2/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders. This study clarified that fraction 1 enriched phenolic compounds could attenuate ethanol-induced liver injury in BRL-3A cells via activating AMPK/p62/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders.Long-term care facilities (LTCFs), retirement homes (RHs), and other congregate care settings in Canada and worldwide have experienced significant COVID-19 outbreaks. As a health system response, our acute care hospital in Toronto, Ontario, Canada, developed and mobilized an onsite Infection Prevention and Control (IPAC) SWAT team (IPAC-SWAT) to regional settings on outbreak and implemented a strategy of support through education, training, and engagement. Between April 28, 2020, and June 30, 2020, IPAC-SWAT assessed 7 LTCFs and 10 RHs for IPAC preparedness and actively managed 10 of 13 COVID-19 outbreaks (LTCF n=5; RH n=5). IPAC-SWAT strategies were multi-interventional and intended to mitigate further viral transmission or prevent outbreaks. Dedicated training of local "IPAC champions" was facilitated at 7 sites (LTCF = 5; RH = 2) using a "train-the-trainer" approach to promote local knowledge, autonomy, and site-led audits and feedback.Mammalian genomes contain long domains with distinct average compositions of A/T versus G/C base pairs. In a screen for proteins that might interpret base composition by binding to AT-rich motifs, we identified the stem cell factor SALL4, which contains multiple zinc fingers. Mutation of the domain responsible for AT binding drastically reduced SALL4 genome occupancy and prematurely upregulated genes in proportion to their AT content. Inactivation of this single AT-binding zinc-finger cluster mimicked defects seen in Sall4 null cells, including precocious differentiation of embryonic stem cells (ESCs) and embryonic lethality in mice. In contrast, deletion of two other zinc-finger clusters was phenotypically neutral. Our data indicate that loss of pluripotency is triggered by downregulation of SALL4, leading to de-repression of a set of AT-rich genes that promotes neuronal differentiation. We conclude that base composition is not merely a passive byproduct of genome evolution and constitutes a signal that aids control of cell fate.Many sexual victimization survivors disclose their experience; however, there is limited research investigating why women disclose this experience and how reasons relate to psychopathology. The current online study aims to further understand the experiences of 142 female survivors (aged 18-29 years) by identifying their reason for disclosure and investigating how reasons relate to self-reported depression and post-traumatic stress disorder (PTSD) symptomology. Qualitative analyses identified two reasons intentional and elicited disclosures. Hierarchical linear regressions revealed that elicited disclosures were associated with higher PTSD symptomology than intentional disclosures above and beyond relevant covariates, suggesting that disclosure reason is an important factor in the recovery process.Extreme weather and climate events, such as heat waves, cyclones, and floods, are an expression of climate variability. These events and events influenced by climate change, such as wildfires, continue to cause significant human morbidity and mortality and adversely affect mental health and well-being. Although adverse health impacts from extreme events declined over the past few decades, climate change and more people moving into harm's way could alter this trend. https://www.selleckchem.com/products/bapta-am.html Long-term changes to Earth's energy balance are increasing the frequency and intensity of many extreme events and the probability of compound events, with trends projected to accelerate under certain greenhouse gas emissions scenarios. While most of these events cannot be completely avoided, many of the health risks could be prevented through building climate-resilient health systems with improved risk reduction, preparation, response, and recovery. Conducting vulnerability and adaptation assessments and developing health system adaptation plans can identify priority actions to effectively reduce risks, such as disaster risk management and more resilient infrastructure. The risks are urgent, so action is needed now.Gender microaggressions are everyday slights, insults, and invalidations theorized to create and sustain environments in which sexual harassment and assault of women is normative and permissible. Establishing a gender microaggressions taxonomy for undergraduate women may support efforts to improve campus climate and reduce sexual violence. This study aims to identify a gender microaggressions taxonomy for undergraduate women on college campuses. Five qualitative semi-structured focus groups (N = 23) were conducted with 18- to 25-year-old undergraduate women. Purposive sampling was employed and directed content analysis was performed. Seven themes emerged invisibility, intersectionality, caretaker and nurturer, women-dominated occupations, presumed incompetence, sexual objectification, and environmental invalidations.Introduction Cerebrovascular diseases encompass various disorders of the brain vasculature, such as ischemic/hemorrhagic strokes, aneurysms, and vascular malformations, also affecting the central nervous system leading to a large variety of transient or permanent neurological disorders. They represent major causes of mortality and long-term disability worldwide, and some of them can be inherited, including Cerebral Cavernous Malformation (CCM), an autosomal dominant cerebrovascular disease linked to mutations in CCM1/KRIT1, CCM2, or CCM3/PDCD10 genes.Areas covered Besides marked clinical and etiological heterogeneity, some commonalities are emerging among distinct cerebrovascular diseases, including key pathogenetic roles of oxidative stress and inflammation, which are increasingly recognized as major disease hallmarks and therapeutic targets. This review provides a comprehensive overview of the different clinical features and common pathogenetic determinants of cerebrovascular diseases, highlighting major challenges, including the pressing need for new diagnostic and therapeutic strategies, and focusing on emerging innovative features and promising benefits of nanomedicine strategies for early detection and targeted treatment of such diseases.

