Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy / 中国药理学通报

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ‍-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

R-CHOP and consolidation radiotherapy for limited-stage and low-IPI high-grade b-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements: A single-center case series and review of literature

@#High-Grade B-Cell Lymphoma (HGBCL) with gene rearrangements in MYC and BCL2 and/or BCL6 is an aggressive malignancy usually presenting in advanced stages. Current recommendations suggest the use of regimens more intensive than R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), which are based on retrospective studies and single-arm prospective trials that included patients who are mostly in the advanced stage, and did not receive consolidation radiotherapy. The optimal approach and treatment of HGBCL, whether limited-stage (LS) or advanced-stage, remains to be determined. Here we describe the promising outcomes of three patients with LS and low IPI HGBCL with the use of R-CHOP as induction chemotherapy regimen, which was followed by consolidation radiotherapy. Three women, 54-, 60-, and 64-years of age diagnosed to have HGBCL with MYC, and BCL2 and/or BCL6 rearrangements, with Ann Arbor stages I-IIE were included in this case series. All three patients had complete metabolic response to 6 cycles of R-CHOP and was subsequently treated with consolidation involved site radiotherapy (ISRT; total dose 30-36 Gy). Chemotherapy and radiotherapy were tolerated very well. All patients remain to be in remission, with the longest being at 23 months. Outcomes of patients with HGBCL generally remain to be poor, but this may not be the case for patients with limited-stage disease and favorable clinicopathologic risk profile. Nevertheless, the treatment of HGBCL is currently evolving and more studies are needed to determine the ideal approach and preferred chemotherapy regimen. Also, more studies are needed to elucidate the potential role of consolidation radiotherapy in patients with limited-stage HGBCL to improve survival outcomes. Findings of this case series suggest that patients with LS HGBCL may still derive benefit from R-CHOP followed by consolidation ISRT, but prospective trials are needed to confirm this.

Modified Liuwei Dihuangtang Combined with Losartan Potassium Regulates ACE1/AngⅡ/AT1R Axis and Intestinal Flora in Rat Model of Diabetic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.

Mechanism of Yishen Tongluo Prescription in Inhibiting Endoplasmic Reticulum Stress and Improving Apoptosis of Renal Tubular Epithelial Cells Based on PERK/ATF4/CHOP / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yishen Tongluo prescription （YSTLP） on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4）/transcription factor C/EBP homologous protein （CHOP）. MethodThe db/db mice were randomly divided into model group， valsartan group （10 mg·kg-1）， and low， middle， high-dose YSTLP groups （1， 2.5， 5 g·kg-1）. Samples were collected after eight weeks of drug intervention. In addition， db/m mice in the same litter served as the control group. Human renal tubular epithelial cells （HK-2） were cultured in vitro and divided into the control group， advanced glycated end-product （AGE） group， and AGE + low， middle， and high-dose YSTLP groups （100， 200， 400 mg·L-1）. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element （UPRE） and endoplasmic reticulum stress. Immunohistochemical （IHC） analysis was carried out to measure the protein expressions of phosphorylated PKR （p-PERK）， CHOP， and ATF4. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 （XBP1） in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK， PERK， CHOP， ATF4， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay， HK-2 cell viability was significantly reduced， and the apoptosis rate was elevated in the AGE group compared with the control group （P<0.01）. The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced （P<0.01）， and those of Bax were significantly increased （P<0.01）. The protein expression level of cleaved Caspase-3 was significantly increased （P<0.01）. Compared with the AGE group， YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate （P<0.01）. The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner （P<0.01）， and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner （P<0.01）. The intracellular Ca2+ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group （P<0.01）. The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased （P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the AGE group， YSTLP effectively improved intracellular Ca2+ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner （P<0.01）. It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 （P<0.01） and the protein expression levels of intracellular p-PERK， CHOP， and ATF4 in a dose- and time-dependent manner （P<0.01）. In animal experiments， the protein expression level of Bcl-2 was significantly reduced（P<0.01）， and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group （P<0.05）. The protein expression level of Bcl-2 was dose-dependently elevated， and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group （P<0.01）. Compared with the control group， the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group （P<0.05， P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the model group， YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 （P<0.01） and the protein expression levels of p-PERK， CHOP， and ATF4 （P<0.01）. ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells， and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway.

