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- ArticleSasaki H, Hayashi K, Imamura M, Hirota Y, Hosoki H, Nitta L, Furutani A, Shibata S.J Nutr Biochem. 2023 10;120:109420.The consumption of resistant dextrin improves constipation, while its fermentation and degradation by the intestinal microbiota produce short-chain fatty acids (SCFA) and lactic acid, which have beneficial effects on host metabolism and immunity. Mg oxide (MgO) is an important mineral that is used to treat constipation. Therefore, resistant dextrin and MgO are often administered together to improve constipation. However, limited information is available regarding the effect of this combination on SCFA and lactic acid production. Crl:CD1(ICR) mice were fed a Mg-free diet with 5% resistant dextrin, followed by oral administration of MgO. We collected the cecum contents and measured SCFA and lactic acid levels. Additionally, the human subjects received resistant dextrin and Mg supplements as part of their habitual diet. The results of this study demonstrate that intestinal microbiota cannot promote SCFA and lactic acid production in the absence of Mg. In a mouse model, low doses of MgO promoted the production of SCFA and lactic acid, whereas high doses decreased their production. In humans, the combined consumption of resistant dextrin and Mg supplements increased the production of SCFA and lactic acid. The production of SCFA and lactic acid from dietary fiber may be augmented by the presence of MgO.
- ArticleAbd Rahim NH, Satyanarayana B, Ibrahim YS, Not C, Idris I, Mohd Jani J, Cannicci S, Dahdouh-Guebas F.Data Brief. 2023 Aug;49:109420.The present dataset provides information on the abundance of microplastics (MPs) in relation to different feeding habits of the four mangrove brachyuran crab species namely, Parasesarma eumolpe, Austruca annulipes, Metaplax elegans and Scylla olivacea at Setiu Wetlands in Peninsular Malaysia. Three sites namely, Pulau Layat (upstream, close to the core mangrove zone), Kampung Pengkalan Gelap (midstream, close to the settlements), and Pulau Sutung (downstream, close to the shifted river mouth) were chosen for the sample collection (through hand catch method and traps) in both the dry (Feb-Mar 2021) and the wet (Dec 2021 - Jan 2022) seasons. The cardiac stomach of each crab was dissected, digested in potassium hydroxide and then filtered through a 1.6 µm pore size glass fibre filter using the vacuum pump. The abundance, type and colour of MPs per crab individual were determined under a stereomicroscope (Carl Zeiss Stemi 508, China) attached to the digital camera (Axiocam 208 colour). The general abundance of MPs was found in the order of carnivorous S. olivacea > microphytobenthos feeder A. annulipes > herbivorous P. eumolpe > detritivorous M. elegans. The data also reveal morphometric measurements such as body weight, gut weight, carapace width and carapace length of the crab specimens. The information given in this article is useful for study replications and scientific comparisons, especially with brachyuran crabs and other organisms with similar feeding guilds, in the mangroves of Malaysia and elsewhere.
- ArticleChen T, Le Bizec B, Dervilly G.Steroids. 2024 Jun;206:109420.The use of steroids in livestock animals is a source of concern for consumers because of the risks associated with the presence of their residues in foodstuffs of animal origin. Technological advances such as mass spectrometry have made it possible to play a fundamental role in controlling such practices, firstly for the discovery of marker metabolites but also for the monitoring of these compounds under the regulatory framework. Current control strategies rely on the monitoring of either the parent drug or its metabolites in various matrices of interest. As some of these steroids also have an endogenous status specific strategies have to be applied for control purposes. This review aims to provide a comprehensive and up-to-date knowledge of analytical strategies, whether targeted or non-targeted, and whether they focus on markers of exposure or effect in the specific context of chemical food safety regarding the use of anabolic steroids in livestock. The role of new approaches in data acquisition (e.g. ion mobility), processing and analysis, (e.g. molecular networking), is also discussed.