Moreover, we have constructed a phylogenetic tree for the novel coronavirus (COVID-19) and related coronaviruses by ENJ, which shows that COVID-19 and SARS-CoV are closer than other coronaviruses. Because it differs from the existing phylogenetic trees for those coronaviruses, we constructed a phylogenetic network for them. The network shows those species have had a reticulate evolution.Uncovering additional long non-coding RNA (lncRNA)-disease associations has become increasingly important for developing treatments for complex human diseases. Identification of lncRNA biomarkers and lncRNA-disease associations is central to diagnoses and treatment. However, traditional experimental methods are expensive and time-consuming. Enormous amounts of data present in public biological databases are available for computational methods used to predict lncRNA-disease associations. In this study, we propose a novel computational method to predict lncRNA-disease associations. More specifically, a heterogeneous network is first constructed by integrating the associations among microRNA (miRNA), lncRNA, protein, drug, and disease, Second, high-order proximity preserved embedding (HOPE) was used to embed nodes into a network. Finally, the rotation forest classifier was adopted to train the prediction model. In the 5-fold cross-validation experiment, the area under the curve (AUC) of our method achieved 0.8328 ± 0.0236. We compare it with the other four classifiers, in which the proposed method remarkably outperformed other comparison methods. Otherwise, we constructed three case studies for three excess death rate cancers, respectively. The results show that 9 (lung cancer, gastric cancer, and hepatocellular carcinomas) out of the top 15 predicted disease-related lncRNAs were confirmed by our method. In conclusion, our method could predict the unknown lncRNA-disease associations effectively.Mitochondrial dysfunction is a metabolic hallmark of cancer cells. In search of molecular factors involved in this dysregulation in hepatocellular carcinoma (HCC), we found that the nuclear-encoded long noncoding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was aberrantly enriched in the mitochondria of hepatoma cells. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we showed that MALAT1 interacted with multiple loci on mitochondrial DNA (mtDNA), including D-loop, COX2, ND3, and CYTB genes. MALAT1 knockdown induced alterations in the CpG methylation of mtDNA and in mitochondrial transcriptomes. This was associated with multiple abnormalities in mitochondrial function, including altered mitochondrial structure, low oxidative phosphorylation (OXPHOS), decreased ATP production, reduced mitophagy, decreased mtDNA copy number, and activation of mitochondrial apoptosis. These alterations in mitochondrial metabolism were associated with changes in tumor phenotype and in pathways involved in cell mitophagy, mitochondrial apoptosis, and epigenetic regulation. We further showed that the RNA-shuttling protein HuR and the mitochondria transmembrane protein MTCH2 mediated the transport of MALAT1 in this nuclear-mitochondrial crosstalk. This study provides the first evidence that the nuclear genome-encoded lncRNA MALAT1 functions as a critical epigenetic player in the regulation of mitochondrial metabolism of hepatoma cells, laying the foundation for further clarifying the roles of lncRNAs in tumor metabolic reprogramming.MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. https://www.selleckchem.com/products/kira6.html We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group's differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

65%). The difference between potential and estimated deaths is higher among women in the age classes between 30 and 74 years.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritinPre-HCT) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritinPost-HCT) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritinPost-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritinPost-HCT (≤ 3169 vs > 3169 ng/mL) and ferritinPre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritinPost-HCT group, the high ferritinPost-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p  less then  0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p  less then  0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritinPost-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p  less then  0.001, HR = 3.905). However, ferritinPre-HCT did not stratify well for OS or NRM. FerritinPost-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritinPre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. https://www.selleckchem.com/products/bapta-am.html Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.Anthropogenic nitrogen (N) deposition is significantly altering both community structure and ecosystem processes in terrestrial ecosystems across the globe. However, our understanding of the consequences of N deposition in dryland systems remains relatively poor, despite evidence that drylands may be particularly vulnerable to increasing N inputs. In this study, we investigated the influence of 7 years of multiple levels of simulated N deposition (0, 2, 5, and 8 kg N ha-1 year-1) on plant community structure and biological soil crust (biocrust) cover at three semi-arid grassland sites spanning a soil texture gradient. Biocrusts are a surface community of mosses, lichens, cyanobacteria, and/or algae, and have been shown to be sensitive to N inputs. We hypothesized that N additions would decrease plant diversity, increase abundance of the invasive annual grass Bromus tectorum, and decrease biocrust cover. Contrary to our expectations, we found that N additions did not affect plant diversity or B. tectorum abundance. In partial support of our hypotheses, N additions negatively affected biocrust cover in some years, perhaps driven in part by inter-annual differences in precipitation. Soil inorganic N concentrations showed rapid but ephemeral responses to N additions and plant foliar N concentrations showed no response, indicating that the magnitude of plant and biocrust responses to N fertilization may be buffered by endogenous N cycling. More work is needed to determine N critical load thresholds for plant community and biocrust dynamics in semi-arid systems and the factors that determine the fate of N inputs.

