Consuming harmful amounts of alcohol is considered a contributing factor in over 200 diseases. Heavy episodic drinking is a particularly risky drinking pattern, with possible consequences such as acute alcohol intoxication, injuries and violence. GEDA 2014/2015-EHIS defines heavy episodic drinking as the consumption of six or more alcoholic beverages on one occasion at least once per month. 24.9% of women and 42.6% of men show this drinking pattern at least once per month. Regular heavy episodic drinking is most common among 18- to 29-year-olds. The prevalence of heavy episodic drinking among highly educated women  and men (aged over 45) is lower than it is among those with lower levels of education. The prevention of harmful levels of alcohol consumption requires measures including social and environmental interventions as well as targeting the individual behaviour which are focused on young adults as well as the diverse drinking patterns seen among groups with different levels of education. Alcohol is a potentially addictive psychoactive substance. Consuming harmful levels of alcohol is considered a contributing factor to over 200 diseases; globally, it is among the five key risk factors for disease, impairment and death . In addiHeavy episodic drinking is a drinking pattern which poses a particularly high risk to an individual’s health and can lead to acute alcohol intoxication, injuries and violence. On the long-term, it can lead to addiction and damages to multiple organs . Such daData holder: Robert Koch InstituteAims: To provide reliable information about the population’s health status, health-related behaviour and health care in Germany, with the possibility of a European comparisonMethod: Questionnaires completed on paper or onlinePopulation: People aged 18 years and above with permanent residency in GermanySampling: Registry office sample; randomly selected individuals from 301 communities in Germany were invited to participateParticipants: 24,016 people Response rate: 26.9%Study period: November 2014 - July 2015Data protection: This study was undertaken in strict accordance with the data protection regulations set out in the German Federal Data Protection Act and was approved by the German Federal Commissioner for Data Protection and Freedom of Information. Participation in the study was voluntary. The participants were fully informed about the study’s aims and content, and about data protection. All participants provided written informed consent.www.geda-studie.deMore information in German is available at Heavy episodic drinking (HED) is defined as the intake of 60 g or more of pure alcohol at a single occasion at least once per month . This isGerman Health Update: New data for Germany and Europe in issue 1/2017 of the Journal of Health Monitoring.The analyses are based on the data received from 23,704 respondents aged 18 and above  who gave valid answers on heavy episodic drinking. Calculations were carried out using a weighting factor that corrects for deviations within the sample from the German population (as of 31 December 2014) with regard to gender, age, district type and education. The district type accounts for the degree of urbanisation and reflects the regional distribution in Germany. The International Standard Classification of Education (ISCED) was used to ensure that the responses provided on educational levels were comparable [48.8% of women and 29.7% of men responded that they had never, or at least not during the past 12 months, drunk six or more alcoholic beverages on a single occasion. 24.9% of women and 42.6% of men  said theconsumption of risky amounts, the figures for heavy episodic drinking reveal an inverse education gradient. These results are in line with other surveys that indicate the higher prevalence of risky drinking patterns, such as heavy episodic drinking, in socially disadvantaged groups [Across all age groups, there are fewer highly educated women who drink six or more alcoholic beverages in a single session than women with a lower or medium level of education. For men in the 18-44 age group, no such association with education appears to exist. For men over 45, the prevalence of heavy episodic drinking among those highly educated is lower than among the group with a lower level of education. Compared to figures for the d groups . Moreoved groups . As alcod groups , preventCompared to the German average, the prevalence of heavy episodic drinking among men is significantly higher in North Rhine-Westphalia and significantly lower in Baden-Württemberg. For women, variance between federal states and in comparison with the German average is low. The prevalence of heavy episodic drinking among women is lowest in Brandenburg (20.7%) and significantly higher in North Rhine-Westphalia (27.5%) .http://www.kenn-dein-limit.info/) run by Germany’s Federal Centre for Health Education (BZgA) is targeted specifically at adolescents and young adults. For adults, the campaign ‘Kenn dein Limit – Bewusst genießen, im Limit bleiben’ (Respect your limits – enjoy responsibly and stay below the limit) provides information and recommendations for low-risk drinking (https://www.kenn-dein-limit.de/).The GEDA 2014/2015-EHIS figures are thereby notably higher than those surveyed in the German Health Interview and Examination Survey for Adults (DEGS1)  and GEDA25% of women and 43% of men engage in heavy episodic drinking at least once per month.Among 18- to 29-year-olds, more than half of all men and over a third of all women drink six or more units on one occasion at least once per month.For those aged 65 or over, more than one third of men and around one fifth of women engage in heavy episodic drinking at least once per month.As a behavioural pattern, heavy episodic drinking is less frequent among highly educated women than among those with lower levels of education. In men, the same pattern is shown for those aged over 45.


The widespread use of nanotechnology has reached almost every sector in our daily lives and amazed the world by offering various potential applications in these sectors. The uprising wave of nanotechnology and its application are now prominent in the fields of chemistry and biomedicine, which are vital as these fields serve as a basis for the discovery of new molecules that may benefit humans. Nanotechnology contributed to the advancement of promising techniques either by the implementation of existing methods or by the establishment of new ones. Researchers in academia and industry sectors working in areas of biochemistry, chemical engineering, molecular biology, and genetics are likely to come across the advantages of applying nanobiotechnology tools in their studies. This profound technological advantage has brought many research laboratories to globally exchange ideas and promote intensive international scientific collaborations to further increase the level of understanding of applying nanotechnology to biological systems.This thematic issue aims to provide vital findings to support new research and innovations utilizing recent trends in nanobiotechnological processes to encourage the development of these converging technologies for a sustainable economic growth.The synthesis and the characterization of nanoscale biomaterials, the innovative applications of “smart nanoparticles”, and the technological/biological impact of nanoscale systems are just some of the areas of focus in the field known as nanobiotechnology . NanobioIn this thematic issue we invited many authors to contribute with manuscripts on novel concepts, ingenious designs, and promising applications in the field of nanobiotechnology. The submitted works were expected to feature innovative areas such as nanomaterials applied in biotechnology; nanoparticles used in environmental science and technology; nanosensors used in biosystems; nanomedicine in the context of biochemical engineering; micro- and nanofluidics; micro- and nano-electromechanical systems; nanoscience and nanotoxicology; nanotechnology applied in biology, medicine, food, environmental and agriculture sectors; environmental engineering and chemical engineering; nanoscale electrochemisty in biotechnology; computational nanochemistry in biotechnology; and life cycle assessment of nanobiotechnology.The works presented in this thematic issue covered topics related to new concepts and ideas pertaining to the design and development of nanobiotechnology. These works include “The role of deep eutectic solvents and carrageenan in synthesizing biocompatible anisotropic metal nanoparticles” . This reThe thematic issue also recorded a work on the topic of “Self-assembly of amino acids toward functional biomaterials” , where tSome other hot topics in the field of nanobiotechnology were also covered in the thematic issue. One of these topics is on the “Design and selection of peptides to block the SARS-CoV-2 receptor binding domain by molecular docking” . This reThe collection of comprehensive reviews and studies assembled in this thematic issue on nanobiotechnology trends provides useful and new scientific knowledge regarding the advancement of nanobiotechnology for science, technological, and engineering-related applications. A total of five high quality works were published within the thematic issue, with great support from researchers in various continents. The guest editors wish to express their gratitude to all the contributors, authors and reviewers, who have collectively ensured and maintained the standards of scientific quality within the works published. Finally, we also thank Dr. Wendy Patterson, Dr. Lasma Gailite, and Dr. Barbara Hissa for their support in the development of the “New Trends in Nanobiotechnology” thematic issue.


