bluuebunny/crossref_metadata_2025 huggingface dataset:
CircRNAs and their regulatory roles in cancers
Authors: Tao Mei , Zheng Ming , Xu Yanhua , Ma Shuo , Zhang Weiwei , Ju Shaoqing
Published: August 2021

Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It’s particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.
Small airway function in Finnish COVID-19 survivors
Authors: Lindahl Anna , Reijula Jere , Malmberg Leo Pekka , Aro Miia , Vasankari Tuula , Mäkelä Mika Juhani
Published: August 2021

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.
Metal-based nanoparticles, sensors, and their multifaceted application in food packaging
Authors: Kumar Antul , Choudhary Anuj , Kaur Harmanjot , Mehta Sahil , Husen Azamal
Published: August 2021

Due to the global rise of the human population, one of the top-most challenges for poor and developing nations is to use the food produces safely and sustainably. In this regard, the storage of surplus food (and derived products) without loss of freshness, nutrient stability, shelf life, and their parallel efficient utilization will surely boost the food production sector. One of the best technologies that have emerged within the last twenty years with applications in the packaging of food and industrial materials is the use of green mode-based synthesized nanoparticles (NPs). These NPs are stable, advantageous as well as eco-friendly. Over the several years, numerous publications have confirmed that these NPs exert antibacterial, antioxidant, and antifungal activity against a plethora of pathogens. The storage in metal-based NPs (M-NPs) does not hamper the food properties and packaging efficiency. Additionally, these M-NPs help in the improvement of properties including freshness indicators, mechanical properties, antibacterial and water vapor permeability during food packaging. As a result, the nano-technological application facilitates a simple, alternate, interactive as well as reliable technology. It even provides positive feedback to food industries and packaging markets. Taken together, the current review paper is an attempt to highlight the M-NPs for prominent applications of antimicrobial properties, nanosensors, and food packaging of food items. Additionally, some comparative reports associated with M-NPs mechanism of action, risks, toxicity, and overall future perspectives have also been made.
Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain
Authors: Stephens Kimberly E. , Zhou Weiqiang , Renfro Zachary , Ji Zhicheng , Ji Hongkai , Guan Yun , Taverna Sean D.
Published: August 2021

Background

Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms.

Methods

To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund’s adjuvant (CFA) in rats.

Results

Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models.

Conclusions

Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.
Inflammatory resolution and vascular barrier restoration after retinal ischemia reperfusion injury
Authors: Abcouwer Steven F. , Shanmugam Sumathi , Muthusamy Arivalagan , Lin Cheng-mao , Kong Dejuan , Hager Heather , Liu Xuwen , Antonetti David A.
Published: August 2021

Background

Several retinal pathologies exhibit both inflammation and breakdown of the inner blood-retinal barrier (iBRB) resulting in vascular permeability, suggesting that treatments that trigger resolution of inflammation may also promote iBRB restoration.

Methods

Using the mouse retinal ischemia-reperfusion (IR) injury model, we followed the time course of neurodegeneration, inflammation, and iBRB disruption and repair to examine the relationship between resolution of inflammation and iBRB restoration and to determine if minocycline, a tetracycline derivative shown to reverse microglial activation, can hasten these processes.

Results

A 90-min ischemic insult followed by reperfusion in the retina induced cell apoptosis and inner retina thinning that progressed for approximately 2 weeks. IR increased vascular permeability within hours, which resolved between 3 and 4 weeks after injury. Increased vascular permeability coincided with alteration and loss of endothelial cell tight junction (TJ) protein content and disorganization of TJ protein complexes. Shunting of blood flow away from leaky vessels and dropout of leaky capillaries were eliminated as possible mechanisms for restoring the iBRB. Repletion of TJ protein contents occurred within 2 days after injury, long before restoration of the iBRB. In contrast, the eventual re-organization of TJ complexes at the cell border coincided with restoration of the barrier. A robust inflammatory response was evident a 1 day after IR and progressed to resolution over the 4-week time course. The inflammatory response included a rapid and transient infiltration of granulocytes and Ly6C+ classical inflammatory monocytes, a slow accumulation of Ly6Cneg monocyte/macrophages, and activation, proliferation, and mobilization of resident microglia. Extravasation of the majority of CD45+ leukocytes occurred from the superficial plexus. The presence of monocyte/macrophages and increased numbers of microglia were sustained until the iBRB was eventually restored. Intervention with minocycline to reverse microglial activation at 1 week after injury promoted early restoration of the iBRB coinciding with decreased expression of mRNAs for the microglial M1 markers TNF-α, IL-1β, and Ptgs2 (Cox-2) and increased expression of secreted serine protease inhibitor Serpina3n mRNA.

Conclusions

These results suggest that iBRB restoration occurs as TJ complexes are reorganized and that resolution of inflammation and restoration of the iBRB following retinal IR injury are functionally linked.
Experiences and perception towards reproductive health education among secondary school teachers in South India
Authors: Joseph Nitin , Mahato Vaibhav , Pandey Akhil , Mishra Shikha , Prakash Garima , Gandhi Rishika
Published: August 2021

Background

Reproductive health education (RHE) is an important component of school curricula. It helps students in the decision-making process regarding several issues concerning reproductive health. However delivering RHE at schools is a difficult task for the teachers.

Methods

This study was conducted to assess the experiences and perceptions towards reproductive health education (RHE) among 236 secondary school teachers in January 2019. Data were collected using a self-administered questionnaire.