It is concluded that gonadotropin-releasing hormone analog treatment increases body mass index during treatment and when patients reach the final height, they return to their pretreatment body mass index. Younger age and greater height at the time of diagnosis are the positive factors on final height. We found that between the ages of 6-9.8 years, girls with central precocious puberty who received gonadotropin-releasing hormone analog treatment reached a final height within their target height range. It is concluded that gonadotropin-releasing hormone analog treatment increases body mass index during treatment and when patients reach the final height, they return to their pretreatment body mass index. Younger age and greater height at the time of diagnosis are the positive factors on final height. Allergic sensitization in infancy generally develops against food allergens. We aimed to investigate the frequency of aero-allergens sensitization at older ages in infants with food allergy. This retrospective cross-sectional study was conducted in Dr. Behçet Uz Children's Allergy Clinic. Infants with confirmed IgE-mediated food allergy between January 1 , 2004, and December 31 , 2016, were evaluated for aero-allergen sensitivities through skin prick tests (SPT) after at least two years after diagnosis, and the data were compared with a healthy control group. A total of 187 cases, 87 of which were patients, were included in the study. The cause of food allergies was cow's milk only in 24 (27.6%) cases, egg only in 26 (29.9%) cases, both cow's milk and egg in 33 (37.9%) cases, fish only in two cases (2.3%), and both fish and egg in two (2.3%) cases. The mean age at which the aero-allergen SPT was performed was 65 (46-180) months in the patient group and 72 (48-132) months in the healthy control group. In the patient group, 39 (44.8%) had aero-allergen sensitization, whereas, in the healthy control group, five (5%) had aero-allergen sensitization. Aero-allergen sensitization was more frequent in the patient group (p<0.05). There was no statistically significant difference in the type and number of food allergies and the development of aero-allergen sensitization (p>0.05). In infants with food allergies, sensitization may develop with aero-allergens at an early age. Clinical follow-up of these patients may be important in terms of allergic respiratory diseases. In infants with food allergies, sensitization may develop with aero-allergens at an early age. Clinical follow-up of these patients may be important in terms of allergic respiratory diseases.In recent years, the use of point-of-care ultrasound by non-radiologist physicians has become widespread. Especially for clinicians working in pediatric emergency departments and pediatric intensive care units, point-of-care ultrasound has almost become a part of physical examinations due to the rapid responses it offers to the problems of critically ill patients. Numerous studies revealed the important clinical benefits of point-of-care ultrasound use by pediatric intensive care providers. In this review, we aimed to give detailed information about different types of point-of-care ultrasound applications in pediatric intensive care units and wanted to draw attention to the increased use and clinical benefits of this noninvasive and radiation free technique.Due to the COVID-19 pandemic, more than 90% of students worldwide were affected by education loss. Moreover, for school-age children and adolescents, there may be worsening of nutrition, increasing mental health disorders, lack of physical activity, and related deleterious consequences raise concerns about negative habits, child violence, and abuse. Face-to-face education in schools provides positive educational opportunities that cannot be achieved with online education. In studies from various countries, children have milder disease, constituting as little as 1-8% of all laboratory-confirmed COVID-19 cases, with less transmission capacity to household contacts than adults (0.5-7% vs. 10-20%). Symptomatic or asymptomatic children can infect other people less than adults. Also, the transmission of illness between students at school is less than expected, and the transmission of COVID-19 to students is usually acquired from sick adults rather than sick students. Therefore, with suitable measures, infection risk is less than expected and seems not to be higher than in other public places. COVID-19 measures in schools can be summarized as follows avoiding crowded/close contact environments as much as possible, respecting the protective (social) distance, wearing appropriate masks, hand hygiene, and some essential protective measurements of classrooms and environment. Measurements should be participatory (students, teachers, education staff, parents, administration), applicable, sustainable, and flexible according to the conditions. Eltrombopag is recommended for the treatment of refractory immune thrombocytopenia (ITP). Based on its half-life, it may be practical to use an intermittent dosage. Our aim was to compare the effectiveness and safety of intermittent vs daily eltrombopag dosage protocols for the treatment of primary ITP refractory to prior therapies. This was a retrospective study, and 34 adult primary ITP patients refractory to prior therapies were included in our analysis. Eltrombopag was used in this study. The patients were divided into daily eltrombopag dosage and intermittent eltrombopag dosage groups. Eltrombopag effectiveness was assessed regarding platelet count and bleeding resolution. https://www.selleckchem.com/products/geldanamycin.html Safety was assessed via adverse events reporting. In the daily eltrombopag dosage group, overall response (OR), complete response (CR), partial response (PR), and relapse rates were 69.23%, 53.85%, 15.38%, and 30.77%, respectively. In the intermittent eltrombopag dosage group, OR, CR, PR, and relapse rates were 68.75%, 50%, 18.75%, and 31.25%, respectively. Comparison between daily and intermittent eltrombopag dosage groups as regards CR, PR, relapse, relapse-free survival and adverse events showed insignificant differences. Intermittent eltrombopag dosage is safe and effective in patients with ITP refractory to prior therapies and comparable to the daily eltrombopag dosage. Intermittent eltrombopag dosage is safe and effective in patients with ITP refractory to prior therapies and comparable to the daily eltrombopag dosage.