We aimed to explore the senescence-associated effects of lincRNA-p21 in 1-methyl-4-phenylpyridinium . The Telo TAGGG™ Telomerase PCR ELISA PLUS Kit was used to determine telomerase activity. Cellular viability was evaluated with the 3--2,5-diphenyl-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Western blot was performed to analyze β-catenin protein expression. Besides, oxidative stress was evaluated by J-aggregate-forming delocalized lipophilic cation, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine++ + iodide (JC-1) stain, fluorescence spectrophotometry, colorimetric assay, and malondialdehyde (MDA) formation.+ caused a distinct increase in the expression of LincRNA-p21 in SH-SY5Y cells. MPP+ induced cellular senescence with decreasing cellular proliferation and viability, increasing expression levels of senescence-associated makers such as genes p53 and p16, accompanied by significantly decreasing telomere length and telomerase activity. At the same time, these effects were abolished by silencing lincRNA-p21 with small interfering RNA (siRNA). On the contrary, β-catenin silencing contributes to reversing anti-senescent effects caused by lincRNA-p21 silencing. Moreover, modifying lincRNA-p21 exerted an anti-senescent influence depending on decreasing oxidant stress.This research demonstrated that MPP+, lincRNA-p21 might serve a role in the SH-SY5Y cell senescence by modulating the Wnt/β-catenin pathway, as well as increasing oxidant stress. Thus, trying to target lincRNA-p21 may have important therapeutic and practical implications for PD.Our study showed that in the treatment of MPP HoweverCurrent treatments focus on improving motor disorders rather than preventing the neurodegeneration of healthy dopaminergic neurons, leading to PD's continuous progression and irreversibility , 14. ConLincRNA-p21, which is related to cell proliferation, metabolism, and reprogramming, is considered a potential diagnostic marker of various diseases . StudiesThe Wnt/β-catenin pathway, which can be inhibited by lincRNA-p21, participates in several critical physiological and pathological processes of the central nervous system by regulating cell survival, proliferation, and differentiation , 20, 21.+) treated neuroblastoma SH-SY5Y cell line, which is one of the most classical PD models, as an invitro PD model in our study. MPP+ is an active metabolite of 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin commonly employed to create an in vitro PD model in human dopaminergic cell lines such as SH-SY5Y neuroblastoma cells [+ is transported into dopaminergic neurons by the dopamine transporter (DAT), resulting in suppression of mitochondrial complex I and adenosine triphosphate (ATP) synthesis and an increase in reactive oxygen species (ROS), which ultimately results in neurodegeneration [Given the high level of lincRNA-p21 expression in PD, the neuroprotective effects of Wnt/β-catenin, and recent studies that have demonstrated that lincRNA-p21 could inhibit β-catenin expression, we investigated the function and molecular processes behind lincRNA-p21 in the pathogenesis and development of PD. We chose a 1-methyl-4-phenylpyridinium   for 24 h as a PD model.SH-SY5Y were purchased from the American Type Culture Collection  and cultured in DMEM  supplemented with 10% FBS (Gibco) at 37°C. As previously described , SH-SY5Y2.2The viability of the cultured SH-SY5Y cell line was examined by MTT assay and LDH assay. For the MTT assay, MTT in PBS (Gibco) was added to each well of 96-flat-bottom plates for 4 h before SH-SY5Y harvesting. The absorbance of each well at 570 nm was recorded. For LDH assay, an LDH assay kit  was used to raise the detection level of LDH. According to the protocol, cell culture medium was collected and mixed with LDH reaction buffer for 0.5 h at 25°C. The absorbance was measured at 490 nm.2.3-∆∆Ct method was used to examine all the data.RT-qPCR was used to analyze the levels of target genes, including lincRNA-p21, p53, p16, and β-catenin. Briefly, total RNAs were isolated from the SH-SY5Y cell line using TRIzol reagent  and reverse-transcription into cDNA by the SuperScript cDNA Synthesis Kit (Invitrogen). RT-qPCR was then carried out with SYBR Premix Ex TaqTM (2×)  and a fluorescent quantitative PCR system (Applied Biosystems). Finally, the 22.4According to a previously known method, this study quantified the relative telomere length in SH-SY5Y with the qPCR methodology .2.5For quantitative analyses of telomerase activity, the telomeric repeat amplification protocol (TRAP) assay, in which telomerase reaction product is amplified by polymerase chain reaction (PCR), was performed using the Telo TAGGG PCR ELISA PLUS kit  according to the manufacturer's instructions.2.6RIPA buffer was used to extract total proteins. Proteins were separated on SDS-PAGE gels and transferred to PVDF membranes. Primary and secondary antibodies were as follows: β-catenin , β-actin , Wnt1 , and horseradish peroxidase-conjugated anti-rabbit secondary antibodies .2.7SiRNA-lincRNA-p21, Ad-Ctrl, Ad-lnc-p21, and siRNA-β-catenin were designed and synthesized. The SH-SY5Y cell line was transfected with siRNAs by Lipofectamine 2000 (Invitrogen).2.8After washing in PBS, the SH-SY5Y cell line was incubated with JC-1 . The JC-1 fluorescence was then measured with an ELISA plate reader.2.9Intracellular ROS of each group were assessed by 2,7-dichlorodihydrofluorescein diacetate . A fluorescence spectrophotometer was used to measure the fluorescence intensity of the cells.2.10SOD activity in the SH-SY5Y cell line was evaluated with the colorimetric assay kit . Briefly, proteins were isolated, and SOD activity was measured with the absorbance at 450nm.2.11The production of MDA was measured using an assay kit to evaluate lipid peroxidation. The SH-SY5Y cell line was incubated with MDA lysis buffer, and the supernatant was then added to thiobarbituric acid. At 532 nm, the absorbance of the samples was measured.2.12The mean and standard deviation were used to present the data. Differences between the two groups were analyzed with a T-test. The statistical significance of differences among more than two groups was determined by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. SPSS version 21.0  was used for all statistical analyses.33.1+ were measured and its functions in induced cellular senescence were investigated. Following MPP+ treatment, RT-qPCR analysis indicated a considerable increase in lincRNA-p21 expression . Furthermore, after MPP+ treatment, the viability of SH-SY5Y decreased significantly . The MPP+-treated group had significantly higher p53 and p16 levels than the controls . Finally, MPP+ treatment reduced telomere length and telomerase activity compared to the control cells .The lincRNA-p21 levels in the SH-SY5Y cell line subjected to MPP3.2+-induced SH-SY5Y were examined further by siRNA-mediated knockdown of endogenous lincRNA-p21. The RT-qPCR analysis confirmed that the level of lincRNA-p21 in SH-SY5Y cells was reduced following the transfection with a lincRNA-p21-specific siRNA . Cell viability was markedly higher in lincRNA-p21-knockdown cells exposed to MPP+ than in control siRNA-NT cells treated with MPP+ . In addition, the knockdown of lincRNA-p21 with siRNA significantly reduced p53 and p16, as well as distinctly increased telomere length and telomerase activity in MPP+-treated cells . By contrast, treatment of SH-SY5Y with a non-specific control siRNA (siRNA-NT) did not alleviate cellular senescence in the presence of MPP+.The senescence effects of lincRNA-p21 in MPP3.3+-treated group had lower levels of β-catenin protein . Besides, the knockdown of lincRNA-p21 increased β-catenin expression in the MPP+-treated SH-SY5Y cell line . To examine the relevance of these findings further, we silenced β-catenin using a specific siRNA. As expected, the SH-SY5Y cell line transfected with the siRNA-β-catenin had significantly lower expression levels of the β-catenin mRNA than those transfected with the control siRNA-NT . Furthermore, the aforementioned attenuating effects of lincRNA-p21 knockdown on MPP+-induced decreases cell viability, increases in p53 and p16 expression, accompanied by reductions in telomere length and telomerase activity. These effects were significantly reversed by silencing β-catenin .Previous studies revealed that lincRNA-p21 down-regulated β-catenin levels [3.44), MPP+ treatment reduced the mitochondrial transmembrane potential and activity of SOD, as well as increased the expression levels of ROS and MDA in SH-SY5Y cells. However, these effects were diminished by silencing lincRNA-p21. In addition, β-catenin silencing contributed to blocking the anti-senescence effects caused by lincRNA-p21 silencing.Recent findings have shown that Wnt/β-catenin is related to oxidative stress . As show+-induced cellular senescence was specifically caused by lincRNA-p21-mediated oxidative stress, we then attempted to investigate the impact of a well-known powerful antioxidant agent NAC on SH-SY5Y senescence in the presence of MPP+. NAC significantly decreased ROS generation in the presence of MPP+ . LincRNA-p21 was overexpressed after transfection with Ad-lnc-p21 in the SH-SY5Y cell line . NAC reversed the MPP+-induced decreases in cell viability, increases in p53 and p16 expression, as well as reductions in telomere length and telomerase activity of the SH-SY5Y cell line. Nevertheless, transfection of cells with Ad-lnc-p21 abolished these anti-senescence effects .To demonstrate that MPP4+ promoted cellular senescence, as demonstrated by decreases in cell viability, increases in p53 and p16 expression, as well as reductions in telomere length and telomerase activity in SH-SY5Y cells.Previous research regarding lincRNA-p21 focused mostly on its impact on cancer . However+ caused a distinct increase in the expression of LincRNA-p21 with decreasing cell viability, increasing expression levels of senescence-associated makers such as genes p53 and p16, accompanied by significantly decreasing telomere length and telomerase activity in SH-SY5Y cells. At the same time, these effects were abolished by silencing lincRNA-p21 with small interfering RNA (siRNA). The above findings suggested that lincRNA-p21 may play crucial functions in regulating neuronal cell senescence in PD and confirmed the results of increasing lincRNA-p21 from human brain specimens [As a transcription inhibitor, lincRNA-p21 triggers cell damage, senescence, and apoptosis . One stupecimens .+ could significantly down-regulated the expression level of β-catenin, while this effect could be abolished by knockdown of lincRNA-p21. By contrast, β-catenin silencing contributes to reversing anti-senescent effects caused by lincRNA-p21 silencing. The limitation is that we did not evaluate the Wnt level with a western blot. Similar to our study, Wei et al. reported that activation of the Wnt/β-catenin signaling pathway with exogenous Wnt1 could protect the SH-SY5Y cell line against 6-hydroxydopamine, which is another kind of in vitro PD model [Given the significance of cellular senescence on the development of PD, there is considerable interest in exploring the methods to target senescence for therapeutic purposes . A well-PD model . An earlPD model . Based o+ induced oxidative stress, as evidenced by reducing the mitochondrial transmembrane potential and SOD activity, as well as increasing the expression levels of ROS and MDA in SH-SY5Y cells. These oxidation effects could be mitigated by silencing lincRNA-p21. Consistent with our findings, Xu et al. found that lincRNA-p21 inhibits cell viability and promotes cell apoptosis in PD and Wang et al. demonstrated that reducing oxidative stress can improve PD [Cellular senescence is accompanied by enhanced oxidative stress, such as increased ROS production, increased oxidase activity, and decreased antioxidant enzyme activity , 31. Notprove PD , 35. Of There are some potential agents targeting the PD-involved pathway found, such as hydrogen sulfide, lithium, cannabidiol, and stem-cell-based therapies , 36-38.+, lincRNA-p21 might serve a role in the SH-SY5Y cell senescence by modulating the Wnt/β-catenin pathway, as well as increasing oxidant stress. Based on those results, down-regulating lincRNA-p21 expression to alleviate senescence in neuronal may be a helpful strategy in treating PD.In summary, we found that in the treatment of MPP+, lincRNA-p21 might serve a role in the SH-SY5Y cell senescence by modulating the Wnt/β-catenin pathway, as well as increasing oxidant stress. Thus, trying to target lincRNA-p21 may have important therapeutic and practical implications for PD.Our study showed that in the treatment of MPP