- ArticleLiu Y, Zhao Y, Shukha Y, Lu H, Wang L, Liu Z, Liu C, Zhao Y, Wang H, Zhao G, Liang W, Fan Y, Chang L, Yurdagul A, Pattillo CB, Orr AW, Aviram M, Wen B, Garcia-Barrio MT, Zhang J, Liu W, Sun D, Hayek T, Chen YE, Rom O.Cell Rep. 2021 07 27;36(4):109420.Dysregulated glycine metabolism is emerging as a common denominator in cardiometabolic diseases, but its contribution to atherosclerosis remains unclear. In this study, we demonstrate impaired glycine-oxalate metabolism through alanine-glyoxylate aminotransferase (AGXT) in atherosclerosis. As found in patients with atherosclerosis, the glycine/oxalate ratio is decreased in atherosclerotic mice concomitant with suppression of AGXT. Agxt deletion in apolipoprotein E-deficient (Apoe-/-) mice decreases the glycine/oxalate ratio and increases atherosclerosis with induction of hepatic pro-atherogenic pathways, predominantly cytokine/chemokine signaling and dysregulated redox homeostasis. Consistently, circulating and aortic C-C motif chemokine ligand 5 (CCL5) and superoxide in lesional macrophages are increased. Similar findings are observed following dietary oxalate overload in Apoe-/- mice. In macrophages, oxalate induces mitochondrial dysfunction and superoxide accumulation, leading to increased CCL5. Conversely, AGXT overexpression in Apoe-/- mice increases the glycine/oxalate ratio and decreases aortic superoxide, CCL5, and atherosclerosis. Our findings uncover dysregulated oxalate metabolism via suppressed AGXT as a driver and therapeutic target in atherosclerosis.
- ArticleZhang L, Zhang C, Xing Z, Lou C, Fang J, Wang Z, Li M, He H, Bai H.Int Immunopharmacol. 2022 Dec;113(Pt A):109420.OBJECTIVE: Intercellular communication in the tumor microenvironment is a potential regulator of metastasis. To explore the specific mechanism, we performed a multi-omics analysis of hepatocellular carcinoma.
MATERIALS AND METHODS: Multiple omics data including scRNA-seq, ATAC-seq, RNA-seq, and methylation data were obtained from GEO and TCGA databases. SCENIC was used to identify key transcription factors and their Regulatory networks. ScMLnet was used to explore the mechanism of intercellular communication in the microenvironment. Multiple omics studies based on RNA-seq, ATAC-seq, and methylation data were used to explore downstream mechanisms of key transcription factors. Based on the analysis of cell differentiation trajectory and transcription subtypes, the regulation of cell communication on tumor subtypes was studied, and possible therapeutic compounds were explored. The universality of this mechanism was investigated by post-Pan-cancer analysis.
RESULTS: JUN and its regulatory network play a key role in HCC, which was mainly positively correlated with tumor-associated macrophages and fibroblasts. Intercellular communication analysis showed that macrophage and fibroblast-derived FN1 could increase JUN by TNFRSF11B/SMAD3. Multiomics analysis showed that KIF13A was a key downstream gene of JUN, which was involved in the activation of the hippo pathway. Analysis of cell differentiation trajectory, transcriptome subtypes, and neural network modeling showed that intercellular communication in the microenvironment can regulate the transcriptome characterization of HCC. Pan-cancer analysis indicates that this mechanism may be universal.
CONCLUSION: FN1 derived from tumor-associated macrophages and fibroblasts promotes metastasis and alters transcriptome subtypes through the JUN-Hippo signaling pathway in HCC, which may be universal in cancers. - ArticleGalligan BP, McClanahan TR.iScience. 2024 Apr 19;27(4):109420.The need to enhance nutrient production from tropical ecosystems to feed the poor could potentially create a new framework for fisheries science and management. Early recommendations have included targeting small fishes and increasing the species richness of fish catches, which could represent a departure from more traditional approaches such as biomass-based management. To test these recommendations, we compared the outcomes of biomass-based management with hypothesized factors influencing nutrient density in nearshore artisanal fish catches in the Western Indian Ocean. We found that enhancing nutrient production depends primarily on achieving biomass-based targets. Catches dominated by low- and mid-trophic level species with smaller body sizes and faster turnover were associated with modest increases in nutrient densities, but the variability in nutrient density was small relative to human nutritional requirements. Therefore, tropical fishery management should focus on restoring biomass to achieve maximum yields and sustainability, particularly for herbivorous fishes.