Taken together, the results indicate that muscle-derived lumican stimulates bone formation via integrin α2β1 and the downstream ERK signal, indicating that this is a potential therapeutic target for metabolic bone diseases.Cdr1as is the abundant circular RNA (circRNA) in human and vertebrate retinas. However, the role of Cdr1as in the retina remains unknown. In this study, we aimed to generate a Cdr1as knockout (KO) mouse model and investigate the retinal consequences of Cdr1as loss of function. Through in situ hybridization (ISH), we demonstrated that Cdr1as is mainly expressed in the inner retina. Using CRISPR/Cas9 targeting Cdr1as, we successfully generated KO mice. We carried out ocular examinations in the KO mice until postnatal day 500. Compared with the age-matched wild-type (WT) siblings, the KO mice displayed increased b-wave amplitude of photopic electrophysiological response and reduced vision contrast sensitivity. Through small RNA profiling of the retinas, we determined that miR-7 was downregulated, while its target genes were upregulated. Taken together, our results demonstrated for the first time that Cdr1as ablation led to a mild retinal consequence in mice, indicating that Cdr1as abundance is not indispensable for retinal development and maintenance. Leukocyte-mediated inflammation is crucial in ST-segment elevation myocardial infarction (STEMI). We recently observed that neutrophil extracellular traps (NETs) are increased at the culprit site, promoting activation and differentiation of fibrocytes, cells with mesenchymal and leukocytic properties. https://www.selleckchem.com/products/tc-s-7009.html Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 and C-C chemokine receptor type 2 (CCR2). We investigated the interplay between NETs, fibrocyte function, and MCP-1 in STEMI. Culprit site and peripheral blood samples of STEMI patients were drawn during primary percutaneous coronary intervention. MCP-1 and the NET marker citrullinated histone H3 (citH3) were measured by ELISA while double-stranded DNA was stained with a fluorescent dye. The influence of MCP-1 on NET formation was assessed using isolated healthy donor neutrophils. Human coronary artery endothelial cells (hCAECs) were stimulated with isolated NETs, and MCP-1 gene expression was measured by ELISA and qPCR. CCR2 exprhelial cells. MCP-1 facilitates further NETosis. Monocytes enter the culprit site along an MCP-1 gradient, to transdifferentiate into fibrocytes in the presence of NETs. NETs function as signaling scaffolds at the culprit site of STEMI. NETs assist MCP-1 and ICAM-1 release from culprit site coronary artery endothelial cells. MCP-1 facilitates further NETosis. Monocytes enter the culprit site along an MCP-1 gradient, to transdifferentiate into fibrocytes in the presence of NETs.Cholesterol biosynthesis is a multi-step process involving several subcellular compartments, including peroxisomes. Cells adjust their sterol content by both transcriptional and post-transcriptional feedback regulation, for which sterol regulatory element-binding proteins (SREBPs) are essential; such homeostasis is dysregulated in peroxisome-deficient Pex2 knockout mice. Here, we compared the regulation of cholesterol biosynthesis in Chinese hamster ovary (CHO-K1) cells and in three isogenic peroxisome-deficient CHO cell lines harboring Pex2 gene mutations. Peroxisome deficiency activated expression of cholesterogenic genes, however, cholesterol levels were unchanged. 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) protein levels were increased in mutant cells, whereas HMGCR activity was significantly decreased, resulting in reduced cholesterol synthesis. U18666A, an inhibitor of lysosomal cholesterol export, induced cholesterol biosynthetic enzymes; yet, cholesterol synthesis was still reduced. Interestingly, peroxisome deficiency promoted ER-to-Golgi SREBP cleavage-activating protein (SCAP) trafficking even when cells were cholesterol-loaded. Restoration of functional peroxisomes normalized regulation of cholesterol synthesis and SCAP trafficking. These results highlight the importance of functional peroxisomes for maintaining cholesterol homeostasis and efficient cholesterol synthesis. ) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis. This study aimed to investigate the mechanisms of CGA in infection. The intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on infection. The antibacterial effects of CGA on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation- and autophagy-related proteins was detected. CGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in infection. The functional rescue experiments of miR-23a and PTEN further identified these effects. CGA promotes autophagy and inhibits infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway. CGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.Circular RNAs (circRNAs) are recognized as functional non-coding transcripts; however, emerging evidence has revealed that some synthetic circRNAs generate functional peptides or proteins. Additionally, the diverse biological functions of circRNAs include acting as miRNA-binding sponges, RNA-binding protein regulators, and protein translation templates. Previously, we found that circular RNA circFAM188B is a stable circular RNA and differentially expressed between broiler chickens and layers during embryonic skeletal muscle development. In this study, we found that circFAM188B exhibited a unique pattern of sharply decreased expression from embryonic day 10 (E10) to Day 35 (D35) after hatching. Our experimental results showed that circFAM188B promotes the proliferation, but inhibits the differentiation of chicken skeletal muscle satellite cells (SMSCs). Bioinformatic analysis revealed circFAM188B contain an opening reading frame (ORF) which translate into circFAM188B-103aa, internal ribosome entry site (IRES) analysis further confirmed the coding potential of circFAM188B.

