Cognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface‐shape patterns to verbal and visual learning.We analyzed hippocampal surface shapes on high‐resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age‐ and sex‐matched healthy volunteers.p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE , whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline.Both left TLE (LTLE) and right TLE (RTLE) patients had lower verbal  and visual learning  scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; ANN NEUROL 2020;88:170–182Memory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020  Temporal lobe epilepsy (TLE) is the most frequent form of chronic focal epilepsy in adults, with up to 70% of TLE patients suffering from declarative memory problems.First, how strongly are memory functions lateralized in TLE? The traditional material‐specific model states that verbal deficits are usually observed in epilepsy affecting the dominant  hemisphere,Second, why do some patients with TLE have memory impairments whereas others do not? Most cognitive difficulties are already detectable at or even before the onset of seizures, suggesting an important role of the underlying structural and cellular pathology.Lastly, is there a subregionally specific contribution of the hippocampus to verbal and visual memory formation? Various quantitative histology studies have assessed neuronal cell counts on hippocampal specimens obtained during temporal lobe resections but produced conflicting findings Table .10, 11, Histological neuronal cell counts have 2 major limitations. Histopathology only evaluates tissue from a limited number of slices of the hippocampus, restricting the method's ability to make spatial inferences on the location of the findings. Additionally, the contralateral hippocampus cannot be investigated.To overcome some of these limitations, we analyzed alterations of hippocampal morphology using noninvasive surface shape analysis on high‐resolution MRI,We identified consecutive TLE patients undergoing epilepsy surgery at the National Hospital for Neurology and Neurosurgery  and 39 age‐ and sex‐matched healthy volunteers. The details of our ongoing epilepsy cohort study have been described previously.In addition, we included a validation set of 55 independent unilateral refractory TLE patients  evaluated at NHNN and meeting the criteria described above.The standard ATLR consisted of the removal of the temporal pole and opening of the temporal horn, followed by en bloc resection of the hippocampus with a posterior resection margin at the midbrainstem level. Typically, the anterior–posterior extent of the temporal lobe resection as measured from the temporal pole to the posterior margin of resection is 30% and 35% of the distance from the temporal pole to the occipital pole after left and right ATLR, respectively. Only the anterior part of the hippocampus is resected during this procedure, and parts of the body and the tail remain as a postsurgical remnant.p = 0.41) and in 24 patients in the validation cohort . List and Design learning was used for memory assessment.Verbal and visual memory was assessed preoperatively and 1 year postoperatively using the Adult Memory and Information Processing Battery (AMIPB).z scores. Significant memory decline was defined as decline below the 90% reliable change index (RCI) as described previously.Change in neuropsychological performance 1 year after epilepsy surgery was measured as the difference in pre‐ and postsurgical memory MRI data for the development cohort were collected between September 2005 and August 2012 on a 3T Signa HDx Scanner  at the Epilepsy Society. A coronal T1‐weighted 3‐dimensional (3D) fast spoiled gradient echo with repetition time (TR)/echo time (TE)/inversion time (TI) = 6.6/2.8/450 milliseconds, matrix = 256 × 256 × 178, field of view (FOV) = 24 × 240 × 196mm, voxel size = 0.9375 × 0.9375 × 1.1mm was acquired in all subjects.In the validation cohort, subjects underwent imaging on a 3T GE Discovery MR750. A 3D T1‐weighted inversion‐recovery fast spoiled gradient recalled echo  was acquired in all validation subjects.http://niftyweb.cs.ucl.ac.uk/program.php?p=HIPPOSEG) to automatically extract the initial hippocampal masks.First, we used HipposegTo assess intrarater variability of this combined manual‐automated approach, one blinded rater manually corrected Hipposeg segmentation in randomly selected 10 TLE patients on two different occasions 3 months apart and compared the resulting masks using Dice coefficients.Hippocampal volumes were corrected for total intracranial volume (TIV) as described previously.3D surface meshes were extracted from binary hippocampal segmentations and parameterized with a spherical harmonics point distribution model (SPHARM‐PDM).To enhance the interpretation of hippocampal surface maps, several groups have defined heuristic boundaries between hippocampal subregions.http://www.math.mcgill.ca/keith/surfstat/). Two independent variables  were analyzed in 3 groups .We statistically compared pointwise displacement values on hippocampal surfaces using fixed‐effect linear models implemented in SurfStat . The outcome parameter used was the change in p < 0.05.We report findings corrected for multiple comparisons using random field theory for nonisotropic images on a cluster level,The effect size is shown on T‐value maps. A higher T value (blue color) signifies a positive correlation, that is, the association between a regional inward deformation (atrophy) and lower memory performance. A negative T value represents a negative correlation, that is, the association of outward deformations (hypertrophy) with lower memory performance.We also aimed to determine the prognostic value of the significant shape patterns. On an individual level, we