The results show that the addition of Mg2+ and Cu2+ charging agents can improve the electrophoretic deposition efficiency and coating adhesion of nano-TbF3 powders on sintered Nd-Fe-B magnets. The EPD efficiency increases by 116% with a relative content of Mg2+ as 3%, while it increases by 109% with a relative content of Cu2+ as 5%. Combining the Hamaker equation and diffusion electric double layer theory, the addition of Mg2+ and Cu2+ can change the zeta potential of charged particles, resulting in the improvement of EPD efficiency. The relative content of Mg2+ below 3% and Cu2+ below 5% can increase the thickness of the diffusion electric double layer, the excessive addition of a charging agent will compress the diffusion electric double layer, and thicker diffusion layer represents higher zeta potential. Furthermore, the addition of Mg2+ and Cu2+ charging agents greatly improves the coating adhesion, and the critical load for the cracking of the coating increases to 146.4 mN and 40.2 mN from 17.9 mN, respectively.In order to prepare nano-TbF3 coating with high quality on the surface of Nd-Fe-B magnets by electrophoretic deposition (EPD) more efficiently, Mg Howev4B phase ,4. Grain4B phase ,6.3, TbH3, DyF3 and DyH3 are mainly electrophoretically deposited in organic suspension [To prepare the diffusion source on the magnet surface, we can use different coating methods such as dipping , magnetrspension ,15,16,17spension . +), bases (OH−), adsorbed metal ions or adsorbed poly-electrolytes are used to obtain particle surfaces’ electrosteric stabilization for an effective EPD process [3 EPD suspension as a charging agent and found that PEI maintains its very strong cationic charge by protonation of the amine groups from the surrounding medium. Guan et al. [2O3 film on the magnet surface by EPD and used polyethylene imine (PEI) to improve the coating adhesion and EPD efficiency in an isopropanol suspension. Wang et al. [2 into TbF3 EPD suspension to improve the EPD efficiency and the coating adhesion. Cu2+ has also acted as a charging agent in the process of co-deposition to form copper–graphene composite films [2+ and Cu2+ charging agents on EPD efficiency and coating adhesion were systematically studied. In addition, the mechanism of action of Mg2+ and Cu2+ charging agents was analyzed with the theory of EPD and diffusion double layer from the perspective of deposition kinetics.The dissociation or ionization of surface groups on particles and the adsorption of surfactants are the most important mechanisms to obtain stable nonaqueous EPD suspension and a good EPD process . Chargin process . Das et  process  prepared process  added Pon et al.  preparedg et al.  added 5 te films . These s3 (900 nm) powder provided by GRIREM Advanced Materials Co., Ltd. , was used as the diffusion source. TbF3 powder and anhydrous ethanol were mixed into 8 g/L suspension, MgCl2 or CuCl2 with a mass of 1–10% relative to TbF3 was added and mechanical stirring was performed until MgCl2 or CuCl2 was completely dissolved; then, the ultrasonic was performed for 2 min until the suspension was uniform. Copper plate as anode and sample as cathode which were soaked in suspension, and TbF3 coating was obtained by EPD at 60 V voltage for 1–5 min. The deposited samples were then diffused under vacuum at 900 °C for 7 h, followed by tempering at 500 °C for 2 h.A commercial sintered Nd-Fe-B magnet provided by GRIREM Co., Ltd. was selected as the initial magnet. The magnet was wire cut into cuboids with sizes of 8 × 8× 7 mm (c-axis). Then, the magnet was polished with 600 mesh, 1000 mesh and 2000 mesh sandpaper until the surface of the sample was flat and smooth. Subsequently, the surface of the polished magnet sample was cleaned with conduct alkali washing, acid washing and anhydrous ethanol ultrasonic cleaning and dried for later use. Nano TbFζ potential of the suspension was tested by a Zeta potential tester . The acidity and alkalinity of the suspension were detected by precision pH test paper. Coating adhesion was tested by a micro-nano mechanical testing system .The magnetic properties of the samples were measured by a high temperature permanent magnet measuring instrument  and the microstructure of the coating was characterized by a scanning electron microscope . The coating elements were analyzed by ICP. The phases of the coating powders stripped from the surface of magnet were measured by XRD. The viscosity of the suspension was measured by a rotary rheometer . The 3 with different relative contents of Mg2+ (a) and Cu2+ (b). It was found that with the increase in the relative content of Mg2+, the EPD efficiency increased first and then decreased, reaching the highest value when the relative content of Mg2+ was 3%, with the efficiency improving 116% from 3.1 mg/(cm2/min) to 6.7 mg/(cm2/min). The voltage was used for ion migration when adding too much Mg2+, which resulted in EPD basically unable to occur. For Cu2+, the EPD efficiency also first increased and then decreased with the increase in the relative content of Cu2+. Unlike Mg2+, the EPD efficiency reached the highest when the relative content of Cu2+ was 5%, with the efficiency improving 109% from 3.1 mg/(cm2/min) to 6.47 mg/(cm2/min). EPD can continue to occur if Cu2+ is continuously increased, but the efficiency of EPD will decline rapidly. The reasons will be added later.2+ and Cu2+. 3 amount (a) and EPD rate (b) of nano-TbF3 at different times. It can be seen in 3 amount is proportional to the time in the EPD theory. It is also found in 2+ reduced more than that of the others, which indicates that some changes occur to reduce the EPD efficiency when adding Cu2+ to the EPD suspension. Relatedly, adding Mg2+ will not affect the EPD process.The EPD behavior with different time was studied by adding the best relative content of Mg2+ added and increased to 60 μm with 5% Cu2+ added. This also proves that the addition of Mg2+ and Cu2+ improves the EPD efficiency. 2+ and Cu2+ on the EPD efficiency from the perspective of kinetics, we first introduce the EPD Hamaker equation [In order to further study the effect of Mgequation :(1)m=ε0εm is the amount of EPD, ε0 is the dielectric constant of vacuum, εr is the dielectric constant of solution, η is the viscosity of EPD suspension, C is the particle concentration in EPD suspension, ζ is the zeta potential of charged particles, E is the applied electric field strength, L is the electrode spacing and t is the EPD time. In this paper, both the applied electric field’s strength and the distance between the electrodes were constant. EPD efficiency was calculated by dividing the EPD quantity by the EPD time. Therefore, the EPD efficiency at the same EPD time is inversely proportional to the η and ζ. Firstly, the effect of Mg2+ and Cu2+ on the viscosity of the EPD suspension was tested in order to study the kinetic reason of improving the EPD efficiency. The rotating rheometer tested the viscosity of suspension by shearing generated by a rotating motion, so we tested the viscosity with a shear rate of 0–1000 to enhance the accuracy of the test. 2+ and Cu2+ relative contents. It can be found that the viscosity of the EPD suspension increased with the increase in the shear rate (γ) because of the viscous resistance of the particles in the suspension, but the viscosity curves of different Mg2+ and Cu2+ relative contents were basically coincident. Since the average viscosity of the various concentrations was essentially consistent across the illustrations, it is clear that the addition of Mg2+ and Cu2+ had little impact on the EPD suspension’s viscosity.In the equation, 2+ and Cu2+ addition on the zeta potential of EPD suspension was investigated. 2+ (a) and Cu2+ (b). It can be seen that the zeta potential initially increased and then decreased with the change of Mg2+ and Cu2+ relative content, which is consistent with the change trend of EPD efficiency in 2+ and 5% Cu2+ compared with ζ potential. The effect of Mg2+ and Cu2+ on ζ potential was highly consistent with that on EPD efficiency. Therefore, we can confirm that the adding of Mg2+ and Cu2+ affected the efficiency of EPD by changing the zeta potential of the EPD suspension.Subsequently, the effect of Mg2+, or the higher zeta potential with a higher relative content of Cu2+ (such as 10%) than without Cu2+ but with a lower EPD rate than without Cu2+, we analyzed the coating elements. 2+ contained 0.71 wt.% Cu, while adding Mg2+ contained none. 2+ charging agents; it can be seen that the coating had a peak of copper and no peak of CuCl2, which indicates that Cu2+ in EPD suspension will be reduced to Cu under the electric field. In addition, Mg2+ can hardly be reduced to elemental because the discharge order is after H+, while Cu2+ is in front of H+.In order to explain the lower rate of later EPD with the addition of Cu2+ and reducing the content of positive charge in the EPD suspension. Additionally, the process of generating Cu is not conducive to the deposition of TbF3 on the surface of the magnet. This is also the reason for the uneven coating surface in This process reduces the EPD rate because of consuming Cu2+ and Cu2+ affect the zeta potential of the EPD suspension by adsorption. 3 particle. It can be seen in 2+ and Cu2+ was low, the surface charge of the ion was gradually saturated. The diffusion double layer gradually became thicker with the increase in Mg2+ and Cu2+ on the surface, and the zeta potential was also higher, so the EPD efficiency gradually increased. When EPD efficiency reached the highest value, the surface charge of the particles was saturated; as − in the suspension.According to the diffusion double layer theory , Mg2+ an2+ and Cu2+ were added, respectively, which indicates that the addition of Mg2+ and Cu2+ charging agents greatly improved the coating adhesion. 2+ added showed regular gully morphology with distributed micro-cracks compared with the coating without a charging agent, which is profit for the release of stress [2+ added exists aggregates on the surface, and shows finer gully morphology, which may be the reason that the coating adhesion was between without charging agents and with Mg2+ charging agents.Good coating adhesion can ensure the GBD result after EPD. To test it, we applied a linear normal load of transverse movement to the coating, and determined the coating adhesion according to the load when the coating cracked. f stress . As is s2+ and Cu2+ can improve the EPD efficiency and the adhesion of the coating, but it cannot be at the expense of deteriorating the magnetic properties after heat treatment. A high-temperature permanent magnet measuring instrument (NIM-500C) was used to measure the magnetic properties of the permanent magnetic materials at room temperature and high temperatures, respectively. An external field of ~3 T was initially applied to make the samples magnetized at full saturation. The remanence (Br), coercivity (Hcj) and maximum magnetic energy product (BH)max of the magnet were obtained by testing the demagnetization curve of the material. cj) of the original magnet was 19.3 kOe. With the first heat treatment process of 900 °C for 7 h, and the second heat treatment process of 500 °C for 2 h, the coercivity of the undeposited reference sample decreased to 18.1 kOe, while the coercivity of the EPD sample and EPD sample with Mg2+ and Cu2+ increased to 22.3 kOe, 22.2 kOe and 22.6 kOe, respectively. The remanence of all samples did not decrease. It indicates that the addition of Mg2+ and Cu2+ had no effect on the TbF3 coating GBD process. As an aside, the preparation of TbF3 coating containing copper has some development prospects, because Cu can promote GBD by widening the grain boundary [The addition of Mgboundary . 