Clostridium perfringens (CP) is the etiologic agent of necrotic enteritis (NE) in broiler chickens that is responsible for massive economic losses in the poultry industry in response to voluntary reduction and withdrawal of antibiotic growth promoters. Large variations exist in the CP isolates in inducing intestinal NE lesions. However, limited information is available on CP isolate genetics in inducing NE with other predisposing factors. This study investigated the ability of five CP isolates from different sources to influence NE pathogenesis by using an Eimeria maxima (EM) coinfection NE model Str.13 (from soil), LLY_N11 (healthy chicken intestine), SM101 (food poisoning), Del1 (netB+tpeL-) and LLY_Tpel17 (netB+tpeL+) for NE-afflicted chickens. The 2-wk-old broiler chickens were preinfected with EM (5 × 103 oocysts) followed by CP infection (around 1 × 109 colony-forming units per chicken). The group of the LLY_Tpel17 isolate with EM coinfection had 25% mortality. No mortality was observed in the groups infected with EM alone, all CP alone, or dual infections of EM/other CP isolates. In this model of EM/CP coinfections, the relative percentages of body weight gain showed statistically significant decreases in all EM/CP groups except the EM/SM101 group when compared with the sham control group. Evident gut lesions were only observed in the three groups of EM/LLY_N11, EM/Del1, and EM/LLY_Tpel17, all of which possessed an essential NE pathogenesis locus in their genomes. Our studies indicate that LLY_Tpel17 is highly pathogenic to induce severe gut lesions and would be a good CP challenge strain for studies investigating pathogenesis and evaluating the protection efficacy for antibiotic alternative approaches.Necrotic enteritis (NE) is a common and costly disease of poultry caused by virulent toxigenic strains of Clostridium perfringens. Although the importance of trace minerals for intestinal integrity and health is well documented, there is little information on their role in ameliorating the effects of NE. The two studies reported here examined the effects of replacing a portion of the dietary zinc (Zn), copper (Cu), and manganese (Mn) supplied as sulfates in the control diets with metal-amino acid-complexed minerals in a NE-challenge model consisting of coccidiosis and Clostridium perfringens. In a 28-day battery study, the treatments were the following (1) no additional Zn or Mn, unchallenged (negative control); (2) no added Zn or Mn, challenged (positive control); (3) added ZnSO4 and MnSO4 at 100 ppm each, challenged; (4) additional ZnSO4 at 60 ppm, Availa-Zn at 40 ppm (Low), and MnSO4 at 100 ppm, challenged; (5) added ZnSO4 at 60 ppm, Availa-Zn at 60 ppm (high), and MnSO4 at 100 ppm, challenged; and (6) add 100, 100, and 20 ppm, respectively (Zoetis, Inc., Kalamazoo, MI). None of the treatments reduced lesion scores. The Availa-Zn and Availa-Zn/Mn had lower mortality than the sulfate-supplemented feed, whereas Availa-Zn/Cu and bacitracin methylene disalicylate were intermediate and did not differ from the other groups. Considering both trials together, and by using NE mortality as the discriminating factor, we found that adding Zn and Mn exceeding National Research Council requirements reduced NE-associated mortality, and in the floor pen study, complexed Zn and complexed Zn plus Mn appeared to be superior to sulfates.Marek's disease (MD) is an oncogenic, lymphoproliferative, and highly contagious disease of chickens. Its etiologic agent is the alphaherpesvirus Marek's disease virus (MDV, Gallid alphaherpesvirus 2), and it is a chronic and ubiquitous problem for the poultry industry with significant economic impact in the United States and worldwide. We have previously demonstrated that MDV attenuated by dicodon deoptimization of the UL54 gene results in reduced gene product accumulation in vitro, with reduced viral genome copy number upon infection and reduced atrophy of bursa and thymus in vivo as well. In this report we detail our attempts to use the same attenuation strategy on a meq-deleted MDV mutant, rMd5B40ΔMeq. Unlike the wild-type rMd5B40 virus the rMd5B40ΔMeq is no longer oncogenic, but infected birds experience an unacceptable amount of bursa and thymus atrophy (BTA). We produced two meq-deleted MDV recombinants with a dicodon-deoptimized UL54 (rMd5B40ΔMeq/UL54deop1 and -deop2) and tested their tendency to cause BTA and to serve as a protective vaccine. We found that, although dicodon deoptimization of the UL54 gene results in a virus that spares the infected animal from atrophy of the bursa and thymus, the meq-deleted UL54-deoptimized recombinant is also less protective than the meq-deleted virus without UL54 deoptimization, the HVT + SB1 combination vaccine, or the Rispens (CVI988) vaccine.Necrotic enteritis (NE) is an important enteric disease affecting a wide variety of avian species, including poultry, caused by Clostridium perfringens type G and, rarely, type C. Significant economic losses can result from elevated mortality rates and poor performance, such as decreased weight gain associated with intestinal damage and impaired absorption of nutrients. Additional losses can result from elevated condemnation at the processing plant because of a high incidence of cholangiohepatitis. Nonenteric lesions associated with NE have been rarely reported. This paper describes uncommon presentations of NE in commercial chickens received by the California Animal Health and Food Safety Laboratory (Turlock and Tulare branches) between 2009 and 2018. Overall, extraintestinal lesions associated with C. perfringens were diagnosed in 25 cases of NE involving commercial broiler chickens. The extraintestinal sites most commonly affected included liver, followed by gizzard, bursa of Fabricius, gall bladder, and spleen. https://www.selleckchem.com/products/ceftaroline-fosamil.html The etiology of these lesions, C. perfringens, was confirmed from a combination of gross, bacteriologic, microscopic, and immunohistochemical findings. The most common predisposing factors for NE identified were coccidiosis (56%, 14/25) and immunosuppressive disease agents, including infectious bursal disease virus (16%, 4/25) and fowl adenovirus group 1 (4%, 1/25). Additionally, four cases (16%) had microscopic lesions compatible with cystic enteritis, probably of viral etiology. This study describes the incidence of extraintestinal lesions of NE in chickens, underlying the role of enteric disorders and immunosuppression as major predisposing factors for the development of NE.