PCorteSoft - Sistema para la determinación del punto de corte óptimo en escalas predictivas y la categorización de variables continuas

Al desarrollar modelos de predicción para su aplicación en la práctica clínica, los profesionales de la salud suelen categorizar las variables clínicas que son de naturaleza continua. En muchas ocasiones estos modelos constituyen la base para la confección de escalas predictivas, a partir de las cuales se estratifica a los pacientes en varias categorías atendiendo al fenómeno estudiado. En estos casos se requiere la determinación de uno o varios puntos de cortes que permitan dividir el recorrido de la variable, variables continuas o puntuaciones de una escala, en dos o más categorías. El presente trabajo tiene como objetivo la automatización de diferentes métodos para dicotomizar variables continuas en modelos de predicción clínica, donde la variable respuesta es dicotómica, y determinar el punto de corte óptimo en la estratificación de pacientes en dos categorías, a partir de escalas de predicción. Para ello se elaboró un software en el lenguaje de programación R, que implementa diferentes métodos para la determinación del punto de corte óptimo, lo cual agiliza el trabajo investigativo de los especialistas de salud en el proceso de elaboración de modelos predictivos y/o escalas de predicción.

When developing predictive models for application in clinical practice, health professionals often categorize clinical variables that are continuous in nature. In many cases, these models are the basis for the development of predictive scales from which patients are stratified into various categories according to the phenomenon under study. In both cases, it is necessary to determine one or more cut-off points that allow dividing the path of the variable, continuous variables, or scores of a scale into two or more categories. The aim of the present work is to automate different existing methods for dichotomizing continuous variables in clinical prediction models where the response variable is dichotomous, as well as to determine the optimal cut-off point for stratifying patients into two categories, based on prediction scales. For this purpose, a software was developed in the R programming language, which implements different existing methods for the determination of the optimal cut-off point, speeding up the research work of health specialists in the process of developing predictive models and/or prediction scales.

The Localization of R-Spondin1 and R-Spondin 3 Peptides in Rat Hypothalamus: An Immunohistochemical Study / Localización de los Péptidos R-Spondin1 y R-Spondin3 en el Hipotálamo de Rata: Un Estudio Inmunohistoquímico

SUMMARY: The R-spondin protein family is a group of proteins that enhance Wnt/b-catenin signaling and have pleiotropic functions in stem cell growth and development. In the literature reviews, there is no histomorphological study showing the localization and distribution of R-spondins in different hypothalamic nuclei. For this reason, the purpose of this study was to determine the localization, distribution characteristics, and densities in the hypothalamic nuclei of neurons expressing Rspo1 and Rspo3 proteins. The free-floating brain sections of the male rats who were not exposed to any treatment were stained with the indirect immunoperoxidase method using the relevant antibodies. As a result of the immunohistochemical studies, it was determined that neurons expressing the Rspo1 protein were found in large numbers in the supraoptic nucleus (SON), the suprachiasmatic nucleus (SCh), anterior paraventricular nucleus, periventricular hypothalamic nucleus (PeV), anterior hypothalamic area, magnocellular preoptic nucleus (MCPO) and the lateral hypothalamic area (LH) from the hypothalamic nuclei, while they were localized in fewer numbers in the arcuate nucleus (ARC). Rspo3 protein expression was found in neurons localized in the hypothalamic nuclei SON, paraventricular nucleus (PVN), PeV, ARC, ventromedial nucleus (VMH), LH, anterior parvicellular nucleus, and zona inserta (ZI). In addition, neurons synthesizing both peptides were found in the cortex and hippocampus regions (H). Rspo1 and 3 proteins are expressed in hypothalamic energy homeostatic areas, thus these proteins may be involved in the regulation of food intake.