Results

Only 21 (8.9%) were trained in RHE. Majority [179 (75.8%)] identified cultural barriers as the major challenge involved in its implementation. 95 (40.3%) teachers felt that the provision of sexual education as a part of RHE will promote pre-marital sexual activity among the students. Of the total, 185 (78.4%) had average while 51 (21.6%) participants had a good perception towards RHE. It was taught in only 3 (16.7%) out of the 18 schools surveyed. Only 11 (4.7%) participants felt that the availability of teaching aids to conduct RHE classes at their schools was adequate. Hardly 14 (5.9%) teachers had taken RHE classes for students. Among the rest, 135 (60.8%) expressed their willingness to take RHE classes with appropriate training. In multi variable analysis, participants aged ≤ 40 years (p = 0.031), those belonging to nuclear families (p = 0.013), and those who had taken classes in RHE (p = 0.037) had significantly good perception level towards RHE.

Conclusions

Teachers therefore need to be trained and given more opportunities to take RHE sessions which will help improve their perception towards RHE. Schools need to be better equipped with resources and various perceived barriers need to be overcome before RHE can be successfully implemented.
Serum biochemistry and haematology in wild and captive bearded seals (Erignathus barbatus) from Svalbard, Norway
Authors: Tryland Morten , Lydersen Christian , Kovacs Kit Maureen , Rafter Espen , Thoresen Stein Istre
Published: August 2021

Background

Health assessment of seals in captivity include haematology and serum biochemistry measurements. Because such parameters differ between species, it is crucial to have species-specific reference values for the interpretation of clinical samples. Furthermore, differences in nutrition and environment, life cycles as well as seasonal/annual cycles and varying physiological conditions can potentially affect serum chemistry and haematology parameters. Blood samples from four captive adult bearded seals (initially caught as pups in Svalbard, Norway, now held at Polaria, an Arctic experience centre in Tromsø, Norway) collected over a 16-month period were analysed for haematology (n = 22) and serum chemistry (n = 25) parameters. Serum chemistry analyses were also conducted on blood samples from 74 wild bearded seals (1995–2007) collected from Svalbard, Norway.

Results

We found higher activity of creatine kinase (CK) and higher concentrations of cortisol in the wild animals when compared to the captive seals, probably reflecting the physical restraint and concomitant stress induced during sampling. For the captive bearded seals, we did not find marked differences in haematology or serum chemistry parameters throughout the different seasons of sampling.

Conclusions

This study presents haematology and serum chemistry reference values for captive and wild bearded seals. Comparing physiological parameters for captive seals with wild seals indicated that having wild-caught bearded seals under the conditions offered at Polaria for several years did not markedly affect physiological parameters of the animals, and that training may have helped to alleviate stress associated with blood sampling and veterinary inspection.
MEN1 silencing aggravates tumorigenic potential of AR-independent prostate cancer cells through nuclear translocation and activation of JunD and β-catenin
Authors: Luo Yakun , Vlaeminck-Guillem Virginie , Baron Silvère , Dallel Sarah , Zhang Chang Xian , Le Romancer Muriel
Published: August 2021

Background

Recent studies highlighted the increased frequency of AR-low or -negative prostate cancers (PCas) and the importance of AR-independent mechanisms in driving metastatic castration-resistant PCa (mCRPC) development and progression. Several previous studies have highlighted the involvement of the MEN1 gene in PCa. In the current study, we focused on its role specifically in AR-independent PCa cells.

Methods

Cell tumorigenic features were evaluated by proliferation assay, foci formation, colony formation in soft agar, wound healing assay and xenograft experiments in mice. Quantitative RT-PCR, Western blot and immunostaining were performed to determine the expression of different factors in human PCa lines. Different ChIP-qPCR-based assays were carried out to dissect the action of JunD and β-catenin.

Results

We found that MEN1 silencing in AR-independent cell lines, DU145 and PC3, resulted in an increase in anchorage independence and cell migration, accompanied by sustained MYC expression. By searching for factors known to positively regulate MYC expression and play a relevant role in PCa development and progression, we uncovered that MEN1-KD triggered the nuclear translocation of JunD and β-catenin. ChIP and 3C analyses further demonstrated that MEN1-KD led to, on the one hand, augmented binding of JunD to the MYC 5′ enhancer and increased formation of loop structure, and on the other hand, increased binding of β-catenin to the MYC promoter. Moreover, the expression of several molecular markers of EMT, including E-cadherin, BMI1, Twist1 and HIF-1α, was altered in MEN1-KD DU145 and PC3 cells. In addition, analyses using cultured cells and PC3-GFP xenografts in mice demonstrated that JunD and β-catenin are necessary for the altered tumorigenic potential triggered by MEN1 inactivation in AR-independent PCa cells. Finally, we observed a significant negative clinical correlation between MEN1 and CTNNB1 mRNA expression in primary PCa and mCRPC datasets.

Conclusions

Our current work highlights an unrecognized oncosuppressive role for menin specifically in AR-independent PCa cells, through the activation of JunD and β-catenin pathways.
Accessory enzymes of hypercellulolytic Penicillium funiculosum facilitate complete saccharification of sugarcane bagasse
Authors: Ogunyewo Olusola A. , Upadhyay Pooja , Rajacharya Girish H. , Okereke Omoaruemike E. , Faas Laura , Gómez Leonardo D. , McQueen-Mason Simon J. , Yazdani Syed Shams
Published: August 2021

Background

Sugarcane bagasse (SCB) is an abundant feedstock for second-generation bioethanol production. This complex biomass requires an array of carbohydrate active enzymes (CAZymes), mostly from filamentous fungi, for its deconstruction to monomeric sugars for the production of value-added fuels and chemicals. In this study, we evaluated the repertoire of proteins in the secretome of a catabolite repressor-deficient strain of Penicillium funiculosum, PfMig188, in response to SCB induction and examined their role in the saccharification of SCB.