Following this shift, changes in dust and productivity largely track the glacial-interglacial cycles of the late Pliocene and early Pleistocene epochs. On the basis of this pattern, we infer that shifts in the westerlies were primarily driven by variations in Plio-Pleistocene thermal gradients and ice volume. By combining this relationship with other dust records9-11 and climate modelling results12, we find that the proposed changes in the westerlies were globally synchronous. If the Pliocene is predictive of future warming, we posit that continued poleward movement and weakening of the present-day westerlies in both hemispheres can be expected.Crystal defects affect the thermal and heat-transport properties of materials by scattering phonons and modifying phonon spectra1-8. To appreciate how imperfections in solids influence thermal conductivity and diffusivity, it is thus essential to understand phonon-defect interactions. Sophisticated theories are available to explore such interactions, but experimental validation is limited because most phonon-detecting spectroscopic methods do not reach the high spatial resolution needed to resolve local vibrational spectra near individual defects. Here we demonstrate that space- and angle-resolved vibrational spectroscopy in a transmission electron microscope makes it possible to map the vibrational spectra of individual crystal defects. We detect a red shift of several millielectronvolts in the energy of acoustic vibration modes near a single stacking fault in cubic silicon carbide, together with substantial changes in their intensity, and find that these changes are confined to within a few nanometres of the stacking fault. These observations illustrate that the capabilities of a state-of-the-art transmission electron microscope open the door to the direct mapping of phonon propagation around defects, which is expected to provide useful guidance for engineering the thermal properties of materials.With the proliferation of ultrahigh-speed mobile networks and internet-connected devices, along with the rise of artificial intelligence (AI)1, the world is generating exponentially increasing amounts of data that need to be processed in a fast and efficient way. Highly parallelized, fast and scalable hardware is therefore becoming progressively more important2. Here we demonstrate a computationally specific integrated photonic hardware accelerator (tensor core) that is capable of operating at speeds of trillions of multiply-accumulate operations per second (1012 MAC operations per second or tera-MACs per second). The tensor core can be considered as the optical analogue of an application-specific integrated circuit (ASIC). It achieves parallelized photonic in-memory computing using phase-change-material memory arrays and photonic chip-based optical frequency combs (soliton microcombs3). The computation is reduced to measuring the optical transmission of reconfigurable and non-resonant passive components and can operate at a bandwidth exceeding 14 gigahertz, limited only by the speed of the modulators and photodetectors. Given recent advances in hybrid integration of soliton microcombs at microwave line rates3-5, ultralow-loss silicon nitride waveguides6,7, and high-speed on-chip detectors and modulators, our approach provides a path towards full complementary metal-oxide-semiconductor (CMOS) wafer-scale integration of the photonic tensor core. Although we focus on convolutional processing, more generally our results indicate the potential of integrated photonics for parallel, fast, and efficient computational hardware in data-heavy AI applications such as autonomous driving, live video processing, and next-generation cloud computing services.Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection.Climate change alters frequencies and intensities of soil drying-rewetting and freezing-thawing cycles. https://www.selleckchem.com/products/ceftaroline-fosamil.html These fluctuations affect soil water availability, a crucial driver of soil microbial activity. While these fluctuations are leaving imprints on soil microbiome structures, the question remains if the legacy of one type of weather fluctuation (e.g., drying-rewetting) affects the community response to the other (e.g., freezing-thawing). As both phenomenons give similar water availability fluctuations, we hypothesized that freezing-thawing and drying-rewetting cycles have similar effects on the soil microbiome. We tested this hypothesis by establishing targeted microcosm experiments. We created a legacy by exposing soil samples to a freezing-thawing or drying-rewetting cycle (phase 1), followed by an additional drying-rewetting or freezing-thawing cycle (phase 2). We measured soil respiration and analyzed soil microbiome structures. Across experiments, larger CO2 pulses and changes in microbiome structures were observed after rewetting than thawing.