La familia de proteínas R-espondina es un grupo de proteínas que mejoran la señalización de Wnt/b-catenina y tienen funciones pleiotrópicas en el crecimiento y desarrollo de las células madre. En las revisiones de la literatura no existen estudios histomorfológicos que muestren la localización y distribución de las R-espondinas en diferentes núcleos hipotalámicos. Por esta razón, el propósito de este estudio fue determinar la localización, características de distribución y densidades en los núcleos hipotalámicos de neuronas que expresan las proteínas Rspo1 y Rspo3. Secciones de cerebro flotantes de ratas macho que no fueron expuestas a ningún tratamiento se tiñeron con el método de inmunoperoxidasa indirecta utilizando los anticuerpos pertinentes. Como resultado de los estudios inmunohistoquímicos, se determinó que las neuronas que expresan la proteína Rspo1 se encontraron en gran número en el núcleo supraóptico (SON), el núcleo supraquiasmático (SCh), el núcleo paraventricular anterior, el núcleo hipotalámico periventricular (PeV), el núcleo hipotalámico anterior área, núcleo preóptico magnocelular (MCPO) y el área hipotalámica lateral (LH) de los núcleos hipotalámicos, mientras que se localizaron en menor número en el núcleo arqueado (ARC). La expresión de la proteína Rspo3 se encontró en neuronas localizadas en los núcleos hipotalámicos SON, núcleo paraventricular (PVN), PeV, ARC, núcleo ventromedial (VMH), LH, núcleo parvicelular anterior y zona inserta (ZI). Además, se encontraron neuronas que sintetizan ambos péptidos en las regiones de la corteza y el hipocampo (H). Las proteínas Rspo1 y 3 se expresan en áreas homeostáticas de energía hipotalámicas, por lo que estas proteínas pueden estar involucradas en la regulación de la ingesta de alimentos.

Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system棓Bharat Protocol� (Pilot study)

Purpose: Outcome of topography?guided excimer laser ablation in conjunction with accelerated, high?fluence cross?linking in corneal ecstatic disease using the NIDEK CXIII equipped with CATz algorithm from the FinalFit software棓Bharat Protocol.� Methods: Retrospective case record review of 30 eyes of 17 patients of stage 1?3 keratoconus who underwent the procedure was performed. Data collected were for visual acuity, distortion?induced eye pain, and keratometry. Pachymetry, lower order and higher order aberrations, spherical aberrations, and topographic cylinder were documented from by Scheimpflug imaging (Pentacam 70700: Oculus, Wetzlar, Germany). Results: At a minimum follow?up of 6 months (range 6.2� months), there was significant improvement in UCVA (P < 0.00001), BCVA (P = 0.0061), decrease in Kmax (P = 0.0349), Ksteep (P < 0.0411), Kflat (P = 0.0099), and pachymetry (P = 0.0001). Significant improvement was also seen in distortion?induced eye pain (27/30 to 2/30; P < 0.00001). A more than two?line improvement in UCVA and BCVA was seen in 23/30 and 17/30 cases, respectively. Ectasia was stabilized in all cases at the last follow?up, and no complications were seen. Conclusions: The 揃harat� Protocol to arrest keratectasia progression and improve corneal regularity is a safe and efficacious alternative as a keratoconus management option. This is the first such study on Nidek Platform for the same.

The Predictive Value of R Wave Peak Time to Detect Thrombus Burden in St-segment Elevation Myocardial Infarction: A Retrospective Cohort Study in a Tertiary Medical Center