3 coating on the surface of the magnet was prepared with the addition of Mg2+ and Cu2+ in the EPD suspension, and the effects of Mg2+ and Cu2+ on EPD efficiency and coating adhesion were studied. The conclusions were as follows:(1)2+ and Cu2+ can improve the EPD efficiency. With 3% relative content of Mg2+ added, the efficiency improved 116% from 3.1 mg/(cm2/min) to 6.7 mg/(cm2/min). With 5% relative content of Cu2+ added, the efficiency improved 109% from 3.1 mg/(cm2/min) to 6.47 mg/(cm2/min).The addition of Mg(2)2+ and Cu2+ on the EPD efficiency from the perspective of kinetics was analyzed with the Hamaker equation and diffusion double layer theory; it was found that Mg2+ and Cu2+ influence the EPD efficiency by changing the zeta potential of charged particles, but not the viscosity of suspension. In addition, the diffusion electric double layer absorbs Mg2+ or Cu2+ to increase its thickness, which indicates higher zeta potential of TbF3 particles when the relative content of Mg2+ and Cu2+ is low. When the relative content reaches 3% and 5%, respectively, the diffusion electric double layer reaches saturation, and further addition of a charging agent will compress the diffusion electric double layer and reduce zeta potential. Furthermore, the reduction reaction of Cu2+ is the reason of the lower rate of later EPD when Cu2+ charging agents were added.The effect of Mg(3)2+ and Cu2+ charging agents greatly improve the coating adhesion; the critical load for the cracking of the coating increased to 146.4 mN and 40.2 mN from 17.9 mN, respectively. Furthermore, the addition of Mg2+ and Cu2+ has no bad effect on TbF3 coating GBD of the magnet.It was found that the addition of MgNano-TbF


Malnutrition is a rising global health issue associated with unfavorable outcomes of a variety of disorders. Currently, the prevalence and prognostic significance of malnutrition to patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remained largely unclear.A total of 705 patients diagnosed with ACS and CKD in the First Affiliated Hospital of Wenzhou Medical University between 2013 and 2021 were included in this retrospective cohort study. Malnutrition was assessed by the Controlling Nutritional Status (CONUT), the Geriatric Nutritional Risk Index (GNRI), and the Prognostic Nutritional Index (PNI), respectively. The relationships between malnutrition and all-cause mortality and major cardiovascular events (MACEs) were analyzed.r = 0.77 between GNRI and PNI, r = −0.72 between GNRI and CONUT, and r = −0.88 between PNI and CONUT, all p < 0.001). Compared with normal nutrition, malnutrition was independently associated with an increased risk for all-cause mortality : 2.69 to 19.49] and 17.56 [95% CI: 5.61 to 55.09] for the CONUT score, 2.18 [95% CI: 0.93 to 5.13] and 3.16 [95% CI: 1.28 to 7.79] for the GNRI, and 2.52 [95% CI: 1.62 to 3.94] and 3.46 [95% CI: 2.28 to 5.25] for the PNI score. p values were lower than 0.05 for all nutritional indexes, except for moderate GNRI p value = 0.075). As for MACEs, similar results were observed in the CONUT and PNI. All the risk scores could improve the predictive ability of the Global Registry of Acute Coronary Events (GRACE) risk score for both all-cause mortality and MACEs.During a median follow-up of 31 months, 153 (21.7%) patients died, and 165 (23.4%) had MACEs. The prevalence of malnutrition was 29.8, 80.6, and 89.8% for the PNI, CONUT, and GNRI, respectively. All the malnutrition indexes were correlated with each other (Malnutrition was common in patients with ACS and CKD regardless of the screening tools used, and was independently associated with all-cause mortality and MACEs. Malnutrition scores could facilitate risk stratification and prognosis assessment. MalnThe current guidelines recommend using the GRACE score to predict mortality and MACEs for ACS patients . Data frIn this study, we aimed to explore the prevalence and prognostic value of malnutrition in patients with ACS and CKD using different malnutrition screen tools.2.2.1.A total of 760 ACS patients were diagnosed as having CKD and underwent PCI, among them 7 were combined with lymphoma or leukemia, 32 showed missing data of ALB, total cholesterol, height, and weight, 16 lost to follow-up, and eventually 705 were included in this retrospective cohort study . This st2.2.2, including uremia. Uremia was defined as eGFR <15 mL/min per 1.73 m2 or receiving renal replacement therapy. The baseline SCr was measured at hospital admission. The glomerular filtration rate was calculated by serum creatinine level upon admission, according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)  . To avoi2.3.The nutritional status of the enrolled patients was analyzed based on the three easy-to-use scores that are effective to identify patients facing a high risk of malnutrition.As a screening tool for the nutritional condition of hospitalized patients, the Controlling Nutritional Status (CONUT)  consisteThe Geriatric Nutritional Risk Index (GNRI) was calculated using the following formula: 1.489*serum albumin (g/l) + 41.7*weight (kg) / ideal body weight (kg) . The ide3)  was obtained using the formula: 10*serum albumin (g/dl) + 0.005*total lymphocyte count (mm3) . A scoreVenous blood samples  were taken following an overnight fast at admission. To prevent variations due to measurement scale or location between laboratories, all the measurements were examined and standardized in one central laboratory.2.4.The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiovascular events (MACEs) consists of cardiovascular death, re-infarction, or ischemic stroke. Cardiovascular death was defined as any death from cardiovascular causes. Re-infarction was defined as an recurrent elevation of cardiac enzymes greater than the upper limit of the normal range with at least one of the following: (1) recurrent ischemic symptoms, (2) electrocardiograph changes implicating ischemia, (3) development of pathological Q waves, and (4) coronary thrombus proved by angiography. Ischemic stroke was defined as ischemic lesion demonstrated by the evidence of neurological dysfunction or clinically documented lesions on imaging. Outcome information was acquired from medical records or by telephone follow-up at 1 month and then every 6 months after discharge. All patients were followed up for at least 1 month unless they died within 1 month. Follow-up was continued from the date of admission to the date of death. If there were no endpoints happened, time at the last medical encounter in primary or secondary care was taken. The median follow-up time was 31 months (inter-quartile range: 17 to 53 months). The rate of lost follow-up was 2.1%.2.5.n (%). The groups were compared using the chi-square test, the student t-test, and the Mann–Whitney U test for categorical data, normally distributed continuous data, and skewed data, respectively. In order to determine the relationships between nutritional indices, c-reactive protein (CRP), and eGFR, Spearman (skewed variables) correlation analysis was employed. Venn diagram was used to show how the three nutritional indexes were related to the status of malnutrition.Continuous variables were expressed as the mean ± standard deviation if normally distributed or otherwise median with interquartile range (25th to 75th percentiles). Categorical variables were presented as p value less than 0.05 in the univariable Cox regression analyzes were chosen for the adjusted model. The following variables were selected as covariates for the adjusted model in the present research: age, sex, BMI, hypertension, diabetes, hyperlipidemia, prior myocardial infarction, prior PCI or CABG, type of ACS, Killip class ≥ II, serum creatinine, left ventricular eject fraction (LVEF) < 40%, multivessel disease, medications at discharge including beta-blockers, ACEI/ARBs and statins, and GRACE risk score. The possible nonlinear relationships between malnutrition scoring systems and outcomes were further analyzed on a continuous scale with restricted cubic spline (RCS) curves after adjusting the variables described above, with 3 nodes at the fixed percentiles of 25, 50, and 75% of the distribution of malnutrition scores.To show the distribution of events over time, Kaplan–Meier curves were created. Log-rank test was then used to compare groups with various nutritional statuses, followed by performing Cox proportional hazards regression analysis. Variables associated with known poor prognosis, clinical plausibility, or To assess the discrimination and reclassification performance of malnutrition scores, we combined the three scores with the GRACE score and calculated the C-statistic, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The C-statistics were compared by using the Delong test . The GRA3.3.1.2, and the median age was 73 years old. Most of them were combined with hypertension (77.45%) and about one-half of the patients had hyperlipidemia (51.63%). There are 67 dialysis patients, accounting for 9.5% of the total number. Among the 705 participants with ACS and CKD in this study, 442 (62.7%) had STEMI and 263 (37.3%) had NSTE-ACS. 528 (74.89%) of the patients were male, the median BMI was 23.64 kg/mPatients with malnutrition determined by any of the three malnutrition scores were older and were more likely to be female with lower BMI, higher CRP level, and higher GRACE risk scores than those with normal nutritional status. They also had worse clinical presentations, worse cardiac and renal functions, and were less likely to receive statins at discharge –S4.3.2.p value <0.01, as shown in r = 0.32; PNI: r = −0.31; GNRI: r = −0.28, all p < 0.01, 3.3.n = 88) cardiovascular deaths, 7.8% (n = 55) re-infractions, and 4.0% (n = 28) ischemic strokes.During a median follow-up of 31 months (inter-quartile range: 17 to 53 months), all-cause mortality occurred to 153 (21.7%) patients and MACEs occurred to 165 (23.4%) patients. The percentage (and number) of each cardiovascular event was as follows: 12.5% (p < 0.001), as demonstrated by the Kaplan–Meier analysis  in analysis . Regardlanalysis  or categanalysis , a worsep < 0.001). As for categorical variables, mild, moderate, and severe malnutrition defined by CONUT score were all independently associated with the all-cause mortality and MACEs , except for mild malnutrition with MACEs . As for PNI, moderate and severe malnutrition were both independently associated with increased risk of mortality and MACEs when compared with normal nutrition . As for GNRI, only the association between severe malnutrition and all-cause mortality was statistically significant .Moreover, the association between malnutrition degrees and each cardiovascular outcomes is shown in 3.4.p = 0.02; IDI: 0.024, p = 0.02). However, the CONUT showed a higher sensitivity than the PNI, which had was of a higher