Proper diagnosis of the uncommon endocrine disturbance allowed targeted therapy and avoidance of neck exploration for wrongly suspecting primary hyperparathyroidism. Intact parathyroid hormone should be measured in cases of malignant hypercalcemia. Proper diagnosis of the uncommon endocrine disturbance allowed targeted therapy and avoidance of neck exploration for wrongly suspecting primary hyperparathyroidism. Intact parathyroid hormone should be measured in cases of malignant hypercalcemia. This study aimed to examine the association between overtime work and the frequency of preventive dental visits among workers in Japan. A self-administered questionnaire was completed by 14,847 daytime-workers. We used a logistic regression model stratified by sex and age and adjusted for marital status, occupation, education, and oral status to investigate the association between overtime work hours and the frequency of preventive dental visits. In total 1037 men (9.3%) and 511 women (13.9%) attended quarterly preventive dental visits, and 2672 men (23.9%) and 1165 women (31.8%) attended annual preventive dental visits. Overtime work was statistically significantly associated with quarterly preventive dental visits among men aged 50-59 years, with adjusted odds ratios (aOR) and 95% confidence intervals (CI) of 0.73 (0.56-0.95), 0.75 (0.54-1.04), and 0.55 (0.34-0.90) for < 20, 20-39, and ≥40 h overtime/month, respectively. No such trends were observed for men aged < 50 years and women of all ages. Overtime work of < 20, 20-40, and ≥40 h overtime/month was statistically significantly associated with annual preventive dental visits among men aged 40-49 years (aOR [95%CI] 0.76 [0.61-0.95], 0.84 [0.65-1.09], and 0.72 [0.51-1.00], respectively) and 50-59 years (aOR [95%CI] 0.75 [0.61-0.91], 0.76 [0.59-0.97], and 0.63 [0.45-0.88], respectively). No such trends were observed in men < 40 years and women of all ages. Our study revealed associations between overtime and preventive dental visits among male workers aged in their 40s and 50s. Our study revealed associations between overtime and preventive dental visits among male workers aged in their 40s and 50s. Pneumonia is one of the principal reasons for incidence and death in the world. The former research mainly concentrated on specific sources of patients. Besides, due to the heterogeneity among regions, there are inconsistencies in the outcome of these surveys. To explore the relationship between atmospheric pollution and hospital visits for pneumonia under the climate and pollution conditions in Qingdao, we carried out this study. The medical records of pneumonia patients were gathered from the affiliated hospital of Qingdao University during Jan 1st, 2014, and Dec 31st,2018. Daily concentrations of PM , PM , SO , NO , as well as CO, were collected from the national air quality monitoring stations in Qingdao. Case-crossover study design and conditional logistic regression model were used to estimate the associations. Daily temperature, relative humidity, and atmospheric pressure were adjusted as the covariates in all models. A principal component analysis was used to solve the multicollinearity betweencipal reason in inducing hospital visits for pneumonia. Our study found a significant relationship between short-term uncovering to PM2.5, PM10, NO2, SO2, and hospital visits for pneumonia in Qingdao. The effect of atmospheric pollutants mainly arose in a cold period. https://www.selleckchem.com/products/vx-561.html The particulate matter might be the principal reason in inducing hospital visits for pneumonia. Sugar-sweetened beverage (SSB) consumption is an important behavior that can influence individuals' risk for diabetes, obesity, and other chronic diseases. Nonetheless, there is a lack of valid measures to assess SSB-related constructs. Reliable and valid measures can help evaluate the efficacy of interventions designed to curb SSB consumption. Our aim was to develop a valid and reliable instrument to measure constructs related to SSB consumption in English and Spanish. A cross-sectional survey was conducted among a convenience sample of 150 adult residents of public housing developments in Boston, Massachusetts between July of 2016 and January of 2017. All households from two public housing developments were approached by study staff to solicit participation via door-to-door knocking and posted flyers. We developed questions to measure three SSB-related constructs informed by the Social Cognitive Theory SSB knowledge, and self-efficacy and intention to act on SSB consumption. The questions were pilot test-retest (ICC = 0.68), and significant correlation with intention and SSB consumption. Of the four intention items, one was significantly correlated with SSB consumption. This study provides evidence for the validity of key constructs related to SSB consumption for use in adults, which could provide important theory-based markers for program evaluations of SSB-related interventions. This study provides evidence for the validity of key constructs related to SSB consumption for use in adults, which could provide important theory-based markers for program evaluations of SSB-related interventions. It is uncertain whether increases in PaCO during surgery lead to an increase in plasma potassium concentration and, if so, by how much. Hyperkalaemia may result in cardiac arrhythmias, muscle weakness or paralysis. The key objectives were to determine whether increases in PaCO during laparoscopic surgery induce increases in plasma potassium concentrations and, if so, to determine the magnitude of such changes. A retrospective observational study of adult patients undergoing laparoscopic abdominal surgery was perfomed. The independent association between increases in PaCO and changes in plasma potassium concentration was assessed by performing arterial blood gases within 15min of induction of anaesthesia and within 15min of completion of surgery. 289 patients were studied (mean age of 63.2years; 176 [60.9%] male, and mean body mass index of 29.3kg/m ). At the completion of the surgery, PaCO had increased by 5.18mmHg (95% CI 4.27mmHg to 6.09mmHg) compared to baseline values (P < 0.001) with an associated increase in potassium concentration of 0.