Abstract Background: Patients with higher thrombus burden have higher procedural complications and more long-term adverse cardiac events. Detecting patients with high thrombus burden (HTB) before coronary intervention could help avoid procedural complications. Objective: The research aimed to analyze the R wave peak time (RWPT) on the electrocardiogram to predict thrombus burden before coronary angiography in patients with acute ST-segment elevation myocardial infarction (STEMI). Materials and Methods: A total of 159 patients with STEMI were included in the study conducted at a tertiary medical center. The thrombolysis in myocardial infarction (TIMI) thrombus scale was applied to assess the thrombus burden. TIMI thrombus grades 0, 1, 2, and 3 were accepted as low; 4 and 5 had HTB. RWPT was measured from the beginning of the QRS complex to the R-peak from the leads pointing to the infarct-related artery. Results: Patients were divided into two groups according to their angiographically defined thrombus burden as low and high. The low thrombus burden group (LTB) comprised fifty-four patients, whereas the HTB group comprised 105 patients. In the LTB group, RWPT was 47.96 ± 9.17 ms, and in the HTB group was 53.58 ± 8.92 ms; it was significantly longer (p < 0.01). Receiver operating characteristic analysis showed that a cut-off value of preprocedural RWPT of > 46.5 ms predicted the occurrence of HTB with a sensitivity and specificity of 87.62% and 51.85%, respectively (AUC 0.682, 95% CI 0.590-0.774, p < 0.001). Conclusion: The present study evaluated the relationship between the RWPT and thrombus burden in STEMI patients. Based on the results, RWPT is an independent predictor of HTB.

Traducción, validación, y adaptación del español al Kreyol-creole haitiano de la Escala de Depresión del Centro de Estudios Epidemiológicos (CESD-R-20)

Introducción. A pesar de la importante presencia de la población haitiana en países de América Latina, existen pocos estudios que evalúen la salud mental en esta población; una de las razones es la falta de instrumentos psicométricos en kreyol (creole haitiano). Objetivo. Adaptar la versión en español de la Escala de Depresión del Centro de Estudios Epidemiológicos (CESD-R-20) al kreyol. Métodos. Estudio transversal de muestreo bietápico con 207 migrantes haitianos viviendo en Santiago de Chile, se tradujo y retrotradujo la Escala CESD-R-20 del español al kreyol. Resultados. 132 participantes respondieron la encuesta en kreyol y 75 en español. Las técnicas de detección de la dimensionalidad recomiendan retener un único componente y tres factores, con pocas excepciones a través de las muestras. Las soluciones factoriales llevan a retener un único factor, que presenta un Alfa de Cronbach =0.92 (IC: 0.90-0.94) adecuado. Estos resultados indican que se necesita un único factor. Discusión y conclusión. La adaptación del instrumento CESD-R-20 de español al kreyol obtiene evidencias de validez favorables y puede servir para iniciar nuevos estudios en población migrante haitiana en su trayecto por América Latina, si bien es necesario seguir ampliando el proceso de validación.

Introduction. Although the Haitian migrant population has a significant presence in Latin American countries, a few studies assess this population's mental health; one of the reasons is the lack of psychometric instruments in kreyol (Haitian Creole). Objective. Adapt the Spanish version of the Depression Scale of the Center for Epidemiological Studies (CESD-R-20) into kreyol. Methods. Based on a cross-sectional two-stage cluster sampling with 207 Haitian migrants living in Santiago de Chile, we conducted translation and back translation of the CESD-R-20 Scale from Spanish to kreyol; additionally, we reached an adapted version in Spanish. Results. In total, 132 participants answered the survey in Kreyol and 75 in Spanish. Dimensionality detection techniques recommend retaining a single component and three factors, with few exceptions across samples. Exploration of factor solutions leads to the retention of a single factor, which has an adequate Cronbach's alpha=0.92 (IC: 0.90;0.94). These results indicate that only one factor is needed. Discussion and conclusion. The adaptation of the Spanish CESD-R-20 instrument to Kreyol has obtained favorable validity evidence and can be used to initiate new studies on the Haitian migrant population on their journey through Latin America, although the validation process needs to be further extended.

Pain and Physiological Stress During Minimally Invasive Surfactant Therapy (MIST) in Very Preterm Infants

Objectives: To evaluate the pain or physiological stress caused during minimally invasive surfactant therapy (MIST) to very preterm neonates. Methods: In this prospective observational study conducted in a tertiary NICU, very preterm neonates were assessed for pain using Premature Infant Pain Profile-Revised (PIPP-R) score before, during and after MIST. Changes in the heart rate and oxygen saturation were also recorded during the procedure. Results: 23 neonates who received MIST were assessed for pain using PIPP-R. Mean (SD) PIPP-R score during MIST was 3.87(1.3), before; 12.83 (1.9), during; and 6.26 (1.0), after the procedure, respectively (all P<0.001). Heart rate and oxygen saturation were also significantly reduced during MIST (P<0.001). Conclusion: The high PIPP-R scores during surfactant administration suggest that MIST can cause moderate to severe pain/discomfort and significant physiological stress in very preterm infants.

