Scholarship is a key activity in health professions education (HPE). When disseminating scholarly work, how one selects the journal to which they submit is often argued to be a key determinant of subsequent success. To draw more evidence-based recommendations in this regard, we surveyed successful scholars working in HPE regarding their perspectives and experiences with journal selection.We conducted an international survey of HPE scholars, investigating their decisions regarding journal choice. Corresponding authors were identified from a sample of 4000 papers published in 2019 and 2020. They were invited via email with up to four reminders. We describe their experience and use principle component and regression analyses to identify factors associated with successful acceptance.In total, 863 responses were received (24.7% response rate), 691 of which were included in our analyses. Two thirds of respondents had their manuscripts accepted at their first-choice journal with revisions required in 98% of cases. We identified six priority factors when choosing journals. In descending order of importance, they were: fit, impact, editorial reputation, speed of dissemination, breadth of dissemination, and guidance from others. Authors who prioritised fit higher and who selected a journal earlier were more likely to have their manuscripts accepted at their first-choice journal.Based on our results we make three recommendations for authors when writing manuscripts: do not be disheartened by a revise decision, consider journal choice early in the research process, and use the fit between your manuscript and the journal as the main factor driving journal choice.The online version of this article (10.1007/s40037-022-00698-9) contains supplementary material, which is available to authorized users. Scholarship in Health Professions Education (HPE) is considered one of the key activities of clinician educators . This coFinding answers to such questions would be particularly timely given increased global awareness of equity, diversity, and inclusion issues. Medical education literature in particular has been dominated by research from North America, the United Kingdom, the Netherlands, and Australia , 5. OtheWhat priorities do authors hold when selecting where to publish their work? To what extent do those priorities vary between different demographic groups? Multiple factors have been previously identified as important considerations for medical education authors, including impact factor and prestige . Work inOf course, authors’ priorities for pursuing a particular journal are not the only determinants of where a work is eventually published. As such, it is important to explore their choices in relation to what happened to the paper with respect to peer review and subsequent revision. While long known to have reliability problems, peer review’s primary value may be highlighting diversity of opinion, helping authors to see ways in which their work might be misinterpreted relative to the way in which it was intended . A studyThese big picture issues require further exploration if we are to both offer good advice to authors in our field and reflect on the strengths and priorities of the field as a scientific enterprise in its own right. With this study, therefore, we surveyed successful scholars working in HPE regarding their perspectives and experiences with journal selection.We conducted a cross-sectional online questionnaire study of recently published HPE scholars. Ethical approval was granted by the Keele Institute for Innovation and Teaching Excellence—Educational Research Ethics Committee (KIITE-EREC) at Keele University (Ref: KR-210048).To identify a sample, we generated a list of HPE papers published in 2019 and 2020 by searching PubMed using the query: ‘Education, medical’ OR ‘health professions education’ across all database fields. We did not deliberately exclude non-English articles, but our search strategy would have implicitly focused on the English literature. Letters and editorials were excluded because authors of such pieces do not generally undertake the same choice-making processes regarding where to submit. We then extracted the names and email addresses of the corresponding authors from all remaining papers. Duplicate names were reviewed and the most recent research paper for each unique author was selected. We then randomly selected 4000 unique corresponding authors and invited them, via email, to complete our questionnaire. Four reminders were sent at one-week intervals. For the same reason as expressed above, exclusion criteria applied after survey completion were (a) the author identified the manuscript as a letter or editorial and (b) the author identified the manuscript as having been commissioned.We developed a novel questionnaire for this study by conducting a literature review aimed at identifying any existing measures that could be adapted to suit our research questions and supplementing that with personal experience to identify important aspects of journal choice. Individual items were generated following guidelines for best practice. This included stating both positive and negative sides in question stems, developing response options that were comprehensive and mutually exclusive, and using balanced scales with construct-specific labels . QuestioWe then submitted the draft for expert review by inviting a panel of four senior HPE researchers  to offer feedback on the questionnaire regarding its clarity and relevance. We used their guidance to revise the survey, rephrasing unclear items and adding response options, and conducted a trial administration with five early career authors to identify any further concerns regarding clarity and to provide an accurate estimate of duration for completion.The final version of the survey included 59 items divided into 10 sections . Participants were presented with the title of the manuscript that was used to identify them and they were asked to answer all questions based on that manuscript.p-values less than 0.01 to be statistically significant. We present categorical variables as frequencies with percentages and continuous variables as means with their standard deviation.We used SPSS version 27  for all analyses and considered To assess for nonresponse bias we conducted a wave analysis . That isWe grouped career stages into trainee , junior academic (below senior lecturer/associate professor), and senior academic (senior lecturer/associate professor and above). We grouped country of corresponding author into those that are most represented in the HPE literature  , 5 and oTo reduce data and create more robust measures of the constructs of interest, we performed principal component analyses (PCA) on the 10 “motivation for publication” items and the 21 “journal priority items” with oblique rotation. The Kaiser-Meyer-Olkin measure verified sampling adequacy for the two analyses at KMO = 0.775 and 0.839 for motivations and priorities, respectively. Subsequent analyses used computed factor scores based on the mean of their components. Missing data were replaced with item means where possible.Finally, we performed linear and logistic regression analyses to identify associations between author demographics and priorities with submission outcome. We included the stage at which authors decided on a first-choice journal in these models because deciding early and tailoring one’s article to the journal style is commonly advised.Of the 4000 email invitations, 509 were returned as undeliverable. Of the remaining 3491 individuals, 863 responded to our survey, giving an overall response rate of 24.7%. From this group, we excluded 98 responses focused on ineligible contributions to the literature , 3 duplicate responses, and 75 incomplete responses (33 completed the consent form but not the questionnaire and 42 completed the demographic items only). Our final dataset, therefore, consisted of 691 responses, a final response rate of 21.7%  . Wave anRespondents were aged 22 to 90 with a mean of 44.8 (SD = 11.2) years. They had a median of 27  publications. Of the respondents, 471 (68%) were from the dominant HPE publishing countries . Further demographics are presented in Table S1, found in ESM.p = 0.16). The same is true for those whose corresponding authors varied in experience level—trainees, junior academics, and senior academics = 57.1%, 68.8%, and 68.2%, respectively ; for those whose research type prioritization differed—quantitative, qualitative, and mixed methods = 66.1%, 71.4%, and 64.9%, respectively ; and for male vs female corresponding authors = 61.7% and 70.1%, respectively .Manuscripts were initially submitted to 233 different first-choice journals. Of the 337 (63.5%) manuscripts that were accepted at the first journal to which they were submitted, 6 (1.8%) were accepted without revisions, 172 (51.0%) were accepted after minor revisions, and 159 (47.2%) were accepted after major revisions. These manuscripts required a mean of 1.4 (SD = 0.7) rounds of revision. The likelihood of being accepted at the first journal to which authors submitted was comparable for those submitting from a “dominant” country (67.9%) relative to a “non-dominant” country . For those rejected after peer review, 8 (9.1%) tweaked the wording, 24 (27.3%) made changes to reporting without significant changes to content, 22 (25%) made substantial changes to the manuscript, and 5 (5.7%) just resubmitted the original manuscript. When comparing the 38 that made substantial changes to the 179 who changed formatting, wording, or reporting, the average number of journals pursued before publication was achieved was 2.6 and 2.5, respectively . The average length of time the subsequent journal required to offer a first decision was 6.7 weeks. There was no significant difference in the duration between rejection from first journal and final acceptance between those who made substantial changes  and those who made formatting, wording, or reporting changes  .Journals took a mean of 8.4 (SD = 7.8) weeks to make a first decision and overall, the process took a mean of 19.6 (SD = 19.6) weeks between first submission and ultimate acceptance. On average, papers were sent to a total of 1.5 journals before publication was achieved. Of the 194 (36.5%) manuscripts that were not accepted at the first journal, 105 (54.1%) were rejected without peer review and 89 (45.9%) were rejected after review. The modal approach to revising manuscripts before submitting to another journal was to change the formatting to meet the new journal’s requirements; this was the case for those that were rejected after peer review and without peer review but the proportion who fell into that category varied markedly , respondents’ motivations for publication were as follows: to communicate with others , to advance knowledge in the field , to develop national/international reputation , to support career development of co-authors , to get feedback from peer reviewers , to enable networking with others in the field , to enable promotion or other type of career advancement , to enjoy the thrill of seeing work in print , to assist with winning grants and research support , and to act as a catalyst for attracting high quality staff and students  (Table S2 in ESM).The application of principal component analysis to these motivations identified three factors with eigenvalues greater than 1; they explained 58.9% of the variance (Table S3 in ESM) and the scree plot’s inflexion point further suggested that three factors underlaid the responses to individual questions. Content review of the item clustering suggested that the three factors represent motivation for personal promotion, desire to advance the field’s knowledge, and capacity building.Multivariate linear regression analyses Tab.  performeRespondents’ ratings indicated that the most important priorities when selecting a journal in the first instance were match between the journal’s readership and the audience the author hoped to reach (mean = 4.13) along with focus of the journal (4.12). These were followed by familiarity with journal (3.66), manuscript types accepted (3.63), reputation for publishing rigorous research (3.63), database indexing (3.48), and impact factor (3.47) (Table S4 in ESM). In response to a free text question eliciting any other priorities, three other factors were frequently reported: responding to a call for a special issue, having published previous work from the same research programme in the journal, and a requirement to submit to that journal as a condition for abstract acceptance at a conference.PCA identified six factors with eigenvalues greater than 1 that explained 61.9% of variance and were reinforced by the location of the inflexion point on the scree plot (Table S5 in ESM). Content analysis of the items within each cluster suggested that these factors reflect editorial reputation , fit between manuscript and journal , guidance from others , speed of dissemination , impact , and breadth of journal dissemination .Multivariate regression analyses Tab.  indicateAn additional multivariate logistic regression demonstrated that the extent to which an author prioritised fit yielded the greatest odds of being accepted at the first journal (Exp(B) = 2.05, 95% CI 1.48–2.83) followed by the extent to which they prioritised speed of dissemination (Exp(B) = 1.78, 95% CI 1.39–2.29). Prioritising journal impact reduced the