[This corrects the article DOI 10.2147/DDDT.S46323.]. The aim of the present study was to evaluate the expression of inflammasome and cytokine on experimental periodontitis with super activated platelet lysate (SPL) in rats. Periodontitis was induced by submerging cotton ligatures on the right side of the maxillary second molar in 36 Wistar rats. The rats were divided into 3 groups randomly the rats received no treatment (control group); local injection with sterile saline (ligature+saline group) and local injection with SPL (ligature+SPL group). After treatments, the alveolar bone level and inflammation of periodontal tissue were evaluated by micro-computed tomography (micro-CT) scanning and histological examination, respectively. The expression of inflammasome and cytokine was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Compared with the control group, the bone loss significantly increased by 0.9 mm in the ligature+saline group and 0.4 mm in the ligature+SPL group (P < 0.001). 0.5 mm reduction in the bone loss was founded in the ligature+SPL group compared with the ligature+saline group (P < 0.001). https://www.selleckchem.com/products/thymidine.html The gene expression of was significantly reduced in the ligature+SPL group compared with the ligature+saline group (P < 0.05). Compared with the ligature+saline group, the expression for inflammasome was both downregulated in the ligature+SPL group (P < 0.05). Our present study demonstrated local injection of SPL regulated the expression of inflammasome and cytokine and had a visible effect of relieving inflammation in the experimental periodontitis in rats. Our present study demonstrated local injection of SPL regulated the expression of inflammasome and cytokine and had a visible effect of relieving inflammation in the experimental periodontitis in rats. Osteoarthritis (OA) is a prevalent articular disorder and has no entirely satisfactory treatment. Punicalagin (PUG) is a polyphenol which has shown multiple pharmacological effects on various diseases. However, the role of PUG in the treatment of OA has not been well defined. The effects of PUG on anti-oxidative stress, anti-apoptosis, extracellular matrix (ECM) degradation and autophagy were evaluated in chondrocytes through Western blot and immunofluorescence (IF) staining. Meanwhile, the effects of PUG on destabilization of the medial meniscus (DMM) model were also assessed in vivo by performing histopathologic analysis and IF staining. In vitro, PUG treatment not only increased the level of HO-1 and SOD1 against oxidative stress but also suppressed the expression of apoptotic proteins and inhibited ECM degradation. Meanwhile, PUG treatment activated autophagy and restores autophagic flux in chondrocytes after tert-butyl hydroperoxide (TBHP) insult, inhibition of autophagy by 3-methyladenine (3-MA) partly abrogated the protective effects of PUG on chondrocytes. In vivo, degeneration of the articular cartilage following DMM was also ameliorated by PUG treatment. PUG prevents the progression of OA through inhibition of apoptosis, oxidative stress and ECM degradation in chondrocytes, which mediated by the activation of autophagy. PUG prevents the progression of OA through inhibition of apoptosis, oxidative stress and ECM degradation in chondrocytes, which mediated by the activation of autophagy. We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile. Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired -test and signed rank test. A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A-B, 93.7% with undetectable HIV-viral load. Mean age was 46.7±10.7 years, body mass index was 25.0±3.9 kg/m , median CD4 cell count was 634 cell/µL (interquartile range [IQR]=439-900), aspartate aminotransferase (AST) was 23 (IQR=19-30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17-34) IU/L. At T1, both AST (median=-1, IQR=-5-2 IU/L, =0.004) and ALT (median=-2, IQR=-7-3 IU/L, =0.0004) showed a significant decrease. Among 28 patients with ALT >40 at baseline, reduction was significant both clinically (-17, IQR=-32--1) and statistically ( =0.0003). Total cholesterol levels (TC) increased (+13.4±3.8 mg/dL, =0.0006), as well as HDL-cholesterol (HDL-C) (+3.8±1.2 mg/dL, =0.02), LDL Cholesterol (LDL-C) (+7.6±3.4, =0.03) and glucose (+4.0±1.8 mg/dL, =0.02). DAD and Framingham risk score did not change at 6 months after switch. A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT >40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores. 40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores. To describe the anatomical and functional results of the implantation of asymmetric thickness intracorneal ring segments (AS-ICRS) in eyes with keratoconus and asymmetric/irregular astigmatism (type 2 - and type 3 - phenotypes, Fernandez-Vega/Alfonso morphologic Keratoconus classification). Retrospective observational study including 19 consecutive patients (21 eyes) with keratoconus who underwent manual implantation of the Keraring Asymmetric ICRS (AS). Analysis included demographic and clinical data and Pentacam (Oculus ) measurements topographic astigmatism; topographic flat meridian (K1), steepest meridian (K2) and the maximum keratometric point (Kmax); total root mean square (RMS) and high order RMS (HOA) aberrations and comatic Zernike coefficients (Z3 ;Z3 ) at 0º and 90º meridians. Overall mean age was 35.3±11.7 years and median follow-up was 7.1 months (range 6-12). At the end of follow-up, a significant improvement from baseline was achieved in both UDVA (0.24±0.22; p=0.017) and CDVA (0.