- ArticleFu Y, Cao Y, Chang Z, Zou C, Jiang D, Gao H, Jia C.Meat Sci. 2024 Mar;209:109420.The antifreeze activity of Flammulina velutipes polysaccharide (FVP) autoclave-extracted with dilute alkaline and effects of FVP on moisture status, size of ice crystals, physical and chemical characteristics of beef patties during repeated freeze-thaw (F-T) cycles were investigated. Results showed that FVP exhibited ice recrystallization inhibition activity and was able to alter the onset freezing/melting temperature of beef patties. 0.01% FVP significantly alleviated (P < 0.05) the decrement in water holding capacity by inhibiting water migration, restraining the mobility of water, and reducing the size of ice crystals of beef patties during the repeated F-T cycles. In addition, FVP could effectively inhibited oxidation reaction and protein aggregation of beef patties with significant decreases in TBARS value, protein turbidity, contents of total sulfhydryl and carbonyl of myofibrillar protein, and an increase in protein solubility during the repeated cycles. These results suggest FVP could be developed to be a promising cryoprotectant in frozen patties.
- ArticleGirkin CA, Garner MA, Fazio MA, Clark ME, Karuppanan U, Hubbard MG, Bianco G, Hubbard ST, Fortune B, Gross AK.Exp Eye Res. 2023 04;229:109420.PURPOSE: The relationships between intraocular pressure (IOP), ocular perfusion pressure (OPP), retinal perfusion, and retinal electrophysiologic responses have been explored experimentally across several animal models. These studies have demonstrated that elevated IOP reduces OPP, and when this reduction in OPP exceeds the autoregulatory capacity of the retina vasculature, retinal perfusion and electrophysiologic responses are reduced. This study aimed to evaluate these interactions for the first time in the living human eye.
METHODS: Five eyes from three research-consented brain-dead organ donors underwent optical coherence tomography with angiographic (OCT/A; Spectralis, Heidelberg Engineering) and electroretinographic (ERG, Diagnosys LLC) measurements while IOP was manometrically-elevated stepwise to pressures of 10, 30 and 50 mmHg. Systemic blood pressure (BP) was monitored continuously during testing. Correlation analysis was applied to assess association between ERG and OPP changes. In a single eye, prolonged IOP elevation was induced with viscoelastic injection and serial ERG measurements were obtained.
RESULTS: Reductions in inner retinal function defined by photopic ERG were observed with elevation in IOP and concomitant reduction in OPP. Reductions, especially in b-wave, and photopic negative response (PhNR) amplitudes and implicit times were significantly correlated with elevation in IOP and reduction in OPP. There were more appreciable changes in perfusion and functional responses in eyes tested while systemic blood pressure was lower. With prolonged IOP elevation, selective loss of the PhNR response was observed.