odds of being accepted at the first journal (Exp(B) = 0.38, 95% CI 0.29–0.50) as did deciding later in the manuscript writing process to which journal to submit (Exp(B) = 0.78, 95% CI 0.67–0.91) (Tab. Over three quarters of participants felt that peer reviewers’ comments enabled them to improve their manuscript either a little (50.9%) or a lot (27.8%). A similar 74.4% of participants felt their final paper was better than the original submitted.p < 0.001). More interesting, however, is that the factors most associated with whether the author perceived that the feedback enabled them to improve their manuscript were the perceived knowledge of the reviewers  and the perceived constructiveness of the reviews . No correlation was seen between perception of review and duration from first rejection to ultimate acceptance for manuscripts that were not accepted at the first journal . Those who had made substantial changes to their manuscripts before submitting to a second journal had a more positive view of the peer review feedback they had received (mean score = 3.2) compared to those that made cosmetic changes .Authors who ultimately had their manuscripts accepted at their first-choice journal had more positive views of the peer reviewer feedback received (mean score = 3.5) than those who did not . We also found that deciding on the journal to which one intends to submit one’s manuscript earlier within the research process was associated with higher odds of acceptance.Contrary to prior research, the majority of our respondents felt that peer review enabled them to improve their manuscripts . UnsurprThis is the first survey of HPE scholars’ motivations and priorities when publishing manuscripts although it builds on previous qualitative research . While pSecond, we have through necessity adopted a cross-sectional design. This makes it difficult to make causal inferences and makes our study susceptible to recall and social desirability biases . Indeed,Based on our findings we can offer a number of recommendations to scholars in the field. First, do not be disheartened by a ‘revise’ decision in the way that we have often observed new authors to be; an invitation to revise is an expression of an editor’s interest. Nearly all manuscripts that were published at the ‘first-choice’ journal were accepted only after revisions were made. Not receiving such an offer, however, does not necessarily mean the issues cannot be addressed or that a journal that better ‘fits’ the scope of the project cannot be found. Authors submitted their manuscripts to 1.5 journals on average prior to publication and we suspect that number to be an under-estimate given the direction of bias that is most likely to impact upon these data.Second, start thinking about the journal to which you would ideally submit early in your research process. In doing so, consider where your manuscript best ‘fits’ in terms of the scope of the journal and matching your work to their readership to maximise your chance of acceptance. Prioritising fit was not associated with an increase in duration between submission and acceptance compared to prioritising speed of dissemination, and the overall delay between manuscript completion and publication is likely to be lowest if the right journal is selected first rather than sending one’s article to a different journal for the wrong reasons.In determining where one’s manuscript might best ‘fit,’ we suggest authors familiarise themselves with a breadth of journals through reading their articles, editorials, author instructions, and discussing journal selection with experienced HPE colleagues.SurveyTable S1 Demographic characteristics of included respondentsTable S2 Participants’ ratings for motivations for publication itemsTable S3 Summary of principal component analysis of motivations for publication (n = 691)Table S4 Participants’ ratings for priorities for journal choice itemsTable S5 Summary of principal component analysis of priorities for journal choice (n = 688)


ZmCBM48-1, which contained a carbohydrate-binding module 48 (CBM48) domain. ZmCBM48-1 was highly expressed in the maize endosperm and was localized in the plastids. Compared with the wild type lines, the overexpression of ZmCBM48-1 in rice altered the grain size and 1000-grain weight, increased the starch content, and decreased the soluble sugar content. Additionally, the transgenic rice seeds exhibited an alterant endosperm cell shape and starch structure. Meanwhile, the physicochemical characteristics (gelatinization properties) of starch were influenced in the transgenic lines of the endosperm compared with the wild type seeds. Furthermore, ZmCBM48-1 played a positive regulatory role in the starch synthesis pathway by up-regulating several starch synthesis-related genes. Collectively, the results presented here suggest that ZmCBM48-1 acts as a key regulatory factor in starch synthesis, and could be helpful for devising strategies for modulating starch production for a high yield and good quality in maize endosperm. Starch directly determines the grain yield and quality. The key enzymes participating in the process of starch synthesis have been cloned and characterized. Nevertheless, the regulatory mechanisms of starch synthesis remain unclear. In this study, we identified a novel starch regulatory gene,  Maize is one of the most vital staple crops worldwide, and can provide a major energy resource consumption for humans and livestock. Starch accounts for around 75% of the dry matter in the maize endosperm and directly determines the maize quality and yield . With thStarch is synthesized in the plastids of photosynthetic and endosperm cells . In endoOsZIP58 regulates the starch synthesis in rice by changing the amylose content [ZmDOF36, a member of the DOF gene family, positively regulates the starch synthesis in maize [ZmbZIP22 was proven to alter the starch content and structure of maize and rice [ZmZHOUPI, which belongs to a bHLHTF, plays a crucial role in kernel development [ZmbZIP9 binds the promoter cis-elements of starch synthesis-related genes to regulate starch synthesis in maize [Plenty of research has indicated that transcription factors (TFs) play an important role in starch synthesis. According to a report,  content . ZmDOF36in maize . The oveand rice . ZmZHOUPelopment . ZmbZIP9in maize .FLO6 encodes a CBM48 domain-containing protein that is involved in starch granule formation and synthesis in rice [In addition to the transcription factors (TFs), it has also been reported that carbohydrate-binding modules (CBMs) are involved in starch metabolism. CBMs are a type of non-catalytic structural domain that mediate the binding of proteins to polysaccharides, such as cellulose, chitin, and starch . The car in rice . Similar in rice . HoweverZmCBM48-1 (GRMZM2G122274), from the maize genome was isolated in this study. Our results indicate that ZmCBM48-1 was specifically expressed in the maize endosperm and was localized in the plastids. The overexpression of ZmCBM48-1 in rice can change the grain thickness and 1000-grain weight. Importantly, the starch content, starch structure, and physicochemical characteristics of starch were influenced in the ZmCBM48-1-overexpressing rice endosperm. Compared with the wild type, the expression patterns of the starch synthesis-related genes were also regulated in the transgenic rice endosperm. Collectively, these results suggested that ZmCBM48-1 may perform essential functions in the process of maize starch metabolism, and could help to devise strategies for modulating starch production for a high yield and superior quality in the maize endosperm.Here, a CBM48-containing gene, which was named The carbohydrate binding module 48 (CBM48) family is one of the largest families of CBMs, which has been identified as a specialized starch-binding domain in recent reports ,19. HoweZmCBM48-1 from different maize tissues were detected through publicly available genome-wide transcript profiling. ZmCBM48-1 had a higher expression in the maize endosperm than the other tissues  possessing different mRNA expression levels were used to investigated the function of ZmCBM48-1 in rice seed development  and the maximum absorption wavelength (λmax). The BV and λmax of the amylose and amylopectin were indeed increased in the transgenic lines compared with the WT lines  and λmax. Previous studies have shown that the BV and λmax values can provide a key indicator of the starch content and structure, and represent the ability of starch binding to iodine [ZmCBM48-1 exhibited loosely packed starch granules compared with the WT lines. These results demonstrate that ZmCBM48-1 indeed regulates starch metabolism in the seed endosperm.Starch consists of amylose and amylopectin and has important application value in the economy and industry. Starch synthesis is a complex metabolic process that requires the coordinated activities of a series of enzymes . To invendosperm . Intereso iodine . MoreoveZmCBM48-1 in starch synthesis, the expression profiles of nine starch synthesis-related genes were characterized in the transgenic line endosperm. The results indicated that the expression patterns of these genes were upregulated in the ZmCBM48-1-overexpressing transgenic lines. Obviously, further research, including screening the direct interaction proteins with ZmCBM48-1 and the production of transgenic maize lines, will be needed in future research.Starch synthesis is catalyzed by four types of enzymes: AGPase, SS, SBE, and DBE ,5. PreviZmCBM48-1 in rice. The overexpression of ZmCBM48-1 in rice increased the starch content and changed the starch composition and starch structure compared with the WT lines. In addition, the gelatinization properties of the endosperm starch also influenced the transgenic lines. Moreover, the expression profiles of the starch synthesis genes were also upregulated in the transgenic lines. These results suggest that ZmCBM48-1 is a potential regulatory factor in starch synthesis, but whether it maintains the same function in maize is still unknown. In future research, we will screen the interaction protein and produce the overexpression and knockout methods in the maize line to clarify the regulatory mechanism of ZmCBM48-1. More importantly, ZmCBM48-1 regulated downstream genes will be screened to explore whether they participate in the metabolic regulation network. Future work will discover the molecular mechanism of ZmCBM48-1 and provide further insight into high-yield and high-quality maize breeding.In summary, our study demonstrated the function of The maize (B73) seedlings were grown at 26–28 °C for a day length of about 13.5–14 h and with 65% air humidity in a greenhouse. Wild type (WT) rice (Zhonghua11) and transgenic rice lines were grown under natural conditions.The sequence analysis was performed as described previously . BrieflyTM III reverse transcriptase (Invitrogen) was used for generating the cDNA. The qRT-PCR was carried out using procedures described previously [Actin1 was used as a control for the expression analysis. To analyze the expression of the starch synthesis-related genes, samples of 6 DAP endosperm, 9 DAP endosperm, 12 DAP endosperm, and 18 DAP endosperm of WT and transgenic rice lines (mixed samples of different transgenic lines) were also collected for the qRT-PCR test. The rice OsTublin gene was used as a reference gene  endosperm, 9 DAP endosperm, 12 DAP endosperm, 15 DAP endosperm, 18 DAP endosperm, 21 DAP endosperm, and 24 DAP endosperm were collected for RNA extraction, separately. RNA extraction was performed according to the manufacturer’s protocol of the RNAiso plus kit , then SuperScripteviously . The valnce gene . All of ZmCBM48-1 (GRMZM2G122274) was inserted into the pCAMBIA1301 vector, then the construct was introduced into O. sativa japonica cv. Zhonghua11, as described previously [ZmCBM48-1-overexpressing lines, and two homozygous T3 transgenic lines (L4 and L7) were identified for further analysis.The open reading frame (ORF) of ZmCBM48-1 was amplified with specific primers . The fully filled grain thicknesses were detected using a vernier caliper from 200 randomly chosen seeds.The total starch contents of the rice endosperm were measured using the starch assay kits following the instructions provided . The iodine colorimetric method  was used to detect the amylose content. To determine the amount of amylopectin, the amylopectin assay kit was performed following the manufacturer’s protocol . The soluble sugar was measured following the method by . The totFirst, 18 DAP rice seeds of transgenic and WT lines were collected for the analysis of seed development, following . BrieflyTo detect the starch structure of the rice seeds, SEM  was used based on research from a previous study .t-test.Values are shown as mean ± standard deviation (SD). Statistical analyses were performed using SPSS v16.0 software based on Student’s ZmCBM48-1 positively regulate the starch synthesis by upregulating the expression levels of starch synthesis related genes.In this study, we identified a novel starch regulatory gene, ZmCBM48-1, which contains a carbohydrate-binding module 48 (CBM48) domain. ZmCBM48-1 was highly expressed in maize endosperm and localized to the plastids. Compared with the wild type lines, overexpression of ZmCBM48-1 in rice altered the grain size and 1000-grain weight, increased the starch content and decreased the soluble sugar content.