Results

A systematic approach was developed for the cultivation of the fungus with the aim of producing and understanding arrays of enzymes tailored for saccharification of SCB. To achieve this, the fungus was grown in media supplemented with different concentrations of pretreated SCB (0–45 g/L). The profile of secreted proteins was characterized by enzyme activity assays and liquid chromatography–tandem mass spectrometry (LC–MS/MS). A total of 280 proteins were identified in the secretome of PfMig188, 46% of them being clearly identified as CAZymes. Modulation of the cultivation media with SCB up to 15 g/L led to sequential enhancement in the secretion of hemicellulases and cell wall-modifying enzymes, including endo-β-1,3(4)-glucanase (GH16), endo-α-1,3-glucanase (GH71), xylanase (GH30), β-xylosidase (GH5), β-1,3-galactosidase (GH43) and cutinase (CE5). There was ~ 122% and 60% increases in β-xylosidase and cutinase activities, respectively. There was also a 36% increase in activities towards mixed-linked glucans. Induction of these enzymes in the secretome improved the saccharification performance to 98% (~ 20% increase over control), suggesting their synergy with core cellulases in accessing the recalcitrant region of SCB.

Conclusion

Our findings provide an insight into the enzyme system of PfMig188 for degradation of complex biomass such as SCB and highlight the importance of adding SCB to the culture medium to optimize the secretion of enzymes specific for the saccharification of sugarcane bagasse.
Optimized DNA-based identification of Toxocara spp. eggs in soil and sand samples
Authors: Jarosz Wojciech , Durant Jean-Francois , Irenge Leonid Mwana Wa Bene , Fogt-Wyrwas Renata , Mizgajska-Wiktor Hanna , Gala Jean-Luc
Published: August 2021

Background

Toxocara canisandToxocara catiare globally distributed roundworms and causative agents of human toxocariasis, via ingestion ofToxocaraeggs. Control ofToxocarainfections is constrained by a lack of sensitive methods for screening of animal faeces and environmental samples potentially contaminated byToxocaraeggs. In this work, a pre-analytical method for efficient extraction of DNA fromToxocaraeggs in environmental samples was set up using our previously validatedT.canis- andT.cati-specific quantitative real-time polymerase chain reaction (qPCR). For this purpose, the influence of different methods for egg lysis, DNA extraction and purification for removal of PCR inhibitors were assessed on environmental samples.

Methods

To select the best egg disruption method, six protocols were compared on pureT.canisegg suspensions, including enzymatic lysis and thermal or mechanical disruption. Based on the selected best method, an analytical workflow was set up to compare two DNA extraction methods (FastDNA™ SPIN Kit for Soil versus DNeasy®PowerMax®Soil Kit) with an optional dilution and/or clean-up (Agencourt®AMPure®) step. This workflow was evaluated on 10-g soil and 10-g sand samples spiked with egg suspensions ofT.canis(tenfold dilutions of 104eggs in triplicate). The capacity of the different methods, used alone or in combination, to increase the ratio of positive tests was assessed. The resulting optimal workflow for processing spiked soil samples was then tested on environmental soil samples and compared with the conventional flotation-centrifugation and microscopic examination ofToxocaraeggs.

Results

The most effective DNA extraction method forToxocaraeggs in soil samples consisted in the combination of mechanical lysis of eggs using beads, followed by DNA extraction with the DNeasy®PowerMax®Soil Kit, and completed with an additional DNA clean-up step with AMPure®beads and a sample DNA dilution (1:10). This workflow exhibited a limit of detection of 4 and 46T.caniseggs in 10-g sand and 10-g soil samples, respectively.

Conclusions

The pre-analytical flow process developed here combined with qPCR represents an improved, potentially automatable, and cost-effective method for the surveillance ofToxocaracontamination in the environment.

Graphical Abstract
Dirofilaria immitis and Dirofilaria repens in mosquitoes from Corsica Island, France
Authors: Younes Laidoudi , Barré-Cardi Hélène , Bedjaoui Samia , Ayhan Nazli , Varloud Marie , Mediannikov Oleg , Otranto Domenico , Davoust Bernard
Published: August 2021

Background

Dirofilaria immitis and Dirofilaria repens are the main causative agents of heartworm disease and subcutaneous dirofilariasis in domestic and wild canids, respectively. Both pathogens have zoonotic potential and are transmitted by mosquitoes. The present study aimed to determine the transmission period, prevalence and diversity of Dirofilaria spp. vectors from endemic areas of Corsica (France).

Methods

A monthly point data model based on average temperature recorded by four meteorological stations during 2017 was used to calculate the Dirofilaria transmission period. From June to September 2017, female mosquitoes (n = 1802) were captured using Biogents® Sentinel 2 traps lured with carbon dioxide and BG-Lure™ or octanol. Mosquitoes were identified to species level, pooled accordingly, and screened using multiplex real-time qPCR to detect D. immitis and D. repens.

Results

The monthly point data model showed the possible transmission of Dirofilaria spp. from the third week in May to the last week in October in the studied area. Mosquitoes were identified as Ochlerotatus caspius (n = 1432), Aedes albopictus (n = 199), Culex pipiens sensu lato (n = 165) and Aedes vexans (n = 6) and were grouped into 109 pools (from 1 to 27 specimens, mean 11.4 ± 0.7), of which 16 scored positive for Dirofilaria spp. (i.e., n = 13; estimated infection rate [EIR] = 1.1% for D. immitis and n = 3; EIR = 0.2% for D. repens). Specifically, 6 (i.e., EIR = 3.8%) of 15 pools of Ae. albopictus were positive for D. immitis, 2 of 14 of Cx. pipiens s.l. were positive for D. immitis and D. repens, respectively, and 8 of 77 pools of Oc. caspius were positive for D. immitis (i.e., n = 6; EIR = 0.4%) and D. repens (i.e., 2; EIR = 0.1%). The highest mosquito infection rate was recorded in July (EIR = 2.5%), then in June (EIR = 1.3%) and September (EIR = 0.6%).