determined the predictive value of deformations in these clusters using the area under the receiver operating characteristics curve (AUC). On a group level, we divided patients into those with or without significant inward deviations . We compared poor presurgical performance and the risk of poor postsurgical memory performance between these imaging‐based patient subgroups using logistic regression and provide bootstrapped confidence intervals (CIs) to improve generalizability. In addition, we used logistic regression and calculated the AUC to determine the association of hippocampal shape patterns with memory performance in the validation cohort.t test for independent samples. We correlated hippocampal volumes with neuropsychological scores using the Pearson correlation coefficientDemographic data and volumetric findings are reported as n (%) or mean ± standard deviation. We compared hippocampal volumes between groups with the t = −1,337, p = 0.183) or sex . Detailed participant characteristics are displayed in Table We included 76 patients with LTLE , 69 patients with RTLE , and 39 controls . There were no between‐group differences in age  and visual  memory scores than healthy controls  and visual  delayed recall scores than healthy controls , but RTLE patients had lower visual memory scores than LTLE patients .Both RTLE and LTLE patients had lower verbal . There were no significant changes in visual memory after left or right ATLR.Postsurgical (1 year) verbal memory decline was more common after left compared to right temporal lobe removal  and RTLE (t = −6.467) patients compared to controls .The ipsilateral hippocampus was significantly smaller in both LTLE  and greater right hippocampal volume with better visual memory  before surgery .For all TLE patients, a greater left hippocampal volume weakly correlated with better verbal memory . Although significant, these correlation coefficients (r < 0.30) only suggest a weak linear relationship between overall hippocampal volume and neuropsychological performance.The presurgical volume of the left hippocampus predicted postsurgical change in verbal memory for all patients with TLE . Atrophy here was a significant predictor of poor verbal memory , and this association remained significant when controlling for presence of HS (p = 0.009). This pattern was, however, not predictive of poor visual memory performance .Patients with (n = 55) compared to those without (n = 90) significant atrophy in the left superolateral hippocampal head see Fig A had a 2p = 0.003).In the validation cohort, patients with (n = 13) compared to those without (n = 42) significant atrophy in the left superolateral hippocampal head had a 3.3‐fold  higher risk of poor verbal memory with an AUC of 0.74 (p < 0.001). The magnitude of this atrophy was an individual predictor of poor visual memory , and it remained significant after controlling for HS (p = 0.002). This pattern was not predictive of poor verbal memory .Patients with (n = 33) as opposed to those without n = 112) significant atrophy of the bilateral inferomedial hippocampal surface . This pattern was predictive at an individual level  but was not significant when controlling for HS . There were no shape abnormalities predictive of visual memory decline.Eighteen of the 55 patients who underwent left ATLR had an atrophic left hippocampal tail see Fig A. This pp = 0.04).In the validation cohort, patients with (n = 3) compared to those without (n = 21) significant atrophy of the left hippocampal tail had a 2.1‐fold  higher risk of postsurgical verbal memory decline with an AUC of 0.74 . Thus, hippocampal shape patterns predictive of poor visual memory need to be interpreted with caution, and validation in a larger cohort is warranted. Our analysis was restricted to the hippocampal surface, and hippocampal subfields hidden in depth (CA4) could not be explored. We provided heuristic subfield boundaries on our hippocampal figures, but these approximations need to be interpreted with caution. A limitation inherent to all studies in refractory TLE patients undergoing epilepsy surgery is that patients are treated with antiepileptic drugs and the influence of medication on cognition cannot be eliminated.Not all morphological results found in the combined epilepsy group translated to the LTLE and RTLE subgroups. Some of these differences can be attributed to a reduced power to detect significant results in a smaller group of subjects. Several effects and trends seen on T‐value maps in these subgroups implicate regions similar to those found in the overall patient group. Similar trends compared to the overall group were observed in relation to verbal and visual memory in LTLE see Fig C, D and Hippocampal surface‐shape analysis can demonstrate hippocampal morphology and its impact on cognitive function, which is not captured by global volume measurements. Our results suggest a subregionally specific representation of memory functions in the hippocampus, which will be relevant in view of recently developed highly selective surgical procedures .T.S.P., S.B., P.J.T., M.K.S., S.B.V., M.T., J.S.D., M.J.K., and M.G. contributed to the conception and design of the study; T.S.P., C.C.‐L., I.C., J.d.T., J.L.B., L.C., G.P.W., S.B.V., J.S.D., M.J.K., and M.G. contributed to the acquisition and analysis of data; T.S.P., C.C., I.C.‐L., M.J.K., and M.G. contributed to drafting the text and preparing the figures.Nothing to report.TABLE S1. Review of Quantitative Histology Studies Analyzing the Association of Hippocampal Subfield Neuronal Counts and Verbal/Visual MemoryTABLE S2. Association of Pathology with Presurgical Memory PerformanceTABLE S3. Association of Atypical Language Lateralization with Pre‐ and Postsurgical Memory Scores in LTLEClick here for additional data file.