The problem of drug delivery often concentrates on the prolongation of drug activity. Application of natural polymers which are biodegradable and inexpensive is in the interest of many researchers. The aim of this study was the application of newly synthesized starch derivatives as potential functional excipients proposed for hydrophilic gel with lidocaine hydrochloride (LH) to prolong drug release from the hydrogel matrix. In our study, we investigated the effect of starch modified with citric acid on the release kinetics of LH using UV-VIS and Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), as well as viscosity and pH measurements. We demonstrated the effectiveness of citric-acid-modified starch in prolonging the release of LH from methylcellulose gel. Lidocaine hydrochloride (LH) a is a weApplication of this sort of starch has been an interest of our group since 2020 , and wasThe aim of the work was the application of newly synthesized starch derivatives as potential functional excipients, proposed as components of hydrophilic gel with LH, for prolongation of drug release from this hydrogel.The following materials were used in the study: methylcellulose , lidocaine hydrochloride monohydrate  and native potato starch (NPS) . Modified starch (S1–S4) was prepared by the University of Environmental and Life Sciences .The process of cross-linking of NPS with citric acid was carried out with a slight modification of the roasting temperature, in accordance with the methodology developed by Klaushofer et al. (1978). Appropriate amounts of acid (2.5 and 5.0 g per 100 g dry weight of starch) were dissolved in 100 mL of water. The pH was adjusted to pH = 3.5 with 1 mol/L NaOH.The obtained starch paste was left for 12 h at room temperature and then dried in an oven  at 50 °C for 12 h. The samples prepared in this way were divided into two portions, which were roasted at two temperatures, 120 °C and 140 °C, respectively, for 3 h. Each sample was rinsed three times with 96% ethanol. The resulting precipitate was dried in an oven at 30 °C for 12 h, ground in a laboratory mill and sieved through a mesh of 400 µm . The folHydrogels based on MC were prepared according to The release study was performed using cellulose membrane tubing of 14 kDa MWCO  as donor compartment immersed in the flask with 450 mL of distilled water as an acceptor compartment at a stirring rate maintained at 100 rpm. Two parallel measurements were performed in extraction cells by sampling 3 mL of the acceptor fluid with return of the medium at 25 °C every 5 and 10 min for 2 h. Analysis of the samples was performed using a UV/VIS spectrophotometer  at 272 nm, according to the available bibliography . The staThe results were examined according to the zero-order kinetic, first-order kinetic, second-order kinetic and Higuchi models. The applied kinetic models are based on Fick’s first law, where the amount of substance diffusing in time through a given surface perpendicular to the direction of diffusion is proportional to the surface area, concentration gradient and time . The zerLH was dissolved in distilled water, and appropriate amounts of S1–S4 were added to the solution, which is shown in −1 to 4000 cm−1 at 32 scans per sample and a resolution of 4 cm−1.An infrared spectrophotometer with Fourier transformation (FTIR) and attenuated total reflectance (ATR) appetizer  with OMNIC software was used to identify the possible interactions between LH and starch. The prepared formulations HS1–HS4 were compared with the standards of the pure substances. The spectra of powders were recorded at wavelengths of 400 cmw/w, and dried formulations (HS1–HS4) were grated to a powder and studied using differential scanning calorimetry (DSC). The study was performed in differential scanning calorimeter . Samples of 3–5 mg were scanned at a constant heating rate of 5 K/min in the temperature range from 0 to 350 °C, in aluminum containers under nitrogen flow of 50 mL/min.The samples of dried S1–S4, LH, their physical mixtures of 1:1 µ is dynamic viscosity [mPa·s]; t is passage time of the ball [s]; d1 and d2 are densities of the ball and the samples, respectively [g/cm3]; K is the ball constant [mPa·cm3/g]; and F is a working angle constant.The dynamic viscosity of formulations F1–F4, and REF was studied in the Höppler viscometer . The fall time of the steel ball in the gels at the angle of 70° was measured at 35 ± 0.5 °C and the viscosity was calculated according to the equation:The pH of the formulations F1–F4 and REF was assessed in potentiometrically in CX601 device  connected with electrode EPS-1  at 22.5 ± 0.5 °C.The samples were visualized in a scanning electron microscope EVO LS15  at 20 kV after dehydration with ethyl alcohol and gold plating with Scancoat 6 sputtering machine .The release courses of LH from the vehicles containing methylcellulose doped with the modified starches S1–S4 are presented in The parameters of kinetic equations of zero-order, first-order and second-order kinetics models as well as of the Higuchi model are presented in The spectra of pure LH, as well as the spectra of modified starches and formulations composed according to The results of DSC analysis presented in The viscosities of formulations F1–F4, and the reference formulation REF are gathered on the graph in The pH of applied modified starches is presented in The morphology of applied starch particles is presented in The initial parts of the release process are visibly curved on the graph, whereas the further parts are more straight-lined A–C. Thusw/w) of the starch carrier in our earlier study [t-test with Bonferroni correction α = 0.01, p = 0.0130. Kanwar et al. [The release patterns of evaluated samples of hydrophilic gel with LH gave variated results in the terms of kinetic model. The F0, F1, F4 and REF samples represented, according to the calculations, release model of Higuchi, which is usually applied to hydrophilic gels. In the case of F2, the second-order kinetics was indicated, whereas in the case of F3, the first-order kinetics. The present results are similar to our previous data which reflected, among others, β-escin release form methylcellulose gel with acetylated starches . In the er study . This thr et al.  showed tr et al. . Howeverr et al. . Accordir et al. . The pro−1, the C-H stretch bonds participating in the ring at 3180 cm−1 and a set of peaks from 3034 to 2920 cm−1 for the C-H bonds receiving in combination. Vibration at 1655 cm−1 indicates the presence of the C=O stretch bond, and peaks at 1540 and 1471 cm−1 are related to the C-C stretching bonds in the aromatic ring. The zone of peaks in the range 1000–1250 cm−1 reveals the C-N and the N-H interactions in the amides [−1, the C-O stretching vibration at the range 1185–1347 cm−1 and the O-H bending bond at 988 cm−1 [The FTIR spectrum of pure LH shows characteristic peaks of the N-H stretch bonds interacting at 3447 and 3382 cme amides . The sta988 cm−1 . FTIR sp988 cm−1 .The DSC thermograms of LH in the first heating cycle presented endothermic peaks responsible for melting (77.29 °C) and the region of degradation of the molecule  a,c,e,g . The staThe high viscosity often favors the prolonged release of the active substance from the hydrophilic gel via increase of its intrinsic friction, which influences the diffusion constant. This pattern was well preserved for the period of 2 h when the LH was released, with exemption of F3 formulation, which had an extremely high viscosity of almost 12,000 mPas. For this formulation, the pH was also diminished compared to the other samples. It may be proposed that the high viscosity and low pH of F3 correlated with the level of citric acid and temperature of preparation process, however the resulting release was a compromise. The low pH B could fThe observed phenomenon, when the F3 deviated from other samples in the terms of pH and viscosity, may be affiliated with structure of the used starch types. S1 and S3 contain characteristic intussusceptions A,B. ThisThe temperature of roasting as well as the level of esterification factor influence the prolongation of LH release from methylcellulose hydrophilic gel. The starch roasted at 140 °C more effectively favors the prolongation of the release of the LH compared to the starch pregelatinized at 120 °C. The phenomenon is most likely related to the spherical structure of the particles roasted at 140 °C, compared to the flatter and more differentiated structure of the 120 °C roasted starch. The influence is clearly observed when compared to methylcellulose gel without starch additive. Additionally, the content of citric acid favors the release prolongation. Increase in the concentration of esterification factor, citric acid, results in prolongation of the release of LH, both in the case of starch roasted at 120 °C and 140 °C; however, the prolongation is more noticeable only in the case of starch modified in the temperature of 140 °C (S4). In addition, S4, due to the higher pH values compared to S3, results in the formation of higher number of non-ionized forms of LH. The concentrations required to obtain prolonging effect overcame the level of 2% of modified starch in 2% methylcellulose in the case of starch roasted at 120 °C with 2.5% of additive of citric acid. The release prolongation was observed in formulations with 3% of modified starch in 2.5% methylcellulose hydrophilic gel. The kinetic models gave inconsistent interpretation, presumably due to the two-stage process of release, which will be further studied. The most visible results are provided by DSC analyses, which indicate the most stable LH formulation in the case of S1 and S3, starches roasted in 120 °C.