Reducción, reutilización y reciclaje: Una revisión crítica del conocimiento científico sobre las pérdidas y desperdicios de alimentos en Chile

Reducir, reutilizar y reciclar, "regla de las tres R", son estrategias que promueven una actitud responsable hacia el medioambiente y contribuyen al desarrollo sostenible. El objetivo de esta revisión fue analizar las publicaciones científicas generadas en Chile en el área de las pérdidas y desperdicios de alimentos (PDA), con enfoque en su cuantificación y basadas en "la regla de las tres R". Se realizó una búsqueda de literatura en tres bases de datos: Web of Science, Pubmed y Scopus. Los artículos originales seleccionados se clasificaron según tipo de acción, etapa de la cadena de suministro de alimentos, grupo de alimentos, cuantificación de PDA y tipo de estrategia (reducción, reutilización o reciclaje). Se encontraron 5 artículos de revisión y 31 artículos originales. La revalorización de subproductos agroindustriales fue la principal acción involucrada en los estudios de PDA (n= 22). El tipo de subproducto también fue analizado, y se encontró que los compuestos fenólicos provenientes de frutales son los más estudiados. Solo el 32% (12/31) de los artículos reportaron información sobre cuantificación de PDA. La revalorización de subproductos sumada a la recuperación de alimentos para producción de energía (n= 4) y de compostaje (n= 2) hacen que el reciclaje sea la estrategia más investigada. Estos antecedentes evidencian la necesidad de complementar la investigación nacional a nivel de acciones que apunten más hacia la reducción y reutilización de PDA y su cuantificación. Este conocimiento permitirá establecer líneas base y planes de monitoreo que contribuyan al cumplimiento de los Objetivos de Desarrollo Sostenible en Chile.

Reduce, reuse, and recycle "the 3Rs rule" are strategies that promote a responsible attitude towards the environment and contribute to sustainable development. The objective of this review was to analyze the scientific publications generated in Chile in the area of food loss and waste (FLW), with a focus on its quantification and based on "the 3Rs rule". A literature search was carried out in three databases: Web of Science, Pubmed, and Scopus. The selected original articles were classified according to the type of action, stage of the food supply chain, food group, FLW quantification, and type of strategy (reduction, reuse, or recycling). Five review articles and 31 original articles were found. The revalorization of agro-industrial by-products was the main initiative involved in the FLW studies (n= 22). The type of by-product was also analyzed, and it was found that the phenolic compounds from fruits are the most studied. Only 32% (12/31) of the articles reported information on FLW quantification. The revalorization of by-products added to food recovery for energy production (n= 4) and composting (n= 2) make recycling the most researched strategy. These antecedents show the need to complement the national research at the level of actions that point more towards reducing and reusing of FLW and its quantification. This knowledge will allow the establishment of baselines and monitoring plans that contribute to the fulfillment of the Sustainable Development Goals in Chile.

Reemplazar ideas, reducir equívocos y refinar argumentos: una reinterpretación de las 3R de la experimentación animal