specificity than the CONUT for both outcomes .In Each of the three measures provided strong predictive value on the GRACE risk score for both 6-month all-cause mortality and MACEs risk prediction. The PNI showed the greatest additional value as it improved the C-statistics from 0.696 to 0.773 and from 0.653 to 0.710 for predicting mortality and MACEs, respectively. More detailed data about the incremental value are presented in 4.2. The addition of nutrition scores to the GRACE significantly enhanced the ability to predict all-cause mortality and MACEs. Accordingly, the current findings revealed that malnutrition were prevalent in patients with ACS and CKD, and that malnutrition was an independent risk factor for all-cause mortality and MACEs regardless of the screening tools used. The addition of malnutrition scores to the existing risk score could help in better identification of high-risk patients with ACS and CKD.To the best of our knowledge, this is the first study to report the prevalence and prognostic value of malnutrition among patients with ACS and CKD. Based on the three different malnutrition scores, the predicted prevalence of any degree malnutrition in patients with ACS and CKD varied from 29.8 to 89.8%. Depending on the scores used, the prevalence of moderate to severe malnutrition ranged from 29.8 to 80.4%. Even after adjusting age, sex, the GRACE score and other potential risk factors, malnutrition was still associated with unfavorable outcomes as predicted by any of these scores. Similar results were observed in subgroup analysis and the association between GNRI and MACEs was more pronounced in patients with BMI ≥ 25 kg/mThough some studies have demonstrated the benefits of invasive management of ACS in patients with CKD , 22, othSignificant correlations among the three different scores were found , but then = 58) and less representative CKD population, the last study  and the Science and Technology Planning Project of Wenzhou Science & Technology Bureau of Zhejiang Province of China (Y20160118).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Video gaming is an extremely popular leisure activity, with over two billion users worldwide .Nevertheless, excessive video game playing exposes to potential dangers. The WHO reminds us that “every gamer should be aware of the time spent on games, especially if their daily activities are affected, as well as any physical or psychological, social and health changes that could be attributed to gaming behaviour.”The aim of our study is to analyse the frequency of video game use, and to determine its relationship with psychological and social functioning and academic performance.A cross-sectional study was conducted in the child psychiatry department at Arrazi Hospital in Salé among adolescents aged between 10 and 17 years. For this, we used :A hetero-questionnaire on socio-demographic characteristics, reasons for gambling, type of gambling, satisfaction, self-esteem, ability to make friends and degree of social support, and school results , The DSM 5 criteria proposed in the appendix for the research and The K-SADSOur study was carried out on a sample of 57 adolescents aged between 10 and 17 years, with an average age of 13.47.There was a predominance of males: Boys: 87. ; Girls: 17.5Socio-demographic data54.4% reported having both real and virtual friends, 29.8% specified that all their friends are virtual, And 15.8% noted that they have no friendsAcademic decline was noted by the parents of 61.1% of adolescents Psychological functioning 68.4% reported low self-esteem, 31.6% reported being dissatisfied with their lives and 0.5% met the diagnostic criteria for video game addictionAll the adolescents are in school: Primary 26.3 , Middle school 59.6 , High school 14 % Social functioning and academic performanceOur study finds that problematic video game use is related to male gender, low academic performance, difficulties with social interactions and also low self-esteem and satisfaction. Screening for psychiatric co-morbidities and vulnerability factors is essential for the management of this type of pathology.None Declared


Video game addiction is defined as the steady and repetitive use of the Internet to play games frequently with different gamers, potentially leading to negative consequences in many aspects of life. As recent technological development has given easy access to gaming on many devices, video game addiction has become a serious public health issue with increased prevalence. Many studies have shown that video game addiction leads to changes in the brain that are similar to those that occur in substance addiction and gambling. Evidence has also shown that there is an association between video game addiction and depression, as well as other psychological and social problems. In light of these issues, our review article aims to increase awareness of video game addiction in society. The main objectives of this review are as follows: to describe the mechanism of addiction, to consider whether video game addiction is a real addiction, and to highlight the signs and symptoms of addiction. In addition, we identify the consequences of video game addiction and possible treatments for addicts. The information was extracted from high-quality research papers and reliable websites like PubMed and ScienceDirect. Video game addiction falls into the category of Internet gaming disorders (IGDs), which have been strongly correlated with motivational control issues and are regularly compared with gambling . Many stEvidence has shown that addiction can cause changes in some areas of the brain, such as the prefrontal cortex (PFC), the ventral striatum (VS), and the dorsal striatum (DS) . In 1999Cross-sectional studies revealed that those with IGD played video games longer, usually missed classes in school, had lower grades, reported more sleep problems, and showed more addiction to video games than those without IGD . Yee sugVideo game addiction may have both short and long-term impacts on gamers, including various emotional, psychological, and neurological effects. A few studies have demonstrated that anxiety and depression are common among individuals who are dependent on video games ,12. In tMechanism of addictionResearchers have demonstrated that at the initial phases of the intentional use of any substance, the choice to utilize it is made by the brain, specifically the PFC and the VS, as habituation to utilize and compulsion begins. In the DS, brain activity changes and become progressively activated through dopaminergic innervation . There aWhether it is real addiction or notNumerous governments see the compulsive playing of online video games as a serious general medical problem and have set up treatment facilities, particularly in China and South Korea . HoweverSign and symptomsIt is important to be able to identify the signs and symptoms of video game addiction, and the sooner one looks for help, the better the outcome. As video games are still a relatively new technology, therapists may disregard the signs of video game addiction. To be able to make informed choices and act successfully in navigating addiction, the following signs can be used as a guide .Preoccupation with GamingVideo game addiction starts when gamers become preoccupied with video games, where they will think and fantasize about the game when they are not playing it when they should be focusing on other things, such as schoolwork .Lying or Hiding Gaming UseGamers may play games for uncountable numbers of hours and days, leading to a lack of eating, resting, or personal hygiene. They may also lie to loved ones about what they are truly doing for hours in their rooms. Gamers may tell their parents that they are getting their work done, say that they are using their PC for work, or make up many reasons why they cannot go out and socialize .Loss of Interest in Other ActivitiesAs video game addiction increases, the person’s interest in daily activities they used to enjoy decreases . For exaSocial WithdrawalOne’s character might also change as the addiction increases. For example, social people may remove themselves from their loved ones to invest more time in play. Otherwise normal and happy children may be inclined to simply make friendships in the game, which can become more important than those in real life .Psychological WithdrawalGaming addicts may experience loss when they cannot play a game, as they miss it and feel the need to play it. This inclination can become intense to the point that they become emotionally unstable when compelled to abandon the game. As a result, they cannot focus on anything else except playing .Defensiveness and AngerWhen gaming addicts need to play or when they are compelled to stop playing, they can become defensive and furious. Guardians attempting to set time limits for the game have reported that their children can become angry, unreasonable, and even brutal in response .Gaming Addicts Use the Game World as a Psychological EscapeVideo games, as an easy way to mitigate upsetting emotions, can turn into a safe space that is removed from real-world issues . Those wContinued Use Despite Its ConsequencesFrequently, gamers have the urge to be the best in the game. Therefore, the more they develop and progress in the game, the more they have to play it. This progress is found particularly in journey-type games, where gamers join each other and complete missions in the game together . UltimatConsequencesVideo game addiction can lead to a number of serious consequences. Gamers can forget that they need to sleep and eat, or even how to communicate with people in the real world. Gamers may play for 10, 15, or even 20 hours in a single gaming session. Only a couple more minutes can turn into hours as the gamer progresses to the next challenge. They may also endure various medical issues resulting from back strain, eye strain, and carpel tunnel syndrome. For example, one addicted gamer said that he stopped washing himself, ate very little food, and experienced weight loss . In anotTreatmentResearch on video game addiction treatment is ongoing, only a few clinical trials have been conducted. Some therapists have suggested cognitive behavior therapy (CBT) . As a prCBTBased on the peer-reviewed literature, CBT seems to be the most common treatment for video game addiction and IGD ,38. SpecPIPATICPrograma Individualizado Psicoterapéutico para la Adicción a las Tecnologías de la Información y la Comunicación (PIPATIC) has been used to treat addiction to technology. PIPATIC is an individualized psychotherapy program that is available for people aged 12 to 18 years who have IGD and is designed to integrate several areas of intervention. PIPATIC comprises six modules: psychoeducational, treatment as usual, intra-personal, interpersonal, family intervention, and development of a new lifestyle . The proPharmacotherapyThe medications trial that has been done were on drugs usually used to treat depression or attention deficit hyperactivity disorder (ADHD). Bupropion is one of the medications used for depression. It has been investigated as a treatment for IGD in randomized clinical trials ,44. The Many studies suggest that the changes that occur in video game addicts are similar to those that occur in other addictions, such as substance-related addiction and gambling. The WHO has added video game addiction to the ICD-11, with adolescents being the most susceptible. Video game addiction can lead to many serious consequences for gamers and the people close to them. Although research on video game addiction treatment is ongoing, only a few clinical trials have been conducted on the efficacy of the treatment options, for example, CBT, PIPATIC, and pharmacotherapy.