Brassica campestris L.) straw (RS), apple  tree branches (ATB), and pine (Pinus sp.) sawdust (PS), were carried out by pyrolysis under dynamic conditions (30 to 900 °C) at different heating rates of 5, 10, and 15 °C·min−1. Correlation analysis showed that intrinsic physicochemical properties play distinct roles in different stages of pyrolysis. The ash content was negatively correlated with the temperature range (R2) of the second stage (190–380 °C) of pyrolysis. The lignin content and the amount of pyrolysis residues (RSS) were positively correlated. Kinetic triplets, including the activation energy (Ea), pre-exponential factor (A), and reaction model [f(α)], were obtained using different methods, including the Flynn–Wall–Ozawa (FWO), Freidman, Kissinger–Akahira–Sunose (KAS), and Starink methods. The mean activation energy (Ea[mean]) for RS, ATB, and PS calculated by the different methods ranged from 167.15 to 195.58 kJ·mol−1, 195.37 to 234.95 kJ·mol−1, and 191.27–236.45 kJ·mol−1, respectively. Correlation analysis of the intrinsic physicochemical characteristics and kinetic factors of agroforestry waste showed that the minimum Ea (Ea[min]) was significantly positively correlated with heat capacity (C0) and negatively correlated with thermal diffusivity (D). The Ea[mean] and the maximum value of Ea (Ea[max]) significantly positively correlated with the sum content of cellulose and lignin, indicating that the contents of cellulose and lignin determines the energy required for the pyrolysis process of agroforestry waste. The mechanism of degradation involves the diffusion model , the growth model (A4), and the geometrical contraction model (R3). These results indicate that the pyrolysis of agroforestry waste is a complex process due to the heterogeneity of its intrinsic physicochemical properties.To obtain a comprehensive understanding of the qualitative and quantitative effects of the intrinsic properties of biomass on its pyrolysis characteristics and assess the behavior of agroforestry waste, thermogravimetric analyses of three representative agroforestry wastes, namely rape ( X, NOX, CH4, and SO2, but also result in economic losses ), mean (Ea[mean]), and maximum (Ea[max]) values of Ea are shown in Ea[mean] values determined by the FWO, Friedman, KAS, and Starink methods during the conversion process of RS were 167.15, 195.58, 177.90, and 178.60 kJ·mol−1, respectively; those of the ATB were 195.37, 234.95 207.19, and 207.57 kJ·mol−1, respectively; and those of the PS were 200.58, 236.45, 191.27, and 201.53 kJ·mol−1, respectively. It is worth nothing that Ea[mean] values determined for the three types of biomasses were different, which could indicate that the thermal decomposition mechanism of the whole pyrolysis process was different. The Ea[min] and Ea[max] values were obtained from Ea[min] essentially occurred at the initial stage of pyrolysis, while the occurrence of Ea[max] was dependent on the feedstocks and the calculation model.The minimum  and negatively correlated with D (p < 0.05). High fixed C and C0 do not facilitate the start of biomass pyrolysis, but high thermal conductivity values are favorable to the start of biomass pyrolysis. Aup-Ngoen et al. noted that the rhizome biomass of cassava (Manihot esculenta) with high fixed C withstood more decomposition compared to the other types of biomass residues  and Ea[max] obtained by the FWO, Freidman, and Starink methods significantly positively correlated with the sum content of cellulose and lignin, indicating that the contents of cellulose and lignin determines the energy required for the pyrolysis process of agroforestry waste. It also confirmed that the Ea[max] during the pyrolysis process was caused by the simultaneous decomposition of cellulose and lignin, which requires a large amount of energy. The maximum activation energy values significantly negatively correlated with the contents of moisture, ash, N, and hemicellulose. The reason is that hemicellulose and the N-containing substances in biomass have a weak bond strength and are easily decomposed  values were significantly positively correlated with C0 and negatively correlated with D. The Ea[mean] and Ea[max] were significantly positively correlated with the sum content of cellulose and lignin, indicating that the contents of cellulose and lignin determine the energy required for the pyrolysis process of agroforestry waste.The (4)A value and several reaction models  involved in the pyrolysis process indicate that the pyrolysis of agroforestry waste is a complex process due to the heterogeneity of its intrinsic physicochemical properties.Vast variations in In this study, the effect of intrinsic physicochemical properties of agroforestry waste on its pyrolysis characteristics was comprehensively investigated. The results of the study showed that:In summary, based on these findings, it can be concluded that agroforestry wastes have good pyrolysis potential, and the pyrolysis of agroforestry waste is a complex process due to the heterogeneity of its intrinsic physicochemical properties. The qualitative and quantitative effects of these intrinsic properties on the pyrolysis characteristics and behavior obtained from this study will help researchers and agroforestry industries directly estimate pyrolysis rates and control the efficiency of the pyrolysis process.


When the stiffness of the MG and the LG were compared before and after the MFP, changes in the stiffness of the MG were significantly greater than those in the LG (p < 0.05). This signifies that the MG was more affected by the exercise-induced muscle fatigue than was the LG. The assessment of musculoskeletal tissue and its characteristics, before and after eccentric exercise, is crucial in the prevention of overuse injuries associated with repeated exposure to both low and high levels of force.Muscles are affected at the cellular level by exercised-induced fatigue, inducing changes in their stiffness. Examining muscle stiffness can improve the knowledge of various pathologic conditions, such as pain and injury. The objective of this study was to examine the stiffness of the medial gastrocnemius (MG) muscle and the lateral gastrocnemius (LG) muscle to determine the changes in stiffness, and to assess the differences in the stiffness between the MG and the LG, as affected by muscle fatigue measured using shear wave elastography (SWE) and a MyotonPRO after inducing muscle fatigue. A total of 35 healthy young adults participated in the study. The stiffness of the MG and the LG were assessed before and after a muscle fatigue protocol (MFP), which included three sets of 50 eccentric contractions of the calf muscles of the dominant leg, at rest, and at maximum voluntary contraction (MVC). The measurements were taken with SWE and the MyotonPRO simultaneously. Compared to baseline, the resting stiffness of the MG and the LG significantly increased immediately, 24 h, and 48 h after muscle fatigue ( Skeletal muscles are the most vital source of human body movements . To percThe prime synergists are the triceps surae muscle for plantar flexion, having dissimilar architectural properties, such as differences in fascicle length, pennation angle, and muscle length. In comparison, the gastrocnemius muscle crosses both the knee and ankle, being a two-jointed muscle, whereas the soleus is a single-jointed muscle . In mostDuring physical activities such as running and hopping, the MG and LG muscles show spring-like characteristics ,7. TissuThe center of pressure (COP) is defined as “the center of all the external forces acting on the plantar surface of the foot” . The bioEccentric muscle contractions are an important part of daily activities . UnaccusIn recent years, shear wave elastography (SWE) has evolved with favorable results in discovering and diagnosing pathological conditions of muscles ,20. The Although SWE is a reliable tool in measuring tissue stiffness, it has some limitations. It requires technical expertise and higher maintenance costs, which make it less suitable for wider clinical use ,19. The Therefore, the purpose of this study was to examine the effect of exercise-induced muscle fatigue and recovery in MG and LG stiffness using SWE and MyotonPRO and to visualize the differences in the levels of stiffness between the MG and the LG as affected by muscle fatigue.2 and 30 kg/m2 [A total of 35 healthy college students , with a body mass index (BMI) between 18 kg/m30 kg/m2 , were vo30 kg/m2 , a low-t30 kg/m2 . Partici30 kg/m2 . ParticiUpon arrival at the laboratory, the participants were asked to rest comfortably in a room with a normal temperature for 10 min to stabilize their body conditions. Before starting the experiment (baseline), their heights and weights were measured. The participants were instructed on how to contract their muscles, and they were asked to practice MVC for familiarization. All participants underwent a total of four measurements: at baseline, immediately after the MFP, 24 h after the MFP, and 48 h after the MFP . They weThe muscle fatigue protocol of the current study was adopted and modified from previous studies ,33. The An ACUSON S3000 ultrasound device  and a 9 MHz linear probe were used for SWE measurements. During the acquisition of the data, the probe was placed parallel to the muscle fibers and was positioned with a generous amount of coupling gel and very light pressure for 8–10 s on the muscle bellies of the targeted muscles. SWE generates both a color map overlay that represents a qualitative elastogram, as well as an objective stiffness measurement. The transducer was kept stationary for 8–10 s on the marked area of the muscles for the acquisition of the stiffness measurement. A total of 5 ROIs in each image was assessed, and the average of the 5 ROIs was recorded for further analysis. The elastographic images were developed using the colors red and blue. Good intra-rater reliability for the stiffness measurements of the muscles of the lower limb was demonstrated by previous research .The mechanical measurements of tissue stiffness were examined using a MyotonPRO . The probe was placed on the previously marked points of the MG and LG. The researcher placed the probe on the site of measurement, and the MyotonPRO completed the measurement. The impulse generated by the probe on the muscle lasts for 15 milliseconds, with a light mechanical force of 0.6 N ,36. The The MicroFET2 handheld dynamometer (HHD)  was used to assess the amount of force generated by the MG and LG before and after the MFP. It was also used during contraction of the MG and LG to standardize the force and to deliver biofeedback to the subjects. The HHD was firmly secured to a wall with adhesive Velcro strips to allow adjustments and stability. Handheld dynamometry has been shown to have good-to-excellent reliability in measuring isometric lower limb strength and power in healthy subjects .G Power 3.1.9.7 software  was used to determine the sample size. The alpha error probability and power were set at 0.05 and 0.90, respectively. The effect size was set at 0.25 based on Cohen’s effect size f, for a total of four levels of measurement . As a reStatistical analyses were performed using Statistical Product and Service Solutions software for Windows 8.1 . All data are presented as mean ± standard deviation (SD), and the Shapiro–Wilk test was used to test for normal distribution. The Friedman test was performed to assess changes in the stiffness of the MG and LG across all measurement time points at each muscle state (resting and MVC), as well as for strength. Wilcoxon signed-rank tests were used to assess the difference in stiffness between the MG and LG. The level of significance was set at α = 0.05.The general characteristics of the participants are presented in p < 0.05) in the MG and LG at rest. In the contraction phase, the MG showed a significant change in stiffness (p < 0.05), whereas the LG showed no significant change across all the measurement time points (p > 0.05).The differences in the stiffness of the MG and LG across all measurement time points at rest and during contraction are summarized in p < 0.05), respectively, as measured by