESULTS: In 7.0% (95% confidence interval [CI], 5.3-8.7) of the children, at least 1 eye showed 1 of the target conditions. If only the right eyes were considered, the prevalence of target conditions was 4.2% (95% CI, 2.9-5.5). The ROC curve analysis indicated that the NCAR cylinder test (cutoff value ≥ 0.875 D) was the best test for screening target conditions. With regard to age groups, UCVA ≤ 0.75 (Snellen equivalent) and ≤ 0.85 were the best referral criteria for ages ≤ 4 years and ≥ 5 years, respectively. Combining the UCVA test with the NCAR test (the child was referred after failing both tests) increased specificity without significantly decreasing sensitivity. CONCLUSIONS: The UCVA and NCAR tests performed by vision-screening technicians are adequately sensitive and specific for preschool vision screening. The ROC curve analysis was used for determining the appropriate screening criteria for these tests, and combining the tests increased their accuracy. The screening criteria should be age dependent. When analyzing the test accuracy in ophthalmic problems, if the disease of interest does not symmetrically (in terms of disease severity and prevalence) involve both eyes, the prevalence based on only 1 eye should be interpreted with caution.

Efforts to improve the surgical outcome for exotropia and investigation of the insertion locations of the extraocular muscles.

In our previous retrospective study, we found that using the strabismus surgery dosages established by western strabismus mentors tends to result in undercorrection of Taiwanese exotropia (XT) patients compared with those in western populations. We also discovered that the location of extraocular muscle (EOM) insertion could vary by ethnicity. In this study, using a generalized estimation equation model, we compared the XT surgery outcome between augmented and original strabismus surgery dosages in Taiwanese patients. We also conducted an observational study to investigate the horizontal EOM insertion location in a Taiwanese population and compared the data with Dr. Apt L.'s study. For Taiwanese XT patients, augmented surgical dosages resulted in significantly better outcome at 6 months and 1 year postoperatively compared with original surgical dosages (p = 0.003 and p < 0.001, respectively). The distance from the lateral recuts muscle (LR) insertion location to the limbus was significantly shorter in Taiwanese than in white Americans (6.5 vs. 6.9 mm, respectively, p = 0.0001). Furthermore, the medial rectus muscle and LR insertion locations differed significantly between males and females (p < 0.001 and p = 0.023, respectively). The patients' sex did not affect the surgery outcome. Augmented surgery doses modified from western strabismus mentors produce better surgery outcome for Taiwanese XT patients. Surgeons may require country-specific guidelines for strabismus surgery dosage. We also demonstrated a simple method for young ophthalmologists to establish their own normograms to improve their surgical success rate. Our study confirms that LR insertion locations differ between Taiwanese and White Americans.

Bidirectional associations between hyperopia, myopia, astigmatism, and strabismus, and attention-deficit/hyperactivity disorder in children: a national population-based cohort study.

OBJECTIVES: The present study analyzed the reciprocal relationships between four common pediatric ophthalmic diseases (i.e., hyperopia, myopia, astigmatism, and strabismus) and attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: This study enrolled 86,028 children with ADHD and 1,798,673 children without ADHD in the Taiwan Maternal and Child Health Database who were born at any time from 2004 to 2017. Cox proportional hazards regression models were used to estimate the bidirectional relationships of the four ophthalmic diseases with ADHD in children after adjusting for age, sex, and gestational age at birth. Survival curves for time-to-event variables were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the curves. RESULTS: The results indicated that ADHD significantly predicted the occurrence of hyperopia, myopia, astigmatism, and strabismus. Furthermore, hyperopia, myopia, astigmatism, and strabismus significantly predicted the occurrence of ADHD. The time between enrollment and ADHD diagnosis was shorter for patients with ophthalmic diseases than for the control group, and the time between enrollment and ophthalmic disease diagnosis was also shorter for ADHD patients than for the control group. Sex differences were found in the associations between ADHD and ophthalmic diseases. CONCLUSION: Clinicians should monitor children with ADHD for hyperopia, myopia, astigmatism, and strabismus to ensure appropriate treatment, and vice versa.

A comparative multicentric long-term study of un-augmented modified Nishida procedure vs augmentation in unilateral sixth nerve palsy.

PURPOSE: To compare the effectiveness of three procedures: modified Nishida procedure alone vs modified Nishida procedure combined with medial rectus recession (MRc) vs modified Nishida procedure combined with MRc and botulinum toxin (BT) for severe unilateral sixth nerve palsy. DESIGN: Consecutive, interventional case series. METHODS: The medical records of a consecutive series of patients with severe unilateral sixth nerve palsy who underwent modified Nishida procedure in multiple centres were reviewed. Surgical technique was decided preoperatively at the surgeon's discretion. The preoperative and postoperative findings were compared. RESULTS: Of the 43 patients with abducens palsy that received the procedure, 32 were included (mean age 38.6 ± 19.8 years). Mean preoperative deviation was 63.0 ± 27.3 prism dioptres (PD) and mean limitation of abduction -4.5 ± 1.2. Five patients underwent a modified Nishida procedure alone, 24 patients had an additional MRc and 3 patients were also injected with BT. Overall, the average correction of modified Nishida technique by itself was 29.4 ± 6.6 PD (range 20-36) and adding a MRc corrected 62.6 ± 23.8 PD (range 24-120). Modified Nishida procedure, MRc and BT altogether corrected 95.0 ± 18.0 PD (range 75-110). No postoperative complications were observed in any of the patients. CONCLUSIONS: Excellent outcomes with fewer complications are obtained with modified Nishida procedure alone. The need for additional procedures such as MRc and BT which increase the effect in primary position can be determined depending on passive duction and preoperative horizontal deviation.

Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo.

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

Effects of patient- and operation-related factors on postoperative pain after orthognathic surgery.

PURPOSE: This study aimed to assess the association between patient- and operation-related factors and postoperative pain in patients undergoing intraoral vertical ramus osteotomy (IVRO) or IVRO + genioplasty (GeP) for the treatment of mandibular prognathism. MATERIALS AND METHODS: A visual analog scale (VAS) was used to evaluate postoperative pain for 2 days in 63 patients who underwent orthognathic surgery (42 IVRO and 21 IVRO + GeP). Correlations between VAS and patient age, sex, blood loss, operation time, and intraoperative reduction in blood parameters were assessed and compared between IVRO and IVRO + GeP procedures. RESULTS: Mean operation time and blood loss were 252.02 minutes and 99.64 mL in the IVRO group and 317.62 minutes and 187.86 mL in the IVRO + GeP group, respectively. Operation time, blood loss, and postoperative reduction in blood parameters were significantly greater in the IVRO + GeP group than in the IVRO group. Mean VAS scores on the first and second postoperative days were 3.02 and 1.33 in the IVRO group and 2.95 and 1.14 in the IVRO + GeP group. However, postoperative pain did not differ significantly between the IVRO and IVRO + GeP groups on the first or second postoperative day. CONCLUSIONS: Postoperative pain associated with orthognathic surgery was acceptable, controllable, and not different between IVRO and IVRO + GeP procedures.

Baby oil therapy for uremic pruritus in haemodialysis patients.

AIMS: The purpose of this study was to investigate the effectiveness of chilled/un-chilled baby oil therapy for treating uremic pruritus in haemodialysis patients. BACKGROUND: Uremic pruritus affects 50-90% of haemodialysis patients, which makes it one of the most common medical problems in this population. Pruritus can cause skin infection, desquamation, pathological skin change, sleep disorder, anxiety, depression and social dysfunction. DESIGN: A prospective, pretest-post-test quasi-experimental design was used. METHODS: Haemodialysis patients with uremic pruritus were recruited and randomly assigned to one of three groups: experimental group 1 (chilled baby oil treatment; n = 30), experimental group 2 (un-chilled baby oil treatment; n = 31) and a control group (routine care only; n = 32). Participants in experimental group 1 and experimental group 2 were treated with chilled and un-chilled baby oil, respectively, for 15 minutes at least once daily for three weeks. The control group received no intervention other than standard care. Data collection included demographic data and itch severity. Medical records were also reviewed. RESULTS: The baseline characteristics of subjects in this study were as follows: 59% were male, mean age was 61·88 (SD 12·7) years, mean duration of haemodialysis was 5·31 years, mean duration of uremic pruritus was 40·58 (SD 37·8) months and mean intensity of uremic pruritus was mild. The anti-pruritic effects were significantly larger in subjects treated with either chilled or un-chilled baby oil than in those who received routine care. Anti-pruritic effects did not significantly differ between experimental group 1 and experimental group 2. CONCLUSIONS: The study confirmed that, for relieving pruritus in haemodialysis patients, either chilled or un-chilled baby oil is as effective as moisturising lotions and cooling soothing agents. RELEVANCE TO CLINICAL PRACTICE: Applying baby oil is a simple, safe, inexpensive and easily administered treatment for itchy skin in haemodialysis patients. By preventing or reducing uremic pruritus, baby oil treatment may also improve quality of life in this patient group.

Punicalagin Attenuates LPS-Induced Inflammation and ROS Production in Microglia by Inhibiting the MAPK/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation.

Purpose: Neurodegenerative diseases are associated with neuroinflammation along with activation of microglia and oxidative stress, but currently lack effective treatments. Punicalagin is a natural bio-sourced product that exhibits anti-inflammatory effects on several chronic diseases; however, the anti-inflammatory and anti-oxidative effects on microglia have not been well examined. This study aimed to investigate the effects of punicalagin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and the production of ROS using murine microglia BV2 cells. Methods: BV2 cells were pre-treated with punicalagin following LPS treatment to induce inflammation. The secretion of NO and PGE2 was analyzed by Griess reagent and ELISA respectively, while the expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were analyzed using Western blotting, the production of IL-6 was measured by ELISA, and the activity of NF-κB was detected using promoter reporter assay. To examine whether punicalagin affects NLRP3 inflammasome activation, BV2 cells were stimulated with LPS and then treated with ATP or nigericin. The secretion of IL-1ß was measured by ELISA. The expressions of NLRP3 inflammasome-related proteins and phospho IκBα/IκBα were analyzed using Western blotting. The production of intracellular and mitochondrial ROS was analyzed by flow cytometry. Results: Our results showed that punicalagin attenuated inflammation with reduction of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1ß, and reduction of IL-6 led to inhibition of STAT3 phosphorylation by LPS-induced BV2 cells. Punicalagin also suppressed the ERK, JNK, and p38 phosphorylation, attenuated NF-κB activity, inhibited the activation of the NLRP3 inflammasome, and reduced the production of intracellular and mitochondrial ROS by LPS-induced BV2 cells. Conclusion: Our results demonstrated that punicalagin attenuated LPS-induced inflammation through suppressing the expression of iNOS and COX-2, inhibited the activation of MAPK/NF-κB signaling pathway and NLRP3 inflammasome, and reduced the production of ROS in microglia, suggesting that punicalagin might have the potential in treating neurodegenerative diseases.