Propósito/Contexto. En el presente trabajo se llevará a cabo una reinterpretación de las tres erres (3R) propuestas por William Russell y Rex Burch (reemplazo, reducción y refinamiento), con el objetivo de ampliar su alcance y mejorar las prácticas de experimentación con animales no humanos. Metodología/Enfoque. Se revisará el sentido que le dieron Russell y Burch a las 3R y se evaluará el modo en que cada una de ellas podría redefinirse o complementarse a la luz de las prácticas científicas, las posibilidades técnicas y los conocimientos bioéticos actuales vinculados al uso de animales en investigación. Resultados/Hallazgos. El artículo mostrará que 1) no solo habrían de reemplazarse animales, sino también las ideas equívocas que tenemos, tanto sobre ellos, como sobre la importancia de la educación bioética en la formación científica, 2) que la reducción, además de referirse al número de sujetos utilizados en cada experimento, debería servir para acabar con investigaciones innecesarias, repetitivas y superfluas, así como con algunos persistentes equívocos sobre el modo de operar de la ciencia y 3) que el refinamiento tendría que salir del espacio experimental para extenderse al modo en que pensamos sobre ética animal en el ámbito de la investigación. Discusión/Conclusiones/Contribuciones. El trabajo da cuenta de la importancia que tiene la incorporación del conocimiento bioético contemporáneo en las prácticas de experimentación con animales para mejorar el carácter reflexivo y ético de la ciencia.

Purpose/Background. In the present work, a reinterpretation of the 3Rs (3Rs) proposed by William Russell and Rex Burch (Replacement, Reduction and Refinement) will be carried out with the aim of broadening its scope and improving nonhuman animal experimentation practices. Methodology/Approach. The meaning given by Russell and Burch to the 3Rs will be reviewed and the way in which each of them could be redefined or complemented in the light of current scientific practices, technical possibilities and bioethical knowledge related to the use of animals in research will be evaluated. Results/Findings. The article will show that 1) not only animals should be replaced, but also the misconceptions we have, both about them and about the importance of bioethics education in scientific training, 2) that the reduction, in addition to the number of subjects used in each experiment, should serve to end unnecessary, repetitive and superfluous research, as well as some persistent misconceptions about the way science operates, and 3) that refinement should go beyond the experimental space to extend to the way we think about animal ethics in the research setting. Discussion/Conclusions/Contributions. The paper reports on the importance of incorporating contemporary bioethical knowledge into animal experimentation practices to enhance the reflexive and ethical character of science.

Objetivo/Contexto. Neste documento, uma reinterpretação dos 3Rs (3Rs) propostos por William Russell e Rex Burch (Substituição, Redução e Refinamento) será realizada com o objetivo de ampliar seu escopo e melhorar as práticas não-humanas de testes em animais. Metodologia/ Abordagem. Revisaremos o significado dado por Russell e Burch aos 3Rs e avaliaremos como cada um deles poderia ser redefinido ou complementado à luz das práticas científicas atuais, possibilidades técnicas e conhecimentos bioéticos relacionados ao uso de animais na pesquisa. Resultados/Descobertas. O artigo mostrará que 1) não somente os animais devem ser substituídos, mas também conceitos errôneos sobre eles e a importância da educação bioética no treinamento científico, 2) que a redução, além do número de sujeitos utilizados em cada experimento, deve servir para eliminar pesquisas desnecessárias, repetitivas e supérfluas, assim como alguns conceitos errôneos persistentes sobre a maneira como a ciência funciona, e 3) que o refinamento deve se estender além do espaço experimental para a maneira como pensamos sobre a ética animal na pesquisa. Discussão/Conclusões/Contribuições. O artigo explica a importância de incorporar o conhecimento bioético contemporâneo nas práticas de experimentação animal para realçar o caráter reflexivo e ético da ciência.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

PREVELANCE OF CARBAPENEMASE PRODUCING ORGANISMS AND MOLECULAR RAPID DETECTION OF DIFFERENT GENES FROM VARIOUS CLINICAL ISOLATES IN PATIENTS ADMITTED AT TERTIARY CARE HOSPITALS OF VADODARA