CONCLUSIONS: In the living human eye, retinal perfusion and inner retinal function are acutely impacted by elevation of IOP, and this impact is related to systemic BP and OPP. This novel approach provides a viable model to study the autoregulatory responses to IOP elevation in the living human eye. - ArticleFeng J, Su M, Li K, Ma J, Li R, Bai L, Wang X, Wang J, Yang Z.Vet Microbiol. 2022 Jun;269:109420.The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) variants represents a threat to public health. tet(X4) is highly endemic in northwestern China. Here, we extended the region to western China to further understand its epidemiology and distribution. During 2018-2020, 1497 faecal samples from pigs, sheep and goats in western China were screened for tet(X4)-positive strains. A total of 134 tigecycline-nonsusceptible Escherichia coli were isolated; among them, the largest number were isolated from Guangxi (66.42%, 89/134), Shaanxi (17.16%, 23/134) and Ningxia (8.21%, 11/134). Antibiotic susceptibility testing showed that all of these isolates were multidrug-resistant bacteria that were also resistant to florfenicol. Eighty-nine of 134 tet(X4)-positive Escherichia coli were analysed by whole-genome sequencing. They belonged to twenty-seven sequence types, and ST10, ST48, ST189 and ST2223 were the main types of Escherichia coli. Seventy-six of the 134 tet(X4)-positive Escherichia coli could transfer tet(X4) into the recipient Escherichia coli 26 R 793. Southern blot analysis showed that there were multiple plasmids carrying the tet(X4) gene in a single strain. The plasmids of the 89 tet(X4)-bearing isolates in this study were analysed. tet(X4)-bearing plasmids ranged from 20 to 400 kb, and the main plasmid types were categorised as IncX1, IncY, and ColRNAI. Guangxi, Ningxia, and Shanxi are likely to be the seminal and most affected areas. Additional efforts are needed to evaluate the impact of the spread of these tigecycline resistance genes and tigecycline-resistant isolates.
- ArticleParulekar M, Kazmerski TM, Gordon D, Syed T, Waters JFR, Van Cott AC, Kirkpatrick L.Epilepsy Behav. 2023 Oct;147:109420.OBJECTIVE: To develop online patient education materials about epilepsy for adolescent and young adult females with epilepsy through co-production in partnership with patients, parents or caregivers, and multi-disciplinary healthcare providers who care for this population.
METHODS: We recruited participants from Western/Central Pennsylvania, comprised of females with epilepsy ages 18-26 or parents of children with epilepsy ages 12-26. Healthcare providers who participated in the study were recruited nationally from disciplines of pediatric epilepsy, adult epilepsy, women's neurology, and adolescent medicine. We held three series of meetings to create the online materials from July to August 2021.
RESULTS: Five adolescent and young adult females with epilepsy (ages 18-26, median age 22) and two parents of children with epilepsy were recruited and participated in meetings. The physician group was comprised of two adolescent medicine physicians, one adult neurologist with a specialization in women's neurology, one adult epileptologist, and one pediatric epileptologist. All participants were female. Several sets of meetings were held, which involved the creation of an empathy map to evaluate the needs and desires of our participants, topic list development, and specific content and formatting recommendations. After these meetings, content was created for the online materials and published on the Center for Young Women's Health (CYWH) website.
CONCLUSION: Our team utilized co-production with a diverse group of partners to create educational materials that met the interests of adolescent and young adult females with epilepsy. This is a structured and reproducible methodology that could inform future educational intervention development in epilepsy. - ArticleKaradeniz Z, Aynacıoğlu AŞ, Bilir A, Tuna MY.Med Hypotheses. 2020 Jan;134:109420.Metformin, a drug widely used in the treatment of type II diabetes mellitus (T2DM), has been the focus of interest as a potential therapeutic agent for certain types of malignancies, including gynaecological cancers [i.e. endometrial cancer (EC)]. Although the exact mechanism behind the potential anticancer activity of metformin is still not completely understood, certain studies have suggested that different effects on cell functions, such as inhibition of cell migration, apoptosis and tumor cell proliferation, are involved in its preventive and therapeutic effects in certain types of malignancies, including EC. In contrast, midkine (MK), a heparin-binding growth factor and cytokine, which induces carcinogenesis and chemoresistance, promotes the development and progression of many malignant tumours by increasing diverse cell functions such as cell proliferation, cell survival and antiapoptotic activities via mainly the activation of phosphatidyl inositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. The same pathways are also subject to certain therapeutic effects of metformin, although this cytokine and this drug have some different mechanism of action pathways as well. Taken together, MK and metformin appear to have opposite effects in various biological processes such as apoptosis, cell proliferation, cell survival, cell migration, and angiogenesis. On the other hand, MK activates PI3K and MAPK cell signal pathways, whereas metformin inhibits these two pathways. It seems likely that almost all the pathways and cell functions, which play important roles in malignancies, are inhibited by metformin and activated by MK. Given the opposite relationship between the actions of metformin and MK, we hypothesize that metformin may act like a novel MK inhibitor in some malignancies. We also discuss the possible relationship between metformin and MK in the context of EC, the most common gynecological cancer worldwide, which incidence is rising rapidly, in parallel with the increase in obesity, T2DM and insulin resistance. In this respect, the therapeutic use of metformin may improve the survival of EC or other cancers, via inhibiting or overcoming the unwanted effects of MK in carcinogenesis.