Standard outcome sets enable the value-based evaluation of health care delivery. Whereas the attainment of expert opinion has been structured using methods such as the modified-Delphi process, standardized guidelines for extraction of candidate outcomes from literature are lacking. As such, we aimed to describe an approach to obtain a comprehensive list of candidate outcomes for potential inclusion in standard outcome sets.This study describes an iterative saturation approach, using randomly selected batches from a systematic literature search to develop a long list of candidate outcomes to evaluate healthcare. This approach can be preceded with an optional benchmark review of relevant registries and Clinical Practice Guidelines and data visualization techniques (e.g. as a WordCloud) to potentially decrease the number of iterations. The development of the International Consortium of Health Outcome Measures Heart valve disease set is used to illustrate the approach. Batch cutoff choices of the iterative saturation approach were validated using data of 1000 simulated cases.Simulation showed that on average 98% (range 92–100%) saturation is reached using a 100-article batch initially, with 25 articles in the subsequent batches. On average 4.7 repeating rounds (range 1–9) of 25 new articles were necessary to achieve saturation if no outcomes are first identified from a benchmark review or a data visualization.In this paper a standardized approach is proposed to identify relevant candidate outcomes for a standard outcome set. This approach creates a balance between comprehensiveness and feasibility in conducting literature reviews for the identification of candidate outcomes.The online version contains supplementary material available at 10.1186/s12874-023-02052-x. Value-based healthcare has emerged in recent years as the primary focus for authorities, decision-makers and the public –3. MedicIn this paper we describe and validate a standardized efficient approach to identify candidate outcomes for the purpose of developing standardized sets and we investigate if this method is able to achieve full saturation using simulated cases, in which the total of candidate outcomes is known. Additionally, we illustrate the utilization of the standardized approach by providing a real-world example.outcomes in the provided examples.The methodology is based on a iterative saturation approach, which can be preceded by benchmark review and/or data visualization techniques to screen (using frequent words in abstracts) the studies that have been extracted from a systematic search using a scoping search. We illustrate practical use of the methodology in the ICHOM standard set for heart valve disease (HVD). Data saturation techniques to identify candidate outcomes have been proposed and used before, nevertheless in literature several algorithms have been used to achieve saturation, and it is unknown if these algorithms reach full saturation or if several candidate outcomes are missed altogether , 11. ThiA systematic literature review is an essential component in identifying candidate outcomes for a standardized outcome set, also called core outcome set in COMET and OMERACT initiatives. It is recommended to conduct a systematic search in collaboration with a medical information specialist . MultiplTo balance the tradeoff between unnecessarily reviewing all these studies and saturation of candidate outcomes  an iterative algorithm was used of randomly selecting a batch of articles from an extensive literature search and keep reselecting new batches of articles until saturation of outcomes is achieved. The steps of this algorithm are described in Table In most domains of disease, a wealth of registries and guidelines exist for the capture of clinical outcomes. These resources provide excellent starting points for the identification of candidate outcomes for a standardized set. In the case of the HVD set these resources included several well-known valve registries, as well as international Clinical Practice Guidelines for the management of patients with HVD identified by the stakeholders. Although, the benchmark review is not based on a systematic search and does not capture all outcomes, it provides an overview of several outcomes and way of measuring them. This method is optional and can be performed preceding the iterative saturation approach to reduce the number iterations needed to achieve maximum saturation.In order to obtain a quick overview of the outcomes that may be discussed in literature data visualization tools can be utilized. A scoping search (using only the disease as search term) at an initial stage can optionally be performed and data visualization tools can provide an overview of frequently used words. For instance, in the HVD set, the search term “Heart Valve Disease” was used in Embase yielding 142,279 articles  is a stochastic process, depending on several parameters. As such, it is difficult to determine the optimal cutoffs of the starting batch and subsequent batches. In order to investigate different cutoffs a simulation study was performed to determine at which values theoretical full saturation will be met. It was hypothesized saturation is depended on several parameters, including:the number of total candidate outcomes,the number of individual outcomes per study,the number of selected papers in the starting batch,the number of selected papers in the subsequent batches,the saturation achieved in benchmark review and data visualization, and.the probability of an outcome being reported in a random paper. This is based on the fact that that some outcomes  are studied more often compared to other outcomes (e.g. left ventricle size), which reflects the real world better than assuming that the probability of an outcome being studied is equal for all potential candidate outcomes.We developed a simulation algorithm in R to simulate 1000 cases for any given combination using the aforementioned parameters. The simulation algorithm details are presented in supplementary Text 1, and can be used by researchers to replicate the simulation in different settings. In the HVD standard set we used 100 papers in the initial batch with 25 papers in the subsequent ones.The iterative approach of our simulation model results in a 98% (range 92–100%) saturation of the candidate outcome for a hypothetical total of 100 possible candidate outcomes based on 1000 simulations with 3 individual outcomes per paper, with 0% outcomes identified by the benchmark review or data visualization. It is worth noting that if benchmark review and data visualization are performed, it this highly unlikely they yield 0% identification of candidates outcomes in real-world scenarios. In this particular case, the probability of encountering a specific outcome in a random study ranged from 40% for outcome number 1 to 5% for outcome number 100 . On average 4.7 repeating rounds (range 1–9) of 25 new articles were necessary to achieve saturation. The relationships between the choice of the initial and subsequent batches and the total number of outcomes are shown in Fig. This number of repeating rounds drops to an average of 3.9 range 1-10, 3.7 range 1-9 and 2.5 range 1-9 if an outcome saturation of 30%, 50%, and 70% is achieved during data visualization and benchmark review, respectively Fig. .The probability of encountering a specific outcome in a random study seems a determining factor for achieving saturation, as simulation showed that if an outcome was reported in less than 5% of the studies in the literature, the probability of being selected in the final candidate outcome set dropped below 75% using a starting batch of 100 studies and repeating batches of 25 studies, assuming 0% saturation from the benchmark, with 3 individual outcomes per study and a total of 100 outcomes. The probabilities of ending up in the final set are marginally improved by choosing larger starting or repeating batches, but this improvement seemed more dependent on the number of individual outcomes per study than the actual number of studies in the starting and subsequent batches  saturation reached using a 100-article initial batch, with 25 articles in the subsequent batches. The R code for this simulation is attached in the supplement and can be used by applied researchers. This approach can be used to obtain a list of candidate outcomes obtained from literature which can be supplemented using qualitative measures  and used in voting processes such as the modified Delphi method to develop a standard outcome set, or a core outcome set.The PRISMA guidelines are commonly used to conduct systematic reviews of the literature, and several studies developing standardized/core outcome sets have done so , 14. TheA saturation approach to extract candidates outcomes in literature has be suggested before, however the proposed algorithms are generally different. The COMET handbook suggest a saturation approach by looking at trials in the past 5 year and perform an additional search to investigate if new outcomes arise , whereasPrior research has been performed to filter searches to limit the search to relevant articles . In thisData visualization and benchmark review could optionally be performed to reduce the number of iterations needed in the saturation approach. Simulation studies showed that it indeed reduced the number of iterations needed to achieve maximum saturation. In this study we did not use natural language processing (NLP) models. The use of such models has been limited due to inconsistent outcome description in trials and published corpora to support outcome detection , 19, howIn this paper we validated a standardized iterative-saturation approach for the selection of candidate outcomes from the literature. These outcomes provide an input for a standardized outcome sets to collect real-world outcome data to improve the understanding of the patterns disease across countries. The proposed approach is comprehensive, efficient and balances the tradeoff between extensively reviewing all literature versus potentially missing out on important outcomes. Simulation studies showed acceptable saturation of candidate outcomes using the iterative algorithm.Below is the link to the electronic supplementary material.Supplementary Material 1