Conclusions

The data suggest that both Dirofilaria species are endemic and occur possibly in sympatry in the studied area in Corsica, highlighting the need to implement preventive chemoprophylaxis and vector control strategies to reduce the risk of these filarioids in dog and human populations.

Graphical Abstract
Wolbachia prevalence in the vector species Culex pipiens and Culex torrentium in a Sindbis virus-endemic region of Sweden
Authors: Bergman Alexander , Hesson Jenny C.
Published: August 2021

Background

Wolbachia pipientis are endosymbiotic bacteria present in a large proportion of terrestrial arthropods. The species is known to sometimes affect the ability of its host to transmit vector-borne pathogens. Central Sweden is endemic for Sindbis virus (SINV), where it is mainly transmitted by the vector species Culex pipiens and Culex torrentium, with the latter established as the main vector. In this study we investigated the Wolbachia prevalence in these two vector species in a region highly endemic for SINV.

Methods

Culex mosquitoes were collected using CDC light traps baited with carbon dioxide over 9 years at 50 collection sites across the River Dalälven floodplains in central Sweden. Mosquito genus was determined morphologically, while a molecular method was used for reliable species determination. The presence of Wolbachia was determined through PCR using general primers targeting the wsp gene and sequencing of selected samples.

Results

In total, 676 Cx. pipiens and 293 Cx. torrentium were tested for Wolbachia. The prevalence of Wolbachia in Cx. pipiens was 97% (95% CI 94.8–97.6%), while only 0.7% (95% CI 0.19–2.45%) in Cx. torrentium. The two Cx. torrentium mosquitoes that were infected with Wolbachia carried different types of the bacteria.

Conclusions

The main vector of SINV in the investigated endemic region, Cx. torrentium, was seldom infected with Wolbachia, while it was highly prevalent in the secondary vector, Cx. pipiens. The presence of Wolbachia could potentially have an impact on the vector competence of these two species. Furthermore, the detection of Wolbachia in Cx. torrentium could indicate horizontal transmission of the endosymbiont between arthropods of different species.

Graphical abstract
The mechanism of Annexin A1 to modulate TRPV1 and nociception in dorsal root ganglion neurons
Authors: Zhang Yufen , Ma Sehui , Ke Xiao , Yi Yao , Yu Hongyan , Yu Dian , Li Qiang , Shang You , Lu Youming , Pei Lei
Published: August 2021

Background

Annexin A1 (ANXA1) exerts anti-nociceptive effect through ANXA1 receptor formyl peptide receptor 2 (FPR2/ALX (receptor for lipoxin A4), FPR2) at the dorsal root ganglia (DRG) level. However, the mechanisms remain elucidated. By using radiant heat, hot/cold plate, tail flick, von Frey, and Randall-Selitto tests to detect nociception in intact and chemical (capsaicin, menthol, mustard oil, formalin or CFA) injected AnxA1 conditional knockout (AnxA1−/−) mice, applying calcium imaging and patch clamp recordings in cultured DRG neurons to measure neuronal excitability, conducting immunofluorescence and western blotting to detect the protein levels of TRPV1, FPR2 and its downstream molecules, and performing double immunofluorescence and co-immunoprecipitation to investigate the interaction between Calmodulin (CaM) and TRPV1; we aim to uncover the molecular and cellular mechanisms of ANXA1’s role in antinociception.

Results

AnxA1−/− mice exhibited significant sensitivity to noxious heat (mean ± SD, 6.2 ± 1.0 s vs. 9.9 ± 1.6 s in Hargreaves test; 13.6 ± 1.5 s vs. 19.0 ± 1.9 s in hot plate test; n = 8; P < 0.001), capsaicin (101.0 ± 15.3 vs. 76.2 ± 10.9; n = 8; P < 0.01), formalin (early phase: 169.5 ± 32.8 s vs. 76.0 ± 21.9 s; n = 8; P < 0.05; late phase: 444.6 ± 40.1 s vs. 320.4 ± 33.6 s; n = 8; P < 0.01) and CFA (3.5 ± 0.8 s vs. 5.9 ± 1.4 s; n = 8; P < 0.01). In addition, we found significantly increased capsaicin induced Ca2+ response, TRPV1 currents and neuronal firing in AnxA1 deficient DRG neurons. Furthermore, ANXA1 mimic peptide Ac2-26 robustly increased intracellular Ca2+, inhibited TRPV1 current, activated PLCβ and promoted CaM-TRPV1 interaction. And these effects of Ac2-26 could be attenuated by FPR2 antagonist Boc2.

Conclusions

Selective deletion of AnxA1 in DRG neurons enhances TRPV1 sensitivity and deteriorates noxious heat or capsaicin induced nociception, while ANXA1 mimic peptide Ac2-26 desensitizes TRPV1 via FPR2 and the downstream PLCβ-Ca2+-CaM signal. This study may provide possible target for developing new analgesic drugs in inflammatory pain.
Quality of selected anti-retroviral medicines: Tanzania Mainland market as a case study
Authors: Mziray Sophia , Maganda Betty A. , Mwamwitwa Kissa , Fimbo Adam M. , Kisenge Seth , Sambu Gerald , Mwalwisi Yonah H. , Bitegeko Adonis , Alphonce Emmanuel , Khea Akida , Shewiyo Danstan H. , Kaale Eliangiringa
Published: August 2021

Background

Antiretroviral drugs (ARVs) have significantly reduced morbidity, mortality and improved the quality of life of people living with HIV infection. Poor quality ARVs may result in harmful consequences such as adverse drug reactions, treatment failure and development of drug resistant strains and sometimes death, which in turn may undermine the healthcare delivery system. To ensure optimal treatment outcomes, medicines quality control must be undertaken regularly. This study was aimed at evaluating the quality of ARVs circulating on the Tanzania Mainland market.