- ArticleSong Z, Li K, Li K.Fish Shellfish Immunol. 2024 Mar;146:109420.The impact of carbonate alkalinity in saline-alkaline water on aquatic organisms, particularly Penaeus vannamei, a significant species in aquaculture, remains a critical area of study. To elucidate the acute response mechanisms of P. vannamei to elevated carbonate alkalinity environments, we utilized 16S rRNA gene and transcriptome sequencing technologies to analyze intestinal bacteria and gene expressions within various tissues. Our investigation revealed notable changes in specific intestinal bacterial OTUs, whose abundances varied preceding the overall bacterial community, indicating the sensitivity to carbonate alkalinity exposure. These shifts are accompanied by a simplification in bacterial networks and alterations in pathogenic OTUs, notably Aeromonas OTU. Concurrently, gene expression variations were observed across the hepatopancreas, gills, muscles, and intestines, with decreasing numbers of DEGs in the mentioned order. Annotation of these DEGs revealed enrichments in pathways related to transport, catabolism, immune responses, circulatory functions, and lipid metabolism. Notably, correlations between specific intestinal bacterial OTUs and gene expression shifts were identified across these tissues. Several OTUs, attributed to Rhizobiales, Saccharimonadales, Acidovora, and Aeromona, exhibited a correlation with DEGs in all four tissues, primarily associated with amino acid metabolism, signal transduction, and transport and catabolism pathways. Our study provides comprehensive insights into the dynamic responses of P. vannamei to elevated carbonate alkalinity stress. These findings contribute crucial knowledge for effective P. vannamei cultivation in saline-alkaline water, advancing our understanding in this field.
- ArticlePerkins JS.J Environ Manage. 2019 Nov 01;249:109420.As in other semi-arid savannah systems of the world characterised by highly mobile and/or migratory ungulates, Botswana's rangelands are experiencing increased fragmentation due to expanding human activities and increasing human wildlife conflict. Climate change scenarios show Botswana becoming hotter and drier with mega droughts, heat waves and more intense and spatially confined rainfall events. The Botswana Government has reacted by providing artificial water points (AWPs) in the Protected Areas and surrounding Wildlife Management Areas (WMAs), in part to compensate for the lack of access to historical sources due to fences and human expansion. Blanket provision of AWPs will disrupt the existing mobility and migratory strategies of the key ungulates that is basic to their survival and their ability to adapt to climate change. Botswana's burgeoning elephant population has already effectively re-connected the drier Kalahari System to the Northern System by breaching fences in the region. The key recommendations from the past are used to reinforce the need for ecosystem management for resilience at the landscape level via migratory corridors through shared landscapes, made possible by a renewed focus on Community Based Natural Resource Management and Payments for Ecosystem Services. The events that have occurred over the last 50 years are used to illustrate the dangers of managing at the wrong 'localised' spatial and temporal scale and failing to address the key factors of mobility and inequity that characterise the ecological and socio-economic systems, respectively.
- ArticleLi Z, Hu Y, Li Q.Radiother Oncol. 2023 01;178:109420.