United Nations Universal Declaration of Human Rights states that, “everyone has the right to seek and to enjoy in other countries asylum from persecution”. Latin Americans from several countries  seek asylum in the USA, looking for protection, security, and a way to provide for their families. Those who seek asylum must provide evidence that they meet the definition of a refugee. Despite the declaration of Human Rights, the civil rights of immigrants in the USA have continued to be violated. The denouncement of an e-mail stating that migrant children were being pushed into the Rio Grande river by Texas troopers, a girl dying after being denied medical care, and the installation of a floating barrier by the state of Texas to stop people from swimming to cross the border at the Rio Grande river confirm that the violence against immigrants is far from over, once again crossing the line of basic human rights. Despite the termination of Title 42, the immigration policy implemented during President Trump’s administration that allowed the removal of migrants crossing the USA–Mexico border, President Biden’s restrictions on asylum seekers are still very strict and invite the question of whether his statement on humane treatment and civil rights for immigrants will actually be enforced.The Ulrich and Crosby, Title 42 was a justification to oppress marginalised populations, such as immigrants, those living in poverty, women, and people of colour, and denying access to human rights of immigrants and asylum seekers. More than 13,480 reports of violent conduct, including murder, torture, and kidnapping, have been reported since President Biden took office on Jan 20, 2021. Although COVID-19 cases dropped in most countries months before, Title 42 was only terminated on May 11, 2023, days after the declaration by WHO about the end of the global health emergency. With the termination of Title 42, President Biden proposed a rule to deny asylum to migrants at the USA–Mexico border, which was blocked by judge Jon Tigar from California.At the beginning of the COVID-19 pandemic, Title 42 was implemented as a public health measure that allowed US authorities to expel migrants, including asylum seekers, at the US border. Title 42 was a controversial act ordered by the US Centers for Disease Control and Prevention, without scientific evidence supposed to protect people from being infected by COVID-19. As pointed out by border patrol arrests have increased greatly and, as discussed by Cameron and colleagues, families must stay in shelters that pose risks for their health due to overcrowding, poor sanitation, and precarious infrastructure. Violence against women has also been reported, with high rates of rape and feminicide by people involved in organised crime and by USA and Mexican officers. Children suffer with lack of education and family separation, which have huge impacts on their mental health and increasing risk for post-traumatic disorder. For the children that eventually cross the border, the Deferred Action for Childhood Arrivals programme (DACA), that provided work authorisation and deportation protection for those who entered in the USA as children is no longer an option. In October, 2022, the DACA programme was put on hold on the basis that it was unlawful, preventing new applications and creating speculation about its termination. The programme, implemented by President Obama in 2012, created new opportunities for more than 800,000 children since its start. Although not providing citizenship, one of its benefits was access to employer-sponsored and state-funded health insurance in certain states. One of President Trump’s main goals was to terminate DACA and, although this attempt was blocked by the Supreme Court, the decision to stop new applications has shown how the programme’s fragility. However, President Biden is trying to increase Medicaid and ACA health coverage to those under DACA. In a thoughtful and provocative viewpoint, Park and colleagues presented some possible paths for continuity of care of migrant population in the USA, such as state-level policymaking to expand coverage to all residents despite their migration status, and expanding health insurance eligibility for undocumented migrants.The new restrictions present challenges for people seeking asylum, as those who enter the USA between legal border crossings are considered ineligible. Thus, people who do not request protection in transit countries, such as Mexico, or cross between ports of entry, are disqualified from claiming asylum and denied re-entrance to the USA for 5 years. Asylum seekers must wait in Mexico and are required to wait for their immigration court hearings that can last more than a year. Over the past 15 years, the number of economy and industry as, among other things, workers and tax payers. Undocumented immigrants do not increase violent crime rates, present lower incarceration rates than those born in the USA, and are less likely to be arrested for homicide. It is up to President Biden to decide if the USA will take a step in the right direction to guarantee proper rights for all those that seek asylum. Title 42 showed the consequences of major actions within the migrant population, having a huge impact on the mental health and long-term development of both adults and children. It is time now to reconcile and provide proper support and resources for migrants to the USA.As thousands of people arrive at the USA border requesting asylum, it is only fair that they are treated with the same dignity as any other person. They are vulnerable members of society that have suffered persecution and trauma and their rights must be guaranteed. With the termination of Title 42, the USA is in a position that could be decisive for anyone seeking to immigrate to the country. Immigrants are crucial components of American society and contribute to the


This is the authors’ response to peer-review reports for “Technologies to Support Assessment of Movement During Video Consultations: Exploratory Study.”Response to reviewers, June 7, 2021Limitations to that effect.1. We acknowledge that this exploratory study  has beenIntroduction, Methods, and Multimedia Appendix 1 to address this point.2. Thank you. We are of course aware of the various aspects of movement, and these were taken into account in our literature search and methods. This perhaps was not clear to the reviewer, so we have added sentences to the Limitations section to address this point. Thank you.3. Acknowledged, and we have added a sentence to the 4. We have not been able to find this misspelling  anywhere. CINAHL seems to be correctly spelled both in the main text and in Multimedia Appendix 1.5. Actually, we realize there is a mistake in the text of the main paper in that our literature review was 2017-2021 inclusive. We have added a justification for the choice of date to Multimedia Appendix 1. The reasons for starting with 2017 are as follows:video consultations gives 2465 results, half of which are from 2017 onward. However, if the search is changed to video consultation AND physiotherapy, Web of Science only returns 21 results, all but one of which are from 2017 onward.(1) The routine use of video calls in clinical consultations is relatively recent. Starting with a very simple search of Web of Science on (2) Kubi was introduced to the market in 2012. It was likely that any study making use of it in clinical video consultations was not going to reach press until 2015 at the earliest.(3) As we were also searching via Google and had had a “watching brief” on technology developments related to telepresence robots over the last decade, we thought a 5-year review of the literature was adequate.6. Multimedia Appendix 2 gives considerable detail on each of the products.1. We have added “use of” to the objectives in the Abstract to clarify our focus.Introduction (pages 2 and 3), where we describe how we were aware of the Kubi and Pivo, how we carried out a literature search (as well as various Google searches), and that as far as we were aware, these were the only “off-the-shelf” technologies available at the time.2. Our justification for focusing on these four devices  is provided in the 3. The “hypothetical patients” were “hypothetical” . All testing was between the coauthors.Methods section to clarify “hypothetical patients.”5. As explained above, we have added a sentence to the Thank you (:>).


The nature of the deposits in immune-mediated glomerulonephritis with a membranous pattern and masked IgG-Kappa deposits (MGMID) remains still to be elucidated.We present a case of 33-year-old woman developing a continuous asymptomatic proteinuria (0.8–1 g/24 h) with no overt connective tissue diseases. She tested positive at high titers for SSA antibodies  and at the kidney biopsy histological findings were compatible with an immune-mediated glomerulonephritis with a membranous pattern and masked IgG-Kappa deposits. Also, we demonstrated a positive immunohistochemistry staining for anti-Ro52-SSA antibodies, with a granular positivity in mesangium and along rare glomerular capillaries. To date, only one case of a patient with overt diagnosis of Sjögren’s syndrome with MGMID has been described but a pathogenic role for SSA and SSB antibodies has never been proven.In this case, we described for the first time by immunohistochemistry a Ro52+ granular positivity in the mesangium and glomerular capillaries, potentially paving the way for a better understanding of MGMID. In 2014 Larsen et al.  The MGMID is a recently discovered histopathologic pattern of glomerulonephritis characterized by subepithelial and mesangial deposits of IgG kappa detectable in paraffin immunofluorescence.Some considerations are worth noting from our experience with this patient.Firstly, as initially speculated, MGMID seems to be generally present in young females with autoimmune positive tests. Since their first description , it seemSecondly, our patient presented with high titers of SSA, as often seen in Sjögren’s syndrome and SLE. To date, only one case of a patient with overt diagnosis of Sjögren’s syndrome with MGMID has been described. However, a pathogenic role for SSA in inducing renal manifestation has never been speculated . InteresFinally, our patient did not experience a worsening of the clinical setting after more than 24 months of follow-up. Outcomes of MGMID are heterogeneous ranging from spontaneous remission to progression to end stage renal disease, making a better characterization of the patients’ profile highly needed to guide therapeutic choices.With MGMID now increasingly identified as a novel clinical entity, international efforts are needed to better understand prognostic factors associated with different renal outcomes.