Methods

This was a survey study. ARVs samples were collected in 20 regions of Tanzania Mainland, between 2012 and 2018. All sampled ARVs were subjected to screening testing using the Global Pharma Health Fund® Mini-Lab kits. Sampled ARV’s that failed screening test or yielded doubtful results and 10 % (10 %) of all that complied with the screening test requirements were selected for full quality control testing. Quality control testing was conducted at the Tanzania Medicines and Medical Devices Authority (TMDA) laboratory a World Health Organisation prequalified. Samples collected from the medicine distribution outlets were also, subjected to product information review.

Results

A total of 2,630 samples were collected, of which 83.7 % (2200/2630) were from port of entry (POEs). All sampled ARVs were screened and conformed to the specifications, except of the fixed dose combination (FDC) lopinavir/ritonavir 0.27 % (7/2630) and lamivudine/zidovudine/nevirapine 0.27 % (7/2630) that failed the disintegration test. Out of the 100 samples selected for full quality control testing, 3 % of them failed to comply with the specifications, of which FDC stavudine/lamivudine/nevirapine failed disintegration and assay tests 2 % (2/100) and 1 % (1/100), respectively. Samples failing the assay test had low content of stavudine (86.6 %) versus specification limits (90 -110 %). Out of the 430 samples which were subjected to product information review, 25.6 % (110/430) failed to comply with the TMDA packaging and labelling requirements.

Conclusions

The quality of majority of ARVs circulating on the Tanzania Mainland market was good, even so, significant deficiencies on labelling and packaging were observed. These results call for continuous monitoring of quality of medicines circulating on the Tanzania Mainland market.
Joint effusion, anteroposterior stability, muscle strength and degree of patellofemoral osteoarthritis significantly impact outcome following revision ACL reconstruction
Authors: Andrä Kathleen , Kayaalp Enes , Prill Robert , Irlenbusch Lars , Liesaus Eckehard , Trommer Tilo , Ullmann Peter , Becker Roland
Published: August 2021

Purpose: Effusion, impaired muscle function and knee instability are considered as some of the most important factors effecting outcome following anterior cruciate ligament reconstruction (ACL-R) but the impact on revision ACL-R remains unclear. It was hypothesized that these factors will significantly worsen clinical outcome following revision ACL-R.

Methods

Seventy knees (13 female and 57 male) were followed retrospectively after revision ACL-R at a mean follow-up of 47.8 ± 20.7 months. Clinical examination was based on the International Knee Documentation Evaluation Form-2000 (IKDC), Tegner activity scale. Instrumented measurement of anterior tibial translation was performed using the Rolimeter® (DJO Global, Freiburg, Germany). Bilateral circumference of the thigh was measured 10 and 20 cm proximal to the medial joint space. Cartilage was assessed according to Outerbridge classification during both primary and revision ACL-R.

Results

Tegner activity scale decreased significantly from 7.8 ± 1.4 points at primary ACL-R to 7 ± 1.8 points at revision ACL-R, and 5.8 ± 1.7 points at the time of follow up (p < 0.001). Joint effusion (r = − 0.47, p < 0.01) and side to side differences in single leg hop test (r = − 0.48, p < 0.1) significantly correlated with inferior outcome. Cartilage lesions were found in 67% of the patients at the time of revision ACL-R compared to 38% at the time of primary ACL-R. According to the IKDC classification A was graded in three patients (4.3%), B in 35 (50%), C in 29 (41.4%) and D in three (4.3%). Joint effusion was measured in 35% of patients at the time of follow-up. Degeneration at the patellofemoral compartment of > grad 2 was responsible for IKDC grade C and D (p = 0.035). Instrumented anteroposterior site-to-site difference of ≥3 mm showed significant impact on clinical outcome (p < 0.019).

Conclusion

The study has shown that chronic effusion, quadriceps dysfunction, cartilage lesions especially at the patellofemoral compartment and side to side difference in anteroposterior stability significantly influences patient outcome after revision ACL-R. These factors require special attention when predicting patient’s outcome.

Level of evidence

Level-IV, case-controlled study.
Multimodal phantoms for clinical PET/MRI
Authors: Lennie Eve , Tsoumpas Charalampos , Sourbron Steven
Published: August 2021

Phantoms are commonly used throughout medical imaging and medical physics for a multitude of applications, the designs of which vary between modalities and clinical or research requirements. Within positron emission tomography (PET) and nuclear medicine, phantoms have a well-established role in the validation of imaging protocols so as to reduce the administration of radioisotope to volunteers. Similarly, phantoms are used within magnetic resonance imaging (MRI) to perform quality assurance on clinical scanners, and gel-based phantoms have a longstanding use within the MRI research community as tissue equivalent phantoms. In recent years, combined PET/MRI scanners for simultaneous acquisition have entered both research and clinical use. This review explores the designs and applications of phantom work within the field of simultaneous acquisition PET/MRI as published over the period of a decade. Common themes in the design, manufacture and materials used within phantoms are identified and the solutions they provided to research in PET/MRI are summarised. Finally, the challenges remaining in creating multimodal phantoms for use with simultaneous acquisition PET/MRI are discussed. No phantoms currently exist commercially that have been designed and optimised for simultaneous PET/MRI acquisition. Subsequently, commercially available PET and nuclear medicine phantoms are often utilised, with CT-based attenuation maps substituted for MR-based attenuation maps due to the lack of MR visibility in phantom housing. Tissue equivalent and anthropomorphic phantoms are often developed by research groups in-house and provide customisable alternatives to overcome barriers such as MR-based attenuation correction, or to address specific areas of study such as motion correction. Further work to characterise materials and manufacture methods used in phantom design would facilitate the ability to reproduce phantoms across sites.
Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report
Authors: Jimbo Hikari , Horimoto Yoshiya , Okazaki Misato , Ishizuka Yumiko , Kido Hidenori , Saito Mitsue
Published: August 2021

Background

Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.