- ArticleHavekes R, Heckman PRA, Wams EJ, Stasiukonyte N, Meerlo P, Eisel ULM.Cell Signal. 2019 Dec;64:109420.Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairments. The classical symptoms of the disease include gradual deterioration of memory and language. Epidemiological studies indicate that around 25-40% of AD patients have sleep-wake cycle disturbances. Importantly, a series of studies suggested that the relationship between AD and sleep disturbance may be complex and bidirectional. Indeed, accumulation of the extracellular neuronal protein amyloid-beta (Aβ) leads to altered sleep-wake behavior in both mice and humans. At the same time, disturbances of the normal sleep-wake cycle may facilitate AD pathogenesis. This paper will review the mechanisms underlying this potential interrelated connection including locus coeruleus damage, reductions in orexin neurotransmission, alterations in melatonin levels, and elevated cytokine levels. In addition, we will also highlight how both the development of AD and sleep disturbances lead to changes in intracellular signaling pathways involved in regulating neuronal plasticity and connectivity, particularly extremes in cofilin phosphorylation. Finally, current pharmacological and nonpharmacological therapeutic approaches will be discussed.
- ArticleYin Z, Mao Y, Zhang N, Su Y, Zhu J, Tong H, Zhang H.Biomed Pharmacother. 2019 Nov;119:109420.BACKGROUND: Over-expression of Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) in cancer cells has been reported in the context of several tumors (including ovarian cancer) and is associated with poor prognosis. The aim of this study was to construct a fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) and investigate its antitumor activity against ovarian cancer cells, bothin vitro and in vivo.
METHODS: A fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) eukaryotic expression vector was constructed and ROR1-IgG antibody was expressed in CHO cells. The characteristics of ROR1-IgG were investigated by ELISA, SPR, Western blotting, FACS and fluorescence staining analyses. CCK8 and wound healing assays were performed to determine inhibition and migration capacity of ovarian cancer cells after treatment with ROR1-IgGin vitro. Further, the antitumor activity of ROR1-IgG was assessed in vivo using tumor-mice xenograft model.
RESULTS: The results showed that ROR1-IgG could specifically bind to ROR1-positive cells (HO8910 and A2780) with a high affinity. Functional studies revealed that ROR1-IgG inhibited the malignant behavior of ROR1-positive cells (HO8910 and A2780) in a time- and dose-dependent manner. These effects were not observed in ROR1-negative lose386 cells. The tumor inhibition rates following treatment with low, medium, and high concentrations of ROR1-IgG were approximately 47.72%, 53.79%, and 60.51%, respectively. In addition, the expression of Bcl-2 was obviously reduced while that of Bax was distinctly elevated in xenografts.
CONCLUSIONS: Collectively, our findings suggest that ROR1-IgG may be a novel therapeutic agent for patients with ROR1-positive ovarian cancer. - ArticleZhang N, Yang G, Zhang W, Wang W, Zhou Z, Zhang H, Xu L, Chen Y.Eur J Radiol. 2021 Jan;134:109420.OBJECTIVES: To develop a fully automatic multiview shape constraint framework for comprehensive coronary artery calcium scores (CACS) quantification via deep learning on nonenhanced cardiac CT images.
METHODS: In this retrospective single-centre study, a multi-task deep learning framework was proposed to detect and quantify coronary artery calcification from CT images collected between October 2018 and March 2019. A total of 232 non-contrast cardiac-gated CT scans were retrieved and studied (80 % for model training and 20 % for testing). CACS results of testing datasets (n = 46), including Agatston score, calcium volume score, calcium mass score, were calculated fully automatically and manually at total and vessel-specific levels, respectively.
RESULTS: No significant differences were found in CACS quantification obtained using automatic or manual methods at total and vessel-specific levels (Agatston score: automatic 535.3 vs. manual 542.0, P = 0.993; calcium volume score: automatic 454.2 vs. manual 460.6, P = 0.990; calcium mass score: automatic 128.9 vs. manual 129.5, P = 0.992). Compared to the ground truth, the number of calcified vessels can be accurate recognized automatically (total: automatic 107 vs. manual 102, P = 0.125; left main artery: automatic 15 vs. manual 14, P = 1.000 ; left ascending artery: automatic 37 vs. manual 37, P = 1.000; left circumflex artery: automatic 22 vs. manual 20, P = 0.625; right coronary artery: automatic 33 vs. manual 31, P = 0.500). At the patient's level, there was no statistic difference existed in the classification of Agatston scoring (P = 0.317) and the number of calcified vessels (P = 0.102) between the automatic and manual results.