Introduction- Carbapenemase-producing organisms (CPO) have been identied as an urgent healthcare threat. The spread of carbapenemase-producing Enterobacterales (CPE) is a global health problem of great concern. Rapid detection of carbapenemase-producing organisms is clinically desirable for hospital infection control and antibiotic stewardship. Recently, an on-demand polymerase chain reaction (PCR) assay, namely, the Xpert Carba- R assay, that requires less than an hour of turnaround time, had been developed for CPO detection in clinical samples to identify and guide infection control programs to contain the spread of CPO within a hospital. Carba-R assay is a Objective- qualitative multiplex real-time PCR method that qualitatively detects and differentiates ve common carbapenemase genes (blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP) directly from clinical samples or puried colonies within approximately 1 hour. This benets hospitals and patients by facilitating timely Infection Prevention & Control measures, thereby reducing risk of exposure, transmission and bed-days lost. In this study, the Xpert Carba-R assay was evaluated for Materials & Methods- detection of the ve carbapenemase genes (blaKPC, blaNDM, blaIMP, blaOXA-48, and blaVIM) in total of 40 non duplicate various clinical samples of admitted patients in tertiary care hospitals of Vadodara. We performed Carba-R on 40Result- isolates: 18 blood samples, 06 urine, 05 rectal swabs, 03 Endotracheal secretion, 03 Pus, 02 wound discharge, 01 Bronchoalveolar lavage uid, 01 sputum, and 01 ERCP stent isolates. 36/40 (90%) isolates had one or more carbapenemase genes. They were as follows: 19/40 (47.5%) both OXA48 and NDM , 12/40 (30%) NDM and 05/40(12.5%) OXA-48. There were 04/40 (10 %) isolates which were Carbapenem resistant on disc diffusion & VITEK but none of the resistant genes were detected possibly due to other resistant mechanism like efux pump and porin channels. Klebsiella pneumoniae was the most common isolate with CR, 34/40 (85%). The most frequent genes encountered in Klebsiella pneumoniae were both OXA48 and NDM, 19/34 (55.88%), NDM 08/34 (23.53%) followed by OXA 48, 05/34 (14.71%) and Out of 34 Klebsiella isolates, 02 isolates failed to detect any of these ve carbapenemase genes. Xpert Carba-R assay provides good reliable results for detection and Conclusion- differentiation of ve carbapenemase genes in clinical isolates. Compared to bacterial culture followed by PCR identication of resistance genes from colonies, the Carba-R assay reduced turnaround time from 48 to 72 hours to less than 1 hour. Carbapenemase genes were detected by the Carba-R assay in Klebsiella pneumoniae (34/40), Escherichia coli (5/40), Acinetobacter spp (1/40). The Carba-R assay detected 19 both OXA48 and NDM (47.5%), 12 blaNDM (30% and 05 blaOXA-48 (12.5%) genes. Laboratory detection of these genes may help improve patient outcomes by tailoring therapy. This study was conducted for understanding the molecular epidemiology of Carbapenemase producing Enterobacteriaceae in a tertiary care hospital. The combined use of the Xpert Carba-R assay and culture produces rapid and reliable results for the active surveillance of CPO in patients

Deadly ECG Sign: An Aspect to Recognize in the Settings of STEMI

Learning Objectives: Learn how to identify and differentiate the shark fin EKG pattern from other EKG patterns and abnormalities. Explore the potential diagnostic and prognostic implications of the shark fin EKG pattern, including its association with increased risk of arrhythmias and sudden cardiac death. Background: The Lambda-wave ECG, also known as the Shark fin or Thombostone pattern, has been linked to ST-elevation myocardial infarction's (STEMI) hazardous implications. It is characterized by merged QRS, ST, and T waves, forming a 'triangular QRS-ST-T waveform' or 'giant R waves.' This treacherous signature poses an alarming risk, with chances of cardiogenic shock and ventricular fibrillation leading to fatality. To tackle this peril, implementing swift thrombolysis or percutaneous intervention for reperfusion is critical for successful treatment. For optimal outcomes, the preferred setting to utilize ventricular assist devices is the ICU. Misdiagnosis can happen and be seen as either wide complex tachycardia or ECG changes induced by hyperkalemia. Imperative to prevent severe complications, early detection and treatment are crucial. We are reporting three cases of this Ekg pattern.