Case presentation

A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.

Conclusions

The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.
Effect of uric acid-lowering therapy on renal function in patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Maruyama Yukio , Kumagai Takanori , Sugano Naoki , Yoshida Shigetaka , Ichida Kimiyoshi , Uchida Shunya
Published: August 2021

Background

Whether uric acid (UA)-lowering therapy (ULT) is effective in reducing the progression of renal dysfunction in patients with chronic kidney disease (CKD) remains controversial. Since several advances have been made in therapies for hyperuricemia, including novel xanthine oxidoreductase (XOR) inhibitors, we conducted a systematic review to clarify the effectiveness of ULT in preserving renal function among CKD patients.

Methods

In this systematic review, the MEDLINE database was searched up to June 2019. We included complete randomized controlled trials comparing renal events between adult non-dialyzed CKD patients, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, with and without ULTs. Changes in eGFR were expressed as the mean difference (MD). The incidence of dichotomous outcomes was expressed as a risk ratio. This review was performed using the predefined protocol published in PROSPERO (CRD 42019140346).

Results

Eleven studies with 4277 CKD patients were included. Drugs used in the intervention groups of all studies were XOR inhibitors (allopurinol, febuxostat or topiroxostat). Although patients with ULT tended to show superior preservation of eGFR as compared to those without ULT, no significant differences were identified (MD, 2.52; 95% confidence interval, − 0.15 to 5.18). In subgroup analysis, the use of allopurinol was associated with superior preservation of eGFR, whereas the newer XOR inhibitors, febuxostat and topiroxostat, showed no significant effects on eGFR changes. Neither incidence of end-stage kidney disease nor treatment-emergent adverse events differed significantly between groups.

Conclusions

The present systematic review and meta-analysis suggested that CKD patients with ULT tend to show superior eGFR preservation as compared to patients without ULT, but further studies are needed to verify the renoprotective effects of ULT.
LC-ESI-tandem MS and in silico ADMET analysis of polyphenols from Rhus coriaria L. and Micromeria fruticosa (L.) Druce ssp. brachycalyx P. H. Davis
Authors: Taskin Duygu , Ozdemir Mucahit , Yalcin Bahattin
Published: August 2021

Background

Micromeria fruticosa (L.) Druce ssp. brachycalyx P. H. Davis and Rhus coriaria L., which are Lamiaceae species, are used both as spices in food and medicinally. Lamiaceae species are known to contain high amounts of polyphenols. In this study, liquid chromatography–quadrupole time-of-flight–tandem mass spectrometry (LC-QTOF-MS/MS) was used for analysis of polyphenols in the plants. Under gradient elution with using 0.1% aqueous acetic acid solution and acetonitrile mobile phases, an Agilent Poroshell C18 reversed phase column was used for the simultaneous determination of 18 polyphenols, and separation was performed in 30 min. Pharmacokinetic properties of these polyphenols such as drug-like and toxicity were estimated using open-source software, pkCSM and SwissADME.

Results

These compounds were determined to represent different classes of polyphenols, including phenolic acids, flavonoids, coumarin and tannins. ADMET predictions of polyphenols indicated that these compounds are easily absorbed and do not have toxic effects.

Conclusion

While the Rhus coriaria L. includes anthocyanidins, tannins, phenolic acid and flavonoids, the Micromeria fruticosa (L.) Druce ssp. brachycalyx P. H. Davis has phenolic acid, coumarin and flavonoids, according to these results. In silico ADME/Tox predictions revealed that these bioactive components are to be drug-like and non-mutagenic. These data are supportive for future analysis that can lead to their therapeutic use of the plants, suggesting that this species may be used as a natural medicinal source in the future after detailed analysis tests.

Graphical abstract
Specificity and off-target effects of AAV8-TBG viral vectors for the manipulation of hepatocellular gene expression in mice
Authors: Kiourtis Christos , Wilczynska Ania , Nixon Colin , Clark William , May Stephanie , Bird Thomas G.
Published: August 2021

Mice are a widely used pre-clinical model system in large part due to their potential for genetic manipulation. The ability to manipulate gene expression in specific cells under temporal control is a powerful experimental tool. The liver is central to metabolic homeostasis and a site of many diseases, making the targeting of hepatocytes attractive. Adeno-associated virus 8 (AAV8) vectors are valuable instruments for the manipulation of hepatocellular gene expression. However, their off-target effects in mice have not been thoroughly explored. Here, we sought to identify the short-term off-target effects of AAV8 administration in mice. To do this, we injected C57BL/6J wild-type mice with either recombinant AAV8 vectors expressing Cre recombinase or control AAV8 vectors and characterised the changes in general health and in liver physiology, histology and transcriptomics compared to uninjected controls. We observed an acute and transient trend for reduction in homeostatic liver proliferation together with induction of the DNA damage marker γH2AX following AAV8 administration. The latter was enhanced upon Cre recombinase expression by the vector. Furthermore, we observed transcriptional changes in genes involved in circadian rhythm and response to infection. Notably, there were no additional transcriptomic changes upon expression of Cre recombinase by the AAV8 vector. Overall, there was no evidence of liver injury, and only mild T-cell infiltration was observed 14 days following AAV8 infection. These data advance the technique of hepatocellular genome editing through Cre-Lox recombination using Cre expressing AAV vectors, demonstrating their minimal effects on murine physiology and highlight the more subtle off target effects of these systems.
Análise do desfecho perinatal em mulheres com near miss materno: estudo de caso controle
Authors: Arantes Brenda Magalhães , Arantes Karen Magalhães , Freitas Efigênia Aparecida Maciel de , Limongi Jean Ezequiel
Published: August 2021