SWE. The contraction stiffness in the MG was found to be statistically significant over time (p < 0.05), whereas the contraction stiffness of the LG showed no change (p > 0.05).In the MG and LG, a significant change in the resting mean stiffness was observed over time (p < 0.05), when measured using the MyotonPRO, whereas with SWE, no significant difference was seen between the two muscles at any of the measurement time points (p > 0.05). With both the instruments, there was a significant difference between the contraction stiffness of the MG and the LG (p < 0.05), both at baseline and immediately after the MFP (p < 0.05), with the MyotonPRO, but not with SWE. At 24 h after the MFP, the muscles showed no significant differences (p > 0.05), but, at 48 h, a significant difference was seen between the MG and the LG (p < 0.05), as obtained by both of the instruments (The differences are summarized in truments .p < 0.05). A significant decrease was seen from baseline (243.87 ± 46.54) to immediately after the MFP  although no other changes were recorded at 24 h and 48 h after the MFP.A significant change in strength was observed across all measurement time points , as well as to determine which muscle was affected more. We hypothesized that, after the MFP, the stiffness of the gastrocnemius muscle will change, both at rest and during MVC, and the MG will be affected more than the LG. Our results showed a significant increase in the stiffness of the MG and LG in the resting state as well as immediately, 24 h, and 48 h after the MFP, as compared to baseline; however, the stiffness of the MG significantly decreased during MVC across all measurement time points, whereas that of the LG showed no change.The baseline resting stiffness values of the MG and LG, as measured with both instruments in this study, were concordant with those reported in other studies ,19,33. IIn this study, the MG showed significant changes in stiffness during MVC, whereas the LG showed no significant change. With SWE, a significant decrease was observed from baseline to immediately after the MFP, whereas stiffness measured with the MyotonPRO showed a significant decrease from baseline to immediately after the MFP and 24 h after the MFP. An increase in stiffness was observed from immediately after the MFP to 48 h after the MFP, indicating the recovery of the muscle. This decrease in stiffness after exercise can be explained by the loss of MVC after the MFP, signifying that the muscles were fatigued. Muscle fatigue can be defined as an exercise-induced decline in the maximal force capacity of the muscles involved . When thExercise-induced pain and the action of the agonist and antagonist muscles are additional aspects to consider. Eccentric contraction is known to induce pain, fatigue, swelling, tenderness, and stiffness in muscles although the most common immediate effect is pain . Arendt-In addition, a further analysis was executed so as to observe the difference in the stiffness before and after exercise-induced muscle fatigue between the MG and the LG. The resting stiffness as measured using the MyotonPRO demonstrated that the LG had significantly greater stiffness than the MG at baseline, immediately post-MFP, 24 h post-MFP, and 48 h post-MFP. SWE, on the other hand, showed no significant difference between the two muscles across all of the measurement time points. Although at rest, stiffness of the LG was greater than that of the MG, but a larger change in stiffness was seen in MG across all the levels of measurement, which explains why the MG was affected more by fatigue than the LG.Several previous studies measured the stiffness between the MG and the LG using the MyotonPRO and reported greater stiffness of the LG, similar to the present study, but none of the studies observed differences between the muscles, nor did they focus on the reason for the greater stiffness of the LG at rest ,15,26,48Additionally, fiber orientation can affect the measurement of stiffness. The type of muscle fiber can be a potential factor that might affect stiffness, considering that type I fibers are stiffer than type II fibers. Nonetheless, this cannot explain the greater LG stiffness, as the percentage of the fiber type is the same in both of the muscles. In addition, the perimysium and endomysium can affect muscle stiffness at rest ,55. HencAt contraction, the stiffness of the MG was greater than that of the LG, but immediately after the MFP, the stiffness of the MG decreased significantly, which shows that the MG was fatigued. There can be various reasons that could denote that the MG was fatigued more during the MFP than was the LG in the present study. The physiological cross-sectional area of the MG is greater, as are the muscle volume and pennation angle, because of which, it generates more than 70% of the strength, twice as much as LG ,26,49,52During the MFP, only the ball of the foot was in contact with the ground, which formed the BOS throughout the exercise. The COP, during dynamic movement, normally moves from lateral (from heel) to medial (great toe) for stability and the maintenance of balance . If the The limitations of this study must be addressed. First, subcutaneous fat was not assessed while taking measurements with the MyotonPRO, and muscles covered with >20 mm subcutaneous fat may affect stiffness measurements ,51. SecoMuscle fatigue is a common phenomenon that affects both athletic performance and the performance of various other activities. In this study, the stiffness of the MG decreased, and that of the LG showed no change. Therefore, the measurement of stiffness can strengthen the understanding of muscle fatigue and the changes it causes to the muscle itself. The assessment of musculoskeletal tissue and its characteristics before and after eccentric exercises is crucial in the prevention of overuse injuries associated with repeated exposure to low or high levels of force. It can provide background information that is important for developing effective training strategies. Overall, the results of our study may have relevant applications for elite sports practice and for musculoskeletal rehabilitation.


Weight regain is a serious issue after bariatric surgery. Using banding for one anastomotic gastric bypass prevents weight regain, but carries the risk of band erosion. The combination of bariatric procedures and fundoplication for patients without hiatal hernia probably prevents weight regain. However, no studies are demonstrating this.A 38-year-old woman who underwent laparoscopic one anastomosis gastric bypass with fundoplication of remnant stomach maintained a stable body weight after 5 years.Owing to the complications associated with the conventional methods, the combination treatment has several advantages such as prevention leak of suture line in the gastric pouch prevention.The combination treatment could successfully prevent weight regain and thus, will be helpful in the better management of obesity. •The combination of bariatric treatment prevents weight regain, bile and acid reflux.•Complete coverage of weak site by the fundoplication wrap for better safety•Advantages of FundoRingOAGB over Nissen fundoplication can be listed. We carried out laparoscopic one anastomosis gastric bypass (OAGB) with fundoplication of the remnant stomach in a patient without hiatal hernia with a 5-years follow-up. This report is in line with the Surgical CAse Report (SCARE) criteria 22.12] was followed-up at our bariatric clinic after 5 years of the surgery. There was no history of medications or smoking. The family history involved obesity in both parents.A 39-year-old woman with a history of laparoscopic mini-gastric bypass with a fundoplication for morbid obesity [body mass index (BMI) 41.4 kg/mDuring the operation, a hiatal hernia was not observed. However, due to the complaint of heartburn, a one-stage fundoplication was performed.2.2The procedure was performed by a certified bariatric surgeon with more than 10 years of experience in gastric bypass surgery.The overview of the surgical procedure is shown schematically in In the beginning, we laparoscopically performed the standard gastric pouch for one anastomosis gastric bypass The dissection of short gastric vessels increased the mobilization of the fundus of the stomach. This leads to its free movement through the retrogastroesophageal canal under the intra-abdominal segment of the esophagus (3/4 part of wrap) and under the upper part of the gastric pouch (1/4 part of wrap) A, B.Fig.As in standard Nissen fundoplication, we sewed the anterior and posterior parts of the fundoplication wrap with non-absorbable Etibond 2/0 sutures. However, unlike the Nissen method, we used a staple suture line of stomach during the procedure. To improve the reliability of the seam, the staple suture line of the gastric pouch was covered and nestled inside the anterior part of the wrap a.Fig. 4Sa)for the creation of the posterior part of the wrap we captured the widely mobilized fundus in the upper part of the staple line of the remnant stomach and was passed behind the intra-abdominal segment of the esophagus from left to right. This step was performed after the left and right crural dissection and opening of the gastrohepatic ligament beginning at the pars flaccida.b)the upper edge of the stapler suture line of the gastric pouch was simultaneously stitched to the lower part of the wrap between the anterior and posterior parts to prevent slipping of the wrap and for the correct functioning of the anti-reflux mechanism b.Besides, unlike the standard Nissen fundoplication:Moreover, unlike the Nissen method, we stitched the edges of the wrap at the 1 o'clock position on the anterior aspect of the esophagus (not at 10 o'clock as in the Nissen method) The anterior part of fundoplication was extended downwards, along the stapled suture line of the gastric pouch, for approximately 2 cm for the creation of additional partial fundoplication. Thus, we created an upper: total fundoplication around the intra-abdominal segment of the esophagus and lower: a partial fundoplication to the left of the stapled line of the gastric pouch. For calibration, we used a gastric bougie of size 32 Fr.The next difference is the additional suturing between the anterior and posterior parts of the fundoplication wrap at 3 o'clock to form a “live ring” (“FundoRing”) A, B.Fig.Subsequently, the routine surgical technique of OAGB was followed. A jejunal loop measuring 200 cm from the ligament of Treitz was anastomosed to the gastric pouch. The two-layer hand-sewn 2 cm gastrojejunostomy was created by using absorbable sutures (Vicryl 2/0) (Ethicon).The anastomosis was tested using methylene blue injection, and the port sites were subsequently closed using the standard closure techniques.2.3The patient received an intravenous infusion with antibiotics before the procedure and for 1 day after the procedure. The proton pump inhibitor was administered over 24 h and then taken orally for 6 weeks. The patient started a clear liquid diet on the 1st postoperative day. The patient was discharged on the 3rd postoperative day with adequate diet tolerance.2.42 before surgery. After surgery, the BMI were 25.6 kg/m2, 23.1 kg/m2, 24.1 kg/m2, 24.3 kg/m2 and 25.4 kg/m2 after the first year to the fifth year respectively. After 5 years, the patient expressed his satisfaction with the results of the procedure.The follow-up was carried out every year up to 5 years after the surgery. We evaluated the body mass index before the surgery and during the follow-up . The BMI3Various bariatric interventions such as hypocaloric diet therapy and gastric bypass are being used for the management of obesity. Compared to the hypocaloric diet therapy, gastric bypass resulted in greater body mass loss and greater metabolic syndrome resolution, but none of these interventions have an anti-reflux component, such as a fundoplication Moreover, the gastric bypass has a high incidence of complications such as dumping syndrome, reflux esophagitis, and recurrence of obesity. Therefore, there has been an increase in the popularity of combined bariatric procedures and fundoplication for revisional