CONCLUSIONS: The proposed framework can achieve reliable and comprehensive quantification for the CACS, including the calcified extent and distribution indicators at both total and vessel-specific levels. - ArticleCharest H, Doualla-Bell F, Cantin R, Murphy DG, Lemieux L, Brenner B, Hardy I, Moisi D, Lo E, Baril JG, Wainberg MA, Roger M, Tremblay C.PLoS One. 2014;9(10):e109420.BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naïve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011.
METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%)], nucleoside [NRTI (from 78% to 37%) and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%)] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004).
CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant variants. - ArticleZelenka L, Pägelow D, Krüger C, Seele J, Ebner F, Rausch S, Rohde M, Lehnardt S, van Vorst K, Fulde M.J Neurosci Methods. 2022 Jan 15;366:109420.BACKGROUND: The crosstalk and reactivity of the cell type glia, especially microglia and astrocytes, have progressively gathered research attention in understanding proper brain function regulated by the innate immune response. Therefore, methods to isolate highly viable and pure glia for the analysis on a cell-specific level are indispensable.
NEW METHOD: We modified previously established techniques: Animal numbers were reduced by multiple microglial harvests from the same mixed glial culture, thereby maximizing microglial yields following the principles of the 3Rs (replacement, reduction, and refinement). We optimized Magnetic-activated cell sorting (MACS®) of microglia and astrocytes by applying cultivated primary glial cell suspensions instead of directly sorting dissociated single cell suspension.
RESULTS: We generated highly viable and pure microglia and astrocytes derived from a single mixed culture with a purity of ~99%, as confirmed by FACS analysis. Field emission scanning electron microscopy (FESEM) demonstrated integrity of the MACS-purified glial cells. Tumor necrosis factor (TNF) and Interleukin-10 (IL-10) ELISA confirmed pro- and anti-inflammatory responses to be functional in purified glia, but significantly weakened compared to non-purified cells, further highlighting the importance of cellular crosstalk for proper immune activation.
COMPARISON WITH EXISTING METHOD(S): Unlike previous studies that either isolated a single type of glia or displayed a substantial proportion of contamination with other cell types, we achieved isolation of both microglia and astrocytes at an increased purity (99-100%).
CONCLUSIONS: We have created an optimized protocol for the efficient purification of both primary microglia and astrocytes. Our results clearly demonstrate the importance of purity in glial cell cultivation in order to examine immune responses, which particularly holds true for astrocytes. We propose the novel protocol as a tool to investigate the cell type-specific crosstalk between microglia and astrocytes in the frame of CNS diseases. - ArticleAzmi YA, Renaldo J, Budiyanto T, Putri KTC, Mardihusodo HR.Int J Surg Case Rep. 2024 Mar;116:109420.INTRODUCTION AND IMPORTANCE: Penile fracture is a relatively uncommon condition that most commonly results from blunt trauma during sexual intercourse, forced flexion, masturbation, or rolling over. However, other causes are also possible. It is a catastrophic illness to the patient's organic and psychological health.
CASE PRESENTATION: We report a case of a 43-year-old male patient who sustained a penile fracture due to the presence of a toothbrush implant. No urethral injury was documented. The patient underwent surgical repair, and one month post-surgery, exhibited no deformity and had a normal sexual and voiding function.
CLINICAL DISCUSSION: Penile fracture is most commonly caused by blunt trauma during sexual intercourse. While it has not been documented in the literature, penile implants may increase the incidence of penile fractures. Clinical examination and urethrography confirmed the absence of urethral injury. In cases where a penile fracture is suspected, the only management is surgical exploration. This approach has resulted in the lowest rate of negative long-term sequelae and does not negatively impact the patient's psychological well-being.
CONCLUSION: Penile fracture is a rare but serious condition that can result from the presence of an unstandardized implant. It is not close to the incidence of penile fracture for unstandardized prosthesis as even the standardized implant can get fracture when counter to high velocity. To avoid functional and morphological abnormalities, surgical exploration is recommended as the primary course of treatment.