Objetivo: verificar a associação entre mulheres com critérios para near miss materno e o desfecho perinatal adverso. Métodos: realizado um estudo caso-controle, de abordagem quantitativo-exploratória por meio do levantamento de prontuários de mulheres internadas no ano de 2017, em um hospital público brasileiro de nível terciário. Resultados: Na análise bivariada, as condições obstétricas graves estiveram associadas aos óbitos perinatais, à prematuridade, ao baixo peso ao nascer, ao Apgar < 7 no primeiro minuto de vida, à necessidade de procedimentos ao nascer e à internação em Unidade de Terapia Intensiva. Após regressão logística, permaneceram associados a prematuridade e o encaminhamento à Unidade de Terapia Intensiva. Conclusões: o manejo adequado, em conformidade com as boas práticas de atenção ao parto e ao nascimento e as boas condições prévias de saúde reduzem o impacto na morbimortalidade materna e infantil.
Βουλκανισμός ελαστομερών παρουσία θερμοπλαστικών
Authors: Μαρέδης Νίκος
Published: August 2021

ΣΤΟΧΟΣ ΤΗΣ ΔΙΑΤΡΙΒΗΣ ΗΤΑΝ Η ΔΗΜΙΟΥΡΓΙΑ ΥΛΙΚΩΝ ΜΕ ΑΥΞΗΜΕΝΗ ΕΝΕΡΓΕΙΑ ΔΙΑΣΧΙΣΗΣ ΚΑΙ ΤΑΣΗ ΕΝΔΟΤΙΚΟΤΗΤΑΣ ΣΕ ΤΡΙΒΗ.ΔΗΜΙΟΥΡΓΗΘΗΚΑΝ ΜΗΧΑΝΙΚΑ ΜΙΓΜΑΤΑ ΑΠΟ ΤΟ ΕΛΑΣΤΟΜΕΡΕΣ SBR,ΤΥΧΑΙΟ ΣΥΜΠΟΛΥΜΕΡΕΣ ΤΩΝ ΣΤΥΡΕΝΙΟΥ-ΒΟΥΤΑΔΙΕΝΙΟΥ ΜΕ 22.5% ΣΕ ΣΤΥΡΕΝΙΟ ΚΑΙ ΑΠΟ ΤΟ ΗΜΙΚΡΥΣΤΑΛΛΙΚΟ ΠΟΛΥΜΕΡΕΣ LLDPE,ΤΥΧΑΙΟ ΣΥΜΠΟΛΥΜΕΡΕΣ ΤΩΝ ΓΡΑΜΜΙΚΟΥ ΧΑΜΗΛΗΣ ΠΥΚΝΟΤΗΤΑΣ ΠΟΛΥΑΙΘΥΛΕΝΙΟΥ-ΕΠΤΕΝΙΟΥ.ΑΚΟΛΟΥΘΗΣΕ ΒΟΥΛΚΑΝΙΣΜΟΣ ΜΕ ΘΕΙΟ.ΤΟ LLDPE ΑΠΕΤΕΛΕΣΕ ΤΗΝ ΣΚΛΗΡΗ ΦΑΣΗ ΤΟΥ ΜΙΓΜΑΤΟΣ ΚΑΙ ΗΤΑΝ ΔΙΑΣΚΟΡΠΙΣΜΕΝΟ ΣΕ ΜΟΡΦΗ ΣΤΑΓΟΝΩΝ ΣΤΗ ΜΑΛΑΚΗ ΦΑΣΗ ΤΟΥ ΕΛΑΣΤΟΜΕΡΟΥΣ ΚΑΙ ΜΕΧΡΙ 0.5 ΚΛΑΣΜΑ ΟΓΚΟΥ ΤΟΥ ,ΟΠΟΥ ΑΡΧΙΣΕ Η ΑΝΑΣΤΡΟΦΗ ΤΗΣ ΦΑΣΗΣ,ΕΝΩ ΠΕΡΑΝ ΑΥΤΗΣ ΠΑΡΑΤΗΡΗΘΗΚΕ ΣΥΝΕΧΕΙΑ ΤΩΝ ΦΑΣΕΩΝ,ΟΠΩΣ ΑΠΟΔΟΘΗΚΕ ΑΠΟ ΤΟ ΜΟΝΤΕΛΟ ΠΡΟΒΛΕΨΗΣ ΤΟΥ ΜΕΤΡΟΥ ΕΛΑΣΤΙΚΟΤΗΤΑΣ BUDIANSKY, ΚΑΙ ΕΠΙΒΕΒΑΙΩΘΗΚΕ ΑΠΟ ΤΗΝ ΗΛΕΚΤΡΟΝΙΚΗ ΜΙΚΡΟΣΚΟΠΙΑ ΣΑΡΩΣΗΣ.Η ΠΑΡΟΥΣΙΑ ΤΟΥ LLDPE ΒΕΛΤΙΩΣΕ ΣΗΜΑΝΤΙΚΑ ΤΗΝ ΕΝΕΡΓΕΙΑ ΔΙΑΣΧΙΣΗΣ ΚΑΙ ΤΗΝ ΤΑΣΗ ΕΝΔΟΤΙΚΟΤΗΤΑΣ ΣΕ ΤΡΙΒΗ ΜΕ ΒΕΛΤΙΣΤΗ ΑΠΟΔΟΣΗ ΤΗΝ 0.2 ΚΛΑΣΜΑ ΟΓΚΟΥ ΣΕ LLDPE.ΣΤΗ ΣΥΓΚΕΝΤΡΩΣΗ ΑΥΤΗ ΟΙ ΕΛΑΣΤΙΚΕΣ ΙΔΙΟΤΗΤΕΣ ΠΑΡΟΥΣΙΑΣΑΝ ΒΕΛΤΙΩΣΗ(ΤΑΣΗ ΘΡΑΥΣΗΣ,ΕΠΙΜΗΚΥΝΣΗ ΘΡΑΥΣΗΣ), ΕΝΩ ΑΙΣΘΗΤΗ ΗΤΑΝ Η ΒΕΛΤΙΩΣΗ ΚΑΙ ΤΗΣ ΑΝΤΙΣΠΑΣΗΣ ΤΩΝ ΜΙΓΜΑΤΩΝ ΣΤΟ ΟΛΟΝ.
Ο έλεγχος της νευροψυχικής εξελίξεως κατά Gesell επί δυστροφικών και τροφίμων βρεφοκομείου
Authors: Μπαρούτσου-Τσέλιου Ελβίρα
Published: August 2021