bariatric surgery.We have proposed a classification of combination procedures wherein we have presented a novel combined method called “FundoRingOAGB” 1.Complete anatomical separation of the fundus of the stomach by dissecting the short gastric vessels of the fundus facilitated tension-free and wide fundoplication around the intra-abdominal segment of the esophagus and upper part of the gastric pouch.2.Complete coverage of the area that is susceptible to leak of suture line in the gastric pouch in the upper part increases the safety.3.Demonstrating the possibility of extension of fundoplication downwards along the stapled line of the gastric pouch as an additional partial Fundo(gastro)plication.4.It is possible to correct the tension of the wrap using calibration. The covering of the suture line of the gastric pouch by the lower surfaces of the fundoplication wrap according to the type of a living ring.5.A wide and calibrated wrap around the gastric pouch prevents its dilatation and gaining of weight in the late postoperative period.6.The combination of one anastomosis gastric bypass with fundoplication of the remnant stomach can be applied not only to prevent weight regain but also for the prevention of biliary reflux and acid reflux.For the first time, we would like to highlight the advantages of FundoRingOAGB over the conventional Nissen fundoplication:The preliminary data of this clinical case showing promising outcomes led us to the initiation of a randomized controlled trial to further validate the results 4The combination of one anastomosis gastric bypass with fundoplication of the remnant stomach is effective and could be used for better management of obesity.Written informed consent was obtained from the patient and her family for the publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor in Chief of this journal upon request.Not commissioned, externally peer-reviewed.Not applicable.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Oral Ospanov.ClinicalTrials.gov identifier: NCT04834635.Oral Ospanov is the corresponding author and conceptualized of treatment and the manuscript.Kamalzan Nadirov, Vitaly Koikov, and Nurlan Zharov contributed to play important role to data collection, data analysis, interpretation, and writing the paper. Oral Ospanov, Kamalzan Nadirov, Vitaly Koikov, and Nurlan Zharov approved the final manuscript.All authors declare no conflicts of interest.


The study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface.A monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface  between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed.n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002).Eleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months  after surgery.Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months  peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival. The introduction of Descemet Membrane Endothelial Keratoplasty (DMEK) into clinical practice in 2006 has considerably advanced surgical treatment of Fuchs endothelial corneal dystrophy, bullous keratopathy, and other corneal endothelial diseases . This haIn comparison to penetrating keratoplasty (PK), DMEK leads to faster visual rehabilitation, does not always require corneal sutures, has a lower surgically induced astigmatism, and lower risk of immunological rejection. Therefore, DMEK could be considered the technique of choice in patients with endothelial graft failure after PK, e.g., if uncorrected or spectacle-corrected vision was good prior to graft failure, and/or in patients with higher risk of rejection, and/or in patients with ocular surface disorders . This apSeveral studies have shown feasibility and favorable results of posterior lamellar keratoplasty  or DMEK) in patients with failed PK , 6–11. RA monocentric, retrospective review of all patients with endothelial graft failure after PK treated with oversized DMEK grafts and descemetorhexis outside of the PK interface in host tissue between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed. The study was approved by the ethics committee at the University of Düsseldorf (study number: 2020–1014).All procedures were performed under general anesthesia. Donor tissues were organ cultured and provided from either LIONS eye bank  or ETB-Bislife . Tissue preparation was performed immediately before the actual operation by the surgeons without any marking. Paracentesis and an anterior chamber (AC) maintainer were used to achieve complete air fill of the AC. The host’s DM was scored within the host’s tissue, that is, peripheral to the graft-host interface using a Price hook. In a recent published case report by the authors successful stripping per continuitatem without tearing the DM interface of host and PK donor can be seen in a supplemental video . Air wasThe diameter of all DMEK grafts exceeded the diameter of previous PKs. Mean diameter of the previous PK was 7.73 ± 0.2 mm (range from 7.25 to 8 mm). Diameter of the DMEK grafts was 8.25 mm. Mean overlap was 0.52 ± 0.2 mm (range from 0.25 to 1 mm). Individual sizing characteristics are shown in Table Postoperatively, dexamethasone 1 mg/ml and ofloxacin 3 mg/ml unpreserved eye drops were administered five times daily for 1 week. Antibiotic drops were then discontinued and dexamethasone drops tapered monthly to once daily. Prednisolone acetate was administered systemically (1 mg/kg per day) postoperatively and tapered every 3 days over 3 weeks.Successful DMEK was defined as a clear cornea at 3 months after transplantation. Primary graft failure was defined as an absence of corneal clearing after the surgery or recurrence of corneal edema with loss of visual acuity within 3 months after surgery. Graft rejection was defined as new signs of graft rejection like anterior chamber flare/cells, Khodadoust line, or keratic precipitates which could not be explained otherwise.t-test (BCVA and CCT) was used. The p-values under 0.05 were considered statistically significant.Patient characteristics, number of previous corneal transplants in the eye receiving a DMEK, size of previous PK, size of DMEK graft including size of descemetorhexis, intraoperative and postoperative complications including rebubbling or graft rejection, best corrected visual acuity (BCVA), and central corneal thickness (CCT) were collected. CCT was measured using Scheimpflug tomography . Data for endothelial cell density (ECD) were available in three cases and were measured with specular microskopie . Baseline donor endothelial cell density was measured with phase-contrast microscopy . All data were recorded and analyzed using Microsoft Excel (2011 for Mac OS). For statistical significance testing, paired n = 5 eyes, 45.5%), followed by keratoconus . Two of patients were operated because of corneal scarring . In one patient due to herpetic keratitis, in the other one the reason for corneal scarring remained unclear.Eleven eyes from ten patients were included in this study. Seven patients were female, four male. Mean age was 69 ± 7.5 years . Main indication for the first PK graft was Fuchs endothelial corneal dystrophy (Mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). On average, 1.7 ± 1.0 previous PKs had been performed per eye (range 1 to 4). The cause of endothelial cell failure after PK was late endothelial cell failure in eight eyes (72.7%) and immunologic rejection in three eyes (27.3%).n = 3 eyes, 27.3%). All of these patients suffered from glaucoma. From these patients, one had previous filtration surgery, and one patient multiple cyclophotocoagulation.More than one quarter of all patients had preoperative comorbidities limiting preoperative and postoperative visual acuity . Figure n = 11). Visual acuity increased by 5 lines from 1.24 ± 0.5 logMAR (range 0.2 to 2) to 0.73 ± 0.76 logMAR (range 0.1 to 2) within 3 months (p = 0.006) and remained stable until last follow-up 16.7 ± 11.6 months postoperatively . Due to patients without visual potential and failed transplants, standard deviation is high.Figure p < 0.001) to 0.31 ± 0.2 logMAR (range 0.1 to 0.7) and remained stable without significant chances by 6 months at 0.35 ± 0.19 logMAR  and by 12 months at 0.29 ± 0.12 logMAR . Both improvements were significant compared to preoperative BCVA (p6 months/12 months < 0.001). Mean BCVA at the last follow-up 15.1 ± 11.4 months postoperatively (range from 6 to 39 months) was 0.29 ± 0.12 logMAR .Disregarding failed transplants and patients without visual potential with central visual field defects because of glaucoma BCVA improved substantial. Eight eyes were included in this analysis. Mean preoperative BCVA in this cohort was 1.06 ± 0.48 logMAR (range 0.5 to 2). Visual acuity significantly improved by 3 months by a mean of 8 lines .Data of central corneal thickness were available for 72.7% of the patients during follow-up . One of these patients developed persistent graft detachment with primary graft failure despite rebubbling, but refused further interventions, particularly the necessary repeated rebubbling.2 (range from 2482 to 2628). Mean endothelial cell density was 1375 ± 415 cells/mm2 (range from 897 to 1634) 17.3 ± 9.9 months (range from 6 to 24 months) after surgery.Endothelial cell density could only be reliable measured with a specular microscope in three cases. Baseline donor endothelial cell density was 2555 ± 73 cells/mmDMEK is a therapeutic option for patients with endothelial graft failure after PK. Although the speed of visual recovery compared to regular DMEK is slower, the advantages are considerable. These include faster visual rehabilitation, lower surgically induced astigmatism, lower risk of immunological rejection, and absence of long-lasting corneal sutures . Known dDespite these potential advantages, the surgical technique for DMEK in patients after PK regarding DM stripping and diameter of the graft is still under debate. Stripping could be performed inside the old PK graft, at the interface or in the recipient, peripheral to of the previous PK. Each variant is associated with specific advantages and disadvantages. A smaller descemetorhexis by stripping inside the previous PK followed by a smaller DMEK graft is associated with lower numbers of transplanted endothelial cells. Stripping within the interface leads to adapted wound edges may improve tissue healing, but has the disadvantage of risking opening the stromal interface and may lead to dehiscence or even perforation. Decemetorhexis in the host tissue  favors the use of oversizing DMEK graft but carries the risk of aggravated intraoperative course, e.g., due to strong attachments at the interface and possibly lead to piecemeal removal. A larger graft — compared to the host cornea — and thus more donor EC might help endothelial survival . Indeed A recently published retrospective study by Pasari et al. showed a higher rebubbling rate when the diameter of the DMEK was oversized compared to the previous PK. The authors speculated that this was due to posterior irregularities in the transition zone of host and PK graft. However, in contrast to our study, in the report by Pasari et al. stripping was performed within the edge of the PK wound . It has Our study shows that DM stripping outside the PK interface is surgically feasible and allows the stripping of a larger posterior corneal surface. This in turn is the prerequisite for using larger DMEK grafts with more endothelial cells Fig. .Fig. 4AnA major limitation of our study is a relatively small cohort of 11 patients, the retrospective aspect of our study, and the lack of ECD measurements for each patient. Therefore, our study cannot prove that prolonged graft survival can be achieved by an oversized graft. Moreover, due to the lack of a control group with grafts of the same size or smaller, it cannot be shown that this surgical technique leads to better results in our hands.Further studies are required to determine whether preoperative or intraoperative visualization  of the transition zone of the previous PK may help to detect less favorable preoperative conditions , which are likely to prevent successful stripping outside of the transition zone and graft attachment Fig.  17]. An. An17].