BackgroundThis study aimed to explore patients’ subjective utility for a patient information video (PIV) on cataract surgery and analyse the use of a quick response (QR) code as a mode of delivery of the PIV.MethodsA total of 500 patients were included in the study. All patients were given a paper form of the patient information leaflet (PIL) as the standard of care (SoC) in addition to a digital QR code to access a supplementary PIV. The questionnaire explored the patients’ understanding of cataracts, the risks and benefits of cataract surgery, and their experience accessing and using the QR code.ResultsA total of 321 responses were collected (64% response rate). The majority were female (55%), with a mean age of 75 years. Among these, 69% (n = 222/321) managed to watch the video. A statistically significant association was reported between prior experience with QR codes and the ability to watch the video (p<0.001). The most common reason for not watching the video was no device . Ninety-one percent of the patients who watched the video expressed a desire for additional healthcare videos in the future.Overall, most patients  acknowledged that the PIV was easier to understand when compared to paper-format information, with a minority of patients reporting the PIV missing information that was covered on paper (n=2/222).ConclusionsThe provision of PIV supplementation as a part of the cataract surgery referral pathway is an innovative method of providing patient information in a more interactive way, with positive feedback from patients. Digital health is having a profound effect on our healthcare systems, enabling new models of care, improving quality, efficiency, and patient experience, as well as supporting more integrated care and improving the health of the population. Cataract surgery is the most frequently performed surgery in the UK, with approximately 500,000 surgeries performed annually in England and Wales . AlthougThis single-centre, prospective study was conducted at the ophthalmology department of Ninewells Hospital, Dundee, Scotland. A total of 500 patients with a diagnosis of cataracts made by a community optometrist were enrolled. These referrals included those with other sight involving ophthalmic pathologies , but the referral required the examining optometrist to commit to the conclusion that cataract was the principal reversible factor impacting vision.All patients were provided with a cataract letter pack, which informed the patients that they could now benefit from cataract surgery while highlighting that the surgery is voluntary, and the information enclosed aimed to help them make the correct decision regarding risk and benefit. The pack contained: 1) a cataract surgery consent form; 2) a cataract surgery information leaflet in paper form as the current standard of care (SoC); 3) a printed QR code linked to a supplementary patient information video on cataract surgery  and a QR code. The video was uploaded to YouTube as a public online video. The video is exclusively accessible in the English language, supplemented with closed captioning that encompasses crucial information. This video begins by discussing the diagnosis of cataract and its symptoms. It then explains cataract surgery in broad conceptual terms, followed by some pointers to risk and benefit, and refers to the standard printed sheets where more detail can be found. The end of the video describes what to expect after the operation, including the visual outcome, post-operative care, and follow-up. This video was made to cover key information for cataract surgery, similar to that in the patient information leaflet.The cataract surgery patient information video was produced with the involvement of the wider cataract team at Dundee Ophthalmology Department, Scotland, providing patients with unrestricted access to a four-minute, 30-second video showing the consent dialogue and all relevant aspects of the patient journey. No technical details of surgery or images that might be deemed upsetting were included. The video afforded the opportunity to interview other members of the team (theatre and ward nurses) as well as show the physical environment of the ward and theatre to render these more familiar when encountered. The video was titled “Your Cataract Surgery: A Patient Information Video” (Account: EYE Surgeon) and was made available as a character string , which used a five-point Likert scale to grade their knowledge of cataract surgery, satisfaction with the quality of the video, and preference for the format of information delivery. The following questions were rated as follows: strongly disagree, disagree, neither agree nor disagree, agree, strongly agree• I found the video clear and easy to understand.• I feel the information was too detailed.• I feel I understood my treatment options.• I feel I understand the risks, and I want to.• I feel I was free to choose not to go ahead with surgery if I didn’t want to.• I found the video easier to understand than the paper information.• I found the video missed out on some important information the paper covered.Other question types involved multiple-choice and full-text answers.A total of 321 respondents completed the questionnaire (64% response rate). The age range of the respondents was 45-97 years (mean age: 75 years). Overall, 53% of respondents were aged over 75 years (approximately the mean age for cataract surgery in Scotland). The female-to-male ratio was 1.2:1. Overall, 69% of the cohort managed to watch the video (n=222/321). Of 321 participants, 42% (n=134/321) had previously used QR codes, presumably becoming more ubiquitous in restaurants and advertisements in the COVID era. Smartphones were the most widely used device , and only 28% (63/222) of the participants used a tablet to watch the video. The owners of the device used were mainly the patients themselves , followed by family members , and less commonly, a device belonged to a friend . In terms of video viewing, most patients reported watching the video between one and two times , with a few repeating it three times or more . The most common reasons for not watching the video were no devices  and no internet access . Other recorded reasons included ‘not sure how to do this’ (26%) and ‘not interested’ (7%).A five-point Likert scale was used to grade patients' understanding of the cataract surgery video Figure .The majority, 89% (n=199/222), of patients agreed or strongly agreed that the video was clear and easy to understand. In terms of the usefulness of the video in guiding decision-making for surgery, 84% (n=187/222) reported they understood the treatment options, while 83% (n=185/222) agreed or strongly agreed they understood the risks and benefits of cataract surgery as well as they wanted to. Significantly, 87% (n=194/222) agreed that they felt free to choose not to have surgery if they did not want to, implying the video or the large information pack did not result in pressure to ‘conform’. Generally, most patients  acknowledged that the PIV was easier to understand when compared with standard paper format documentation, with only two patients (n=2/222) reporting the video as missing information better or more fully covered by the printed information. Ninety-one percent of patients who managed to watch the video stated they would like to have more healthcare videos in the future.The positive impact of previous QR code usage and the ability to watch the patient information video was found to be statistically significant in our study (p<0.001). With respect to age, increasing age was found to be negatively correlated with prior usage of QR codes (p=0.04) and predictive of an inability to watch the video (p=0.01). However, patients’ preference to have more healthcare information videos in the future was not significantly related to age or gender.Ideally, the patient and doctor should have a personalised discussion regarding the procedure, benefits, risks, alternatives, and expected outcomes of all planned surgeries. Communication should be honest, the level of detail appropriate, and all exchanges should be open and free. It should be comprehensible and tailored. It should afford the opportunity for questions, and when all outcomes are considered, the option of doing nothing (no surgery) must always be explicit. Cataract surgery is clearly an exemplar for such ethically fair shared decision-making, as there is no biological urgency and the intervention is not time-bound or prejudiced by delay, within reasonable bounds. Several studies have shown that clear and effective patient education before surgery is imperative for increasing patient satisfaction and reducing pre-operative anxiety and post-operative complications . This caExisting demands on productivity limit surgery and patient contact time available, which directly impacts the time available for appropriate consenting quality and the time available for the patient. This has been described as the efficiency-thoroughness trade-off (ETTO) . This ofVideo-based media are one of the most ubiquitous forms of communication in the modern age, as they provide a consistent form of educational information and communicate concepts realistically and visually. In ophthalmology, the effects of different presentation methods on patient knowledge have most commonly been investigated within the informed consent process for cataract surgery . HoweverThis Quality Improvement Project (QIP) took the form of a non-inferiority pilot in the sense that the innovation was compared with the current standard of care. It is obvious that with respect to normal consent, as practised in the National Health Service, there is no standardisation of what content is delivered, at what pace, and with what degree of detail and time for dialogue is admitted. One advantage of the PIV is that it can be so recorded as to ensure every person watching receives the same content and emphasis when these are agreed upon as the minimum ‘data set’ for any patient. One interesting and unanticipated finding was that, while only 69% of the cohort reported accessing the video, 71% (respondents) requested that they be placed directly on the waiting list for surgery. It is not obvious that the numbers overlap entirely, but certainly, some patients who opted for surgery had not viewed the PIV. Given that they were empowered and happy to do so, this may reflect that for many respondents, the printed information is sufficient. It must always be appreciated that if a patient declines any given degree of detail in an offered explanation in any consent process, that is one's right. As has been said, “A patient is using their autonomy when they choose to surrender their autonomy” [The limitations of the current study are the inability to correlate surgical outcomes or Patient-Related Outcome Measures (PROMs) with the choice made and the predictive validity of the levels of confidence and satisfaction with the PIV and QR code delivery modality with acuity or quality of life outcomes. This is a limitation of the anonymous nature of the questionnaires used in this QIP. Furthermore, the paper-based delivery of the code to access the PIV means that recipients who do not possess an internet connection or a device cannot proceed. If the information is provided on a web-based programme or device on the optometry premises at the point of referral, access would be afforded by the definition of that modality. Such systems exist, and we propose to audit this next iteration of the PIV.Direct optometrist-listing for cataract surgeries (“Optometrist to Operation”) through a streamlined pathway incorporating video and QR code approach benefits patient satisfaction, autonomy, beneficence, and fairness while streamlining care delivery processes within the cataract team. The fulfilment of cataract surgery provision remains a continuous challenge within NHS Scotland. We show that with minimal investment, collaborative working with primary care services, and a smart redesign process, local provision and access can be possible.