Στόχος της έρευνας είναι η επίδραση της σωματικής δυστροφίας και του περιβάλοντος στην ψυχοκινητική ανάπτυξη του παιδιού. Μέθοδοι: τρείς ομάδες παιδιών ηλικίας από 4 εβδομάδες εώς 3 έτη. Ι. 108 ευτροφικά παιδιά (μάρτυρες). ΙΙ. 74 δυστροφικα, ΙΙΙ. 70 από το βρεφοκομείο Αθηνών. Εκτίμηση ψυχοκινητικής ανάπτυξης: Gesell's test. Ιδιοτυπίες ανάπτυξης στα παιδιά της έρευνας στις ονάδες Ι και ΙΙ. Σε 31 παιδιά με δυστροφία (41,9%) ανευρίσκεται μεγαλύτερη καθυστέρηση στην αδρή κίνηση ανάλογη με το βαθμό της δυστροφίας, Η καθυστέρηση στους υπόλοιπους τρείς τομείς συμπεριφοράς (προσαρμογή, γλώσσα, προσωποκοινωνική αντίδραση) είναι μικρότερη και δεν σχετίζεται απόλυτα με το βαθμό δυστροφίας. Σε κλινική βελτίωση της δυστροφίας η αδρή κίνηση αποκαθίσταται τελευταία. Στα παιδιά του βρεφοκομείου μετά την ηλικία των 4 μηνών η ψυχοκινητική ανάπτυξη του παιδιού καθυστερεί περισσότερο στους τρεις τομείς της νευροψυχικής εξέλιξης και λιγότερο στην αδρή κίνηση. Η διαφορά αυτή γίνεται περισσότερο εμφανής μετά το πρώτο έτος της ζωής. Σαφώς η δυστροφία θίγει περισσότερο τις στατικές λειτουργίες του οργανισμού. Η έλλειψη ερεθισμάτων και αγάπης θίγει περισσότερο την ψυχική εξέλιξη του παιδιού.
Ο Λέων Α' και η εποχή του
Authors: Ελευθεριάδης Ευριπίδης-Ευθύμιος
Published: August 2021

Στο Α' μέρος παρουσιάζονται και αξιολογούνται οι πηγές της περιόδου, ιστοριογραφικά, νομικά, αγιολογικά κείμενα και νομίσματα. Εξετάζεται ο βίος και η σταδιοδρομία του Λέοντος μέχρι την ανάδειξή του σε αυτοκράτορα. Τα μεγάλα προβλήματα που είχε να αντιμετωπίσει η αυτοκρατορία του 4ου και 5ου αι. με τις επιδρομές και τη διείσδυση των "βαρβάρων" στο κράτος, η αποκατάσταση της ενότητας της εκκλησίας που είχε διασαλευτεί από τις αιρέσεις και τα μέτρα που πήρε ο Λέων για την οργάνωση του στρατού και τη διοίκηση της αυτοκρατορίας. Επίσης τα νομοθετικά μέτρα του αυτοκράτορα εναντίον Αρειανών και Εθνικών και γενικά για την προάσπιση της Ορθοδοξίας. Ακολουθεί η ανάλυση της πνευματικής φυσιογνωμίας του Βυζαντίου, ο ρόλος που διαδραμάτισαν θρησκευτικοί ηγέτες της εποχής και η αντιμετώπιση του μονοφυσιτισμού, που έθετε σε κίνδυνο την ενότητα της Εκκλησίαςκαι κατ' επέκταση της αυτοκρατορίας. Στο Β' μέρος εξετάζεται η εκστρατεία κατά των Βανδάλων που παρά την συντριπτική υπεροχή των Βυζαντινών κατέληξε σε τραγική αποτυχία. Εξετάζεται ακόμη η πολιτική του προς το δυτικό τμήμα της αυτοκρατορίας και η ρύθμιση της διαδοχής στο τμήμα αυτό από τον Λέοντα. Αναλύονται οι διπλωματικές σχέσεις του με τους γείτονες λαούς της αυτοκρατορίας του, οι οποίες γενικά υπήρξαν ομαλές. Στο Γ' μέρος αναφέρεται στην εξόντωση του Άσπαρ. την δίωξη των Γότθων από την Κωνσταντινούπολη, την απομάκρυνσή τους από τον κρατικό μηχανισμό και την αντικατάστασή τους από τους Ισαύρους. Εξετάζονται τα μέτρα που πήρε ο Λέων Α' για την αντιμετώπιση του σεισμού της Αντιόχειας το 458 και της πυρκαϊάς στην Κων/πολη το 465. Η μη απόκτηση γιού από τον Λέοντα προκάλεσε πρόβλημα σχετικά με τη διαδοχή του.