Chemical and microbiological properties of Lake Aygir in Turkey and usage of drinking, fisheries, and irrigation / Propriedades químicas e microbiológicas do lago Aygir na Turquia e uso de bebidas, pescarias e irrigação

Abstract Since water is one of the essentials for life, the presence and quality of water in the habitat is extremely important. Therefore, water quality change and management of Lake Aygır was investigated in this study. For this, water samples collected from the lake and the irrigation pool between May 2015 and May 2016 were analyzed monthly. Spectrophotometric, titrimetric and microbiological methods were used to determine the water quality. According to some water quality regulations, HCO3, NH4, Cu, Mo, Br, fecal coliform and total suspended solid (TSS) values were found above the limit values. The other 29 parameters comply with Turkish national and international legislations. Lake Aygır was negatively affected by the surrounding settlements and agricultural activities. It is thought that the water resource should be monitored periodically and remedial studies should be done to prevent parameters exceeding the limits. However, Lake Aygır was generally suitable for drinking, use, fishing and irrigation.

Resumo Como a água é um dos elementos essenciais para a vida, a presença e a qualidade da água no habitat são extremamente importantes. Portanto, a mudança da qualidade da água e a gestão do lago Aygır foram investigadas neste estudo. Para isso, amostras de água coletadas no lago e na piscina de irrigação entre maio de 2015 e maio de 2016 foram analisadas mensalmente. Métodos espectrofotométricos, titulométricos e microbiológicos foram usados para determinar a qualidade da água. De acordo com alguns regulamentos de qualidade da água, os valores de HCO3, NH4, Cu, Mo, Br, coliformes fecais e total sólido suspenso (TSS) foram encontrados acima dos valores limite. Os outros 29 parâmetros estão em conformidade com as legislações nacionais e internacionais turcas. O lago Aygır foi afetado negativamente pelos assentamentos e atividades agrícolas ao redor. Pensa-se que o recurso hídrico deve ser monitorado periodicamente e estudos corretivos devem ser feitos para evitar que os parâmetros ultrapassem os limites. No entanto, o lago Aygır era geralmente adequado para beber, usar, pescar e irrigar.

Chemical and microbiological properties of Lake Aygir in Turkey and usage of drinking, fisheries, and irrigation / Propriedades químicas e microbiológicas do lago Aygir na Turquia e uso de bebidas, pescarias e irrigação

Since water is one of the essentials for life, the presence and quality of water in the habitat is extremely important. Therefore, water quality change and management of Lake Aygır was investigated in this study. For this, water samples collected from the lake and the irrigation pool between May 2015 and May 2016 were analyzed monthly. Spectrophotometric, titrimetric and microbiological methods were used to determine the water quality. According to some water quality regulations, HCO3, NH4, Cu, Mo, Br, fecal coliform and total suspended solid (TSS) values were found above the limit values. The other 29 parameters comply with Turkish national and international legislations. Lake Aygır was negatively affected by the surrounding settlements and agricultural activities. It is thought that the water resource should be monitored periodically and remedial studies should be done to prevent parameters exceeding the limits. However, Lake Aygır was generally suitable for drinking, use, fishing and irrigation.

Como a água é um dos elementos essenciais para a vida, a presença e a qualidade da água no habitat são extremamente importantes. Portanto, a mudança da qualidade da água e a gestão do lago Aygır foram investigadas neste estudo. Para isso, amostras de água coletadas no lago e na piscina de irrigação entre maio de 2015 e maio de 2016 foram analisadas mensalmente. Métodos espectrofotométricos, titulométricos e microbiológicos foram usados para determinar a qualidade da água. De acordo com alguns regulamentos de qualidade da água, os valores de HCO3, NH4, Cu, Mo, Br, coliformes fecais e total sólido suspenso (TSS) foram encontrados acima dos valores limite. Os outros 29 parâmetros estão em conformidade com as legislações nacionais e internacionais turcas. O lago Aygır foi afetado negativamente pelos assentamentos e atividades agrícolas ao redor. Pensa-se que o recurso hídrico deve ser monitorado periodicamente e estudos corretivos devem ser feitos para evitar que os parâmetros ultrapassem os limites. No entanto, o lago Aygır era geralmente adequado para beber, usar, pescar e irrigar.

In vitro evaluation for estrogenic mechanisms of the disinfectant benzalkonium chloride as an emerging contaminant

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.