This work reviews the literature regarding spontaneous closure of idiopathicfull-thickness macular holes (FTMHs).Literature on patients with spontaneous idiopathic FTMH closure was reviewedvia Ovid MEDLINE, EMBASE, and PubMed through July 16, 2020. A total of 27 of66 identified articles were included.A total of 68 eyes had spontaneous closure. Of the patients, 62.7% were womenand the average age was 67.5 years. Visual acuity improved from Snellen20/78 to 20/33 post closure. The average hole diameter was 176.8 μm; thelargest was 350 μm. Most were stage 2 according to Gass and of small sizeaccording to International Vitreomacular Traction Study Group (IVTS)staging. The predominant classification system in recent literature is IVTSstaging. The average optical coherence tomography–observed closure time was4.5 months.On review, reported spontaneous closure rates of all idiopathic FTMH rangefrom 3% to 15%, and no demographic subgroups are more likely to haveclosure. Holes ≤250 µm have higher closure rates (22.2%) than those in therange of >250 to 400 µm (13.3%) and ≥400 µm (0%). Closure is associatedwith favorable visual outcomes, and retinal bridging via glial cells islikely critical to closure. These determinations were based on limitednumbers; prospective studies are needed to further ascertain rate,mechanism, and characteristics. IVTS staging provides reliable reporting andinsight into whether FTMH can be observed before surgery. Full-thickness macular hole (FTMH) is defined by an opening through alllayers of the retina that develops at the fovea. Disruption of the macula and foveacauses debilitating visual symptoms including decreased central visual acuity (VA),metamorphopsia, and central scotoma. Holes are mostly idiopathic, also known asprimary, but may be secondary to trauma or macular edema. Idiopathic FTMHs are age related, typically affecting older women, butunrelated to ocular or systemic conditions.Macular hole was described 150 years ago by Knapp and initially classified by Gass. However, idiopathic FTMH may reportedly close spontaneously, promptingdiscussion regarding prolonging the observation period to see whether closure occurswithout surgery. Spontaneous closure of idiopathic FTMH is less common than that in secondarytraumatic holes but more common than in myopic holes, which rarely close spontaneously. Hole-closure incidence, factors influencing closure, closure mechanism, andpostclosure outcomes all remain controversial.First-line treatment is vitrectomy, which is safe and effective. Surgery isrecommended for macular holes stage 2 and beyond based on Gass classification. Thus, it is important to consolidate our understanding of spontaneous closurebased on the literature in a modern classification context. In this review, wesummarize the literature regarding spontaneous idiopathic FTMH closure in terms ofincidence, clinical characteristics, outcomes, and mechanisms.Optical coherence tomography (OCT) has made the classification, diagnosis, andobservation of idiopathic FTMH more precise via enhanced visualization of retinallayers through high-resolution cross-sectional images.A systematic literature search of Ovid MEDLINE, PubMed, Embase Classic, and theupdated Embase database was performed July 16, 2020. There were no yearrestrictions. Only English-language articles were included. The search strategywas “idiopathic” and “macular hole” and “spontaneous,” which yielded 66 results.After full-text screening of the results and their references, 27 studies werereviewed. Studies were included if they reported 1 or more cases of spontaneousidiopathic FTMH closure with a detailed description of clinical characteristicsincluding patient age, sex, hole size, and hole classification. Studies withoutOCT were included, but separately analyzed, to support analysis of clinicalfactors that may be associated with spontaneous closure but did not factor intothe closure rate assessment based on hole size. Exclusion criteria were historyof ocular surgery in the affected eye, or any intervention in the affected eyeat any time from hole diagnosis to resolution. The first was a biomicroscopic 4-stage system introduced by Gass. After the advent of OCT, there was an era of OCT descriptions of holesused with the Gass system, leading to unstandardized OCT-modified Gass staging.Altaweel and Ip summarized an OCT-modified Gass staging system that was used before theInternational Vitreomacular Traction Study Group (IVTS) system was established.In 2013, the IVTS Group proposed a consensus of an OCT-based classificationsystem for diseases of the vitreomacular interface, including macular holes. Inaccordance with IVTS classification, our size-based subgroup analysis wasdivided into small (≤250 μm), medium (>250-400 μm), and large (>400 μm) holes.Holes were divided for subgroup analysis based on stage and size via establishedstaging systems . Reports from before the IVTS classification was established used Gass (19eyes) or OCT-modified Gass (27 eyes) classification, with OCT-modified Gassbeing more common. Since 2013, every included study (11 eyes) used the IVTSclassification, providing improved reporting consistency . The retrospective study with the higher closure rate of 3.5% of 142 eyeshad a longer observation time of 80 days compared with 60 days in the studyreporting a closure rate of 2.7% of 510 eyes, suggesting waiting time influencesreported rates. Definitive hole closure may not occur until 3 months after the process begins.Since OCT has made hole diagnosis and closure verification more reliable, a ratereappraisal was warranted. Four studies observed closure rates with OCTmeasurements, 2 of which were retrospective case series and 2 of which wererandomized controlled trials (RCTs). Combined, the retrospective studiesreported a cumulative closure rate of 2.9% of 652 eyes, and the RCTs had acumulative closure rate of 12.3% in a total of 73 eyes .The RCTs were the Ocriplasmin for Treatment for Symptomatic VitreomacularAdhesion Including Macular Hole (OASIS) Trial and Microplasmin for IntravitreousInjection–Traction Release Without Surgical Treatment (MIVI-TRUST) studies; bothreports examined the efficacy and safety outcomes of ocriplasmin treatment forsymptomatic vitreomacular adhesion/traction including FTMH. They providedvaluable prospective, long-term, OCT-based data on spontaneous closure rates viatheir sham groups. The sham group of the OASIS trial had no intraocularintervention whereas the MIVI-TRUST studies included sham injection of a vehicleinto the vitreous space, so these studies may not be comparable because of theeffect of intravitreal injection itself on the vitreous. Closure rates may have been underestimated because of follow-up bias, aspatients may have had spontaneous closure without attending follow-upappointments or seeking medical care. Thus, larger prospective OCT-based studieswith a standardized observation period length should be conducted to elucidateaccurate estimates of closure rate.The OASIS trial reported a closure rate of 15.4% of 26 eyes by month 3, whichremained unchanged by month 24, whereas the MIVI-TRUST studies reported aclosure rate of 10.6% of 47 eyes by month 6. The prospective studies had cumulative closure rates of 18.6% in 43 stage2, 7% in 28 stage 3, and 0% in 9 stage 4 holes. In addition, in our review of cases with Gass staging, most closed holeswere stage 2 . The retrospective studies together reported cumulative closure rates of3.1% in 97 stage 2, 0% in 121 stage 3, and 0% in 56 stage 4 holes. stage 2 . This su Additionally, 2 retrospective studies measuring the size of spontaneouslyclosed holes showed that 18 small (≤250 μm) and 1 medium (>250-400 μm) holeclosed spontaneously. Most of the 41 spontaneously closed holes with OCT-based size informationin our review were small, some were medium, and none were large . Combined, their shamgroups indicated a spontaneous closure rate of 22.2% in 36 small, 13.3% in 30medium, and 0% in 7 large holes.arge see . Also, iarge see . This su In our review, average OCT-observed closure time was 4.5 ± 4.9 months  see . Medium-ths) see , thus Ga It commonly presents in the sixth and seventh decades of life. Incidence of bilateral macular holes reportedly ranges from 0% to 7% onpresentation and 0% to 28% during follow-up, which itself ranges from 19 to 57 months. There is no consensus regarding characteristics of patients who havespontaneous closure. In our review, the mean age of such patients was 67.5 ±8.35 years , 62.7% were women, and 7.6% had bilateralidiopathic FTMH  for all 68 eyes was0.59 ± 0.33 logMAR , Snellen 20/78 ± 43 . The average BCVA post closure was 0.22 ± 0.20 logMAR, Snellen 20/33 ± 32 .The average change in BCVA was –0.37 ± 0.27 logMAR (range –1.3 to 0.12 logMAR),18.5 ± 13.8 Early Treatment Diabetic Retinopathy Study (ETDRS) . For 18 eyes with reported final BCVA, the average was 0.11 ± 0.11 logMAR, Snellen 20/26 ± 26 see . TwoeyeUsing the Gass classification, stage 3 holes were associated with better initialand postclosure BCVA than stage 2 and 4 holes, but holes across all stagesdemonstrated similar BCVA improvement. Using IVTS classification, small andmedium holes had similar initial and postclosure BCVA, as well as similarimprovement in BCVA; however, subgroup assessment of VA outcomes was limited bysample size for IVTS-classified holes see . Further The most important factor for VA improvement appears to be integrity ofthe inner segment–outer segment junction, also known as the ellipsoid zone (EZ).If there is no regeneration within the EZ, VA remains unchanged even on closure. The PR layer defect caused by a hole usually resolves over time. One study examining long-term outcomes of macular microstructure inspontaneous closure showed complete recovery within 3 years. Delayed EZ linerecovery may be associated with larger minimal hole diameter and incomplete VArecovery post closure. Also, persistent foveal detachment was associated with larger basal holediameter and incomplete VA recovery post closure, which may explain a linkbetween hole size and VA outcome.Photoreceptor (PR) layer structure is an important predictor of VA in spontaneousclosure, because disruption of the PR layer may lead to poorer VA outcomes.Closure time has been shown to have a significant negative correlation withsymptom duration and a positive, albeit nonsignificant, correlation withpostclosure VA, which reinforces that patients should be educated to seekmedical attention as soon as possible if they experience blurry vision ormetamorphopsia. Furthermore, complete posterior vitreous detachment may resultin better VA, probably owing to vitreomacular traction release. Subsequently, the Moorfields Macular Hole Study Group RCT demonstrated an11.5% spontaneous closure rate and a significant VA benefit of vitrectomy overobservation at 3, 12, and 24 months of follow-up for 185 Gass 2, 3, and 4 holes. However, neither study reported a subgroup analysis of spontaneousclosure outcomes, possibly owing to their small sample sizes. Therefore, largeprospective studies comparing visual outcomes of spontaneously closed withsurgically closed idiopathic FTMH are needed before recommendations can be maderegarding observation before surgery.Although an observation period to allow for possible spontaneous idiopathic FTMHclosure while avoiding undergoing surgical closure has been suggested, it isimportant to compare the outcomes of spontaneous closure with vitrectomy beforerecommending observation. The Vitrectomy for Macular Hole Study Group RCTdemonstrated a 6.6% spontaneous closure rate and did not show significant VAbenefit of vitrectomy over observation at 6 months of follow-up for 165 Gassstage 2, 3, or 4 holes.Given the improved visual outcomes when surgery is performed early while patientshave better VA, most surgeons may continue to advocate for promptly proceedingwith surgery rather than risking vision decline while waiting for the smallpossibility of spontaneous closure. Future studies could guide recommendationsregarding observation duration by uncovering predictive structural features, inaddition to small size, that suggest whether a hole is more or less likely toclose. Bridging may allow resolution of cystoid spaces by preventing influx ofvitreous fluid into intraretinal spaces. Bridging has been proposed to be initiated by irregular macular holeedges, possibly making such holes more likely to close. One study reported obvious sharp edges in 69% of 39 OCT scan images ofspontaneous closure. No studies demonstrated closure without bridging. This suggests bridgingis an essential part of closure, which has been hypothesized previously. Although there is debate regarding which cells proliferate, it is mostoften proposed to be glial cells—specifically Müller cells—rather thanalternatives including retinal postmitotic neurosensory cells or retinal pigmentepithelium cells.The mechanism of spontaneous closure remains elusive, although several have beenproposed .The mos A few studies demonstrated closure without detachment, suggesting it is unnecessary. Furthermore, some studies showed that the posterior hyaloid was alreadycompletely detached upon presentation, meaning there was no traction to be released. Consequently, posterior hyaloid membrane detachment may facilitateclosure but is not required.Another proposed mechanism is posterior hyaloid membrane detachment from thefovea to release vitreomacular traction. However, this is inconsistentlyreported. Only some cases in our review supported this mechanism. Like posterior hyaloid detachment, an ERM may assist in closure but isnot crucial. Therefore, bridge formation seems critical to spontaneous closure,posterior hyaloid detachment is a common occurrence that may promote closure,and significance of ERM is undetermined.Formation and circumferential shrinkage of a contractile ERM closing the hole bypulling its edges together is the third proposed mechanism. Ten eyes in ourreview had an associated ERM.The rate of spontaneous idiopathic FTMH closure across all stages and sizes is around3% based on 2 large OCT-based retrospective case series but more than 10% based on 2OCT-based RCTs, which are more reliable than previous studies without OCT.Spontaneous closure is associated with favorable VA outcomes, with early recovery ofthe EZ line being the most important factor. There is evidence supporting variousspontaneous closure mechanisms, but retinal bridge formation via glial cells is themost supported by OCT-based observations. However, much remains to be explored aboutrate, visual outcomes, and mechanisms of spontaneous closure due to absence ofhigh-level evidence regarding these topics. Future prospective studies based on OCTand multimodal imaging with standard observation periods might address the manyquestions surrounding spontaneous idiopathic FTMH closure.Holes in earlier stages based on Gass or OCT-modified Gass staging, or of smallersize based on IVTS classification, are more likely to close. Although Gassclassification is widely used clinically, IVTS staging provides greater reliabilityin practice to define the clinical characteristics of macular hole presentation andshould be widely adopted. Prospective studies using IVTS classification demonstratea closure rate of 22.2% in 36 small (≤250 μm), 13.3% in 30 medium (>250-400 μm),and 0% in 7 large (>400 μm) holes. Prompt surgery remains the first-linetreatment in all holes, regardless of size, because of the absence of comparativeprospective studies that ensure visual outcomes from spontaneous closure followingobservation are as favorable as surgery.Click here for additional data file.Supplemental Material, sj-docx-1-vrd-10.1177_24741264211049873 for SpontaneousClosure of an Idiopathic Full-Thickness Macular Hole: A Literature Review byAnubhav Garg, Brian G. Ballios and Peng Yan in Journal of VitreoRetinalDiseasesClick here for additional data file.Supplemental Material, sj-docx-2-vrd-10.1177_24741264211049873 for SpontaneousClosure of an Idiopathic Full-Thickness Macular Hole: A Literature Review byAnubhav Garg, Brian G. Ballios and Peng Yan in Journal of VitreoRetinalDiseases


Naunyn-Schmeideberg’s Archives of Pharmacology is the oldest pharmacology journal, founded in 1873 by Bernhard Naunyn, Oswald Schmiedeberg, and Edwin Klebs  being the language of science at that time , 120 pupils and students from 20 different countries of the world came to study under his guidance. Schmiedeberg trained many students so successfully that they later became professors at other German universities and in several foreign countries including the UK, the USA, Italy, Austria, Switzerland, Norway, and Japan  continued to promote the journal by offering fair and constructive peer review  flooded the journal Seifert . But thrNaunyn–Schmiedeberg’s Archives of Pharmacology does not strive to publish research that will be the ultimate basis for a Nobel Prize, but the journal will remain open-minded for every solid research paper in the broad field of pharmacology. We explicitly welcome research from smaller fields of pharmacology with only a small (current) community. Experience has shown that it may take decades until the full scientific importance of research data, initially perceived as “marginal” by protagonists, is recognized (Seifert and Schirmer Naunyn–Schmiedeberg’s Archives of Pharmacology from a “neurotransmitter” journal into a pharmacological journal that now covers many more research topics than 50 years ago (Dats et al. For journal editors, it is not easy to precisely foresee the future of a journal and the content of future submissions. The legacy of Oswald Schmniedeberg is to have a broad and open-minded approach to pharmacology. His multiple research interests were extremely useful for the future development of different specialized research areas both in academia and the pharmaceutical industry (Philippu and Seifert Genomics refers to the study of the entirety of an organism’s genes, called the genome, including interactions of those genes with each other and with the person’s environment. Genomics emerged in the 1980s and developed with the start of the Human Genome Project, which took 20 years and was completed in 2003, although more than a decade later genomics is still big business. The postgenomic era has made a drastic shift in research methodology. The biological methods for knowledge elucidation and pharmacological approaches to biomarker discovery have been rapidly changed in the postgenomic era. Postgenomics is transforming our understanding of disease and health. Indeed, differential expression of proteins in health and disease holds the key to early diagnosis and accelerating drug discovery. Our improved biomedical knowledge and understanding in the postgenomic era have led to advances in molecular and cellular biological research in the field of pharmacology. The science of pharmacology, which makes use of multi-disciplinary approach in looking into the reciprocal interactions of chemicals on biological systems, can place these advances in the appropriate physiological context of organ systems and intact animals.Naunyn–Schmiedeberg’s Archives of Pharmacology has faced a major turning point. Naunyn–Schmiedeberg’s Archives of Pharmacology has published many papers with the use of molecular biology techniques and genetically modified or transgenic animals. While the publication of the submissions which are descriptive and lack mechanistic novelty has been limited, Naunyn–Schmiedeberg’s Archives of Pharmacology has spared no effort to pick up papers covering research on the role of cellular signal transduction in pharmacology and toxicology.Entering the postgenomic era, Naunyn–Schmiedeberg’s Archives of Pharmacology will not only further develop the traditional areas of strength for the journal, including neuropharmacology, cardiovascular pharmacology, and more recently, immunopharmacology and tumor pharmacology (Dats et al. Naunyn–Schmiedeberg’s Archives of Pharmacology should expand and enhance the roles of editorials and reviews in the journal. Editorials are defined as an opinion or a view of a member of the editorial board or any senior or reputed faculty written in a journal and may be a commentary on a published article or a topic of current interest which has not been covered by the journal (Nundy et al. Naunyn–Schmiedeberg’s Archives of Pharmacology will continue to play a vital role in providing a place for communication of state-of-art-research on all aspects of pharmacology and its contribution to human health and to seek feedback from our authors and readers on different ways to further develop the journal and greatly advance the field of pharmacology.In the future,


This article  has beenPLOS ONE Editors issue this Expression of Concern.PLOS will be investigating these concerns in accordance with COPE guidance and journal policies. Meanwhile, the The journal has been informed that third author CD is deceased.