In this work, we present a procedure for synthesizing [16]andS4 in 45% yield , together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester , an ether-linked isothiocyanate  and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions.The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS While oneS4-ol) . This coribution ,30. To hhelators B, bottom4 was initially reported by Meadow and Reid in 1934, who identified the difficulty of the formation of rings containing more than 12 members  [4-diol and [16]aneS4-ol, was disclosed later, using a multistep approach to prepare the asymmetric analogues of [16]aneS4 [The synthesis of [16]aneSditions) . As ment16]aneS4 ,29. This16]aneS4 . While t4-ol 7, using a method adapted from Lyczko and Li aneS4-ol 7 .On this backdrop, several different strategies were considered, accounting for synthetic practicality and compound stability. To broaden the application of the new macrocyclic chelator derivatives, three different linker types were prepared B, bottomo and Li ,29, and o and Li ,32. Stareld 76%, . Transfo4-ol 7 in hand, we began the construction of the functional conjugation sites . Ester-linked chelators could have a potentially faster catabolism in vivo, which has been recognized as enabling a faster radionuclide clearance, which is potentially desirable for long-lived therapeutic radionuclides aneS4-ol 7 was decorated with N-Boc-3-aminopropyl methane sulfonate to give the N-protected intermediate 11 (78% yield). This compound was then deprotected under acidic conditions and transformed into the corresponding isothiocyanate via consecutive reaction of the amine with N,N′-thiocarbonyldiimidazole under alkaline conditions (see SM for more details). Via this route, isothiocyanate 13 was obtained in a relative straightforward fashion . Notably, the amino intermediate 12 was also transformed directly into the corresponding azido compound 23 using a diazo transfer reagent (75% yield). Azides are extremely useful due to their practical bioconjugation via azide–alkyne cycloadditions under various conditions in vitro and in vivo [With macrocycle [16]aneSon sites . Previouy Lyczko . In ordenuclides . The car in vivo .4-isothiocyanate 13 proved to be sufficient to be a versatile synthetic framework for alternative strategies. While the overall yield of [16]aneS4-ol 7 could be improved further by using the suggestions from Meadow, Reid and Ochrymowycz (vide infra) aneS4-ol 7, directly into the corresponding [16]aneS4-isothiocyanate 13 (4-ol 7 with 3-bromo propaneisothiocyanate or 4-(bromomethyl) phenyl-isothiocyanate, resulted in only trace amounts of desired products.The route towards [16]aneSe infra) ,32, we qvailable , and com2CO3 in DMF for several days at 45 °C. This gave 1,11-diiodo-4,8-dithiaundecane 6 in good yield . At this point we wanted to evaluate whether we could use dihydrolipoic acid (DHLA) as the 1,3-dithio coupling partner in the final macrocyclization. DHLA can be prepared quantitatively from α-lipoic acid under mild reducing conditions; NaBH4, NaHCO3 in H2O (see SI for details) aneS4-ol 7, macrocyclization with DHLA to form 22 appears to be an attractive gateway to functionalizable derivatives. Further attempts to improve the yield of this step were unsuccessful, and it was observed that 1,11-diiodo-4,8-dithiaundecane 6 was unstable and could not be stored for several days, even under inert atmosphere (argon) at −20 °C (see SM for more details and discussion). Based on these observations, we hypothesized that 6 rapidly decomposes due to the presence of iodide, via a reversed sulfonylation degradation pathway or via polymerization. The instability of these compounds was also attributed to external factors such as light and heat, including the presence of heavy halogens (such as iodine), which was also observed by Meadow and Reid aneS4-NCS 13, [16]aneS4-N323, we elected 9 and 13, to be conjugated to octreotide, as a proof-of-concept for further conjugation studies. Octreotide is a mimic of natural somatostatin, which is a growth hormone-inhibiting hormone, which regulates the endocrine system, affecting neurotransmission and cell proliferation aneS4-NHS and the [16]aneS4-NCS were successfully conjugated to octreotide, a mimic of natural somatostatin, as an initial proof-of-concept for further bio-conjugation studies.In conclusion, a number of novel bifunctional chelators were synthetically prepared for application in soft radiometal theranostics. The chelator, a [16]aneS


Intimate partner violence (IPV) during pregnancy has negative health impacts on the woman and the fetus. There is a lack of evidence supporting effective interventions to prevent IPV during pregnancy. This user-involvement study was conducted to get feedback on a culturally sensitive, tablet intervention containing questions about violence and safety-behaviors and a video promoting safety behaviors. This resulted in important feedback on the intervention content. Our findings show that women are in favor of disclosing IPV via a tablet. They suggested ways to address barriers for disclosure, such as safeguarding anonymity and creating a trustful relationship with the midwife. Intimate partner violence is considered a serious social and public health problem, with one in three women having experienced physical and/or sexual violence by an intimate partner some time during their life . PregnanA recent meta-analysis of IPV during pregnancy, which included 92 studies from 23 countries, reported that the prevalence of physical, sexual, and emotional abuse was 13.8%, 8.0%, and 28.4%, respectively . In NorwViolence during pregnancy is associated with adverse complications, such as premature contractions, miscarriage, premature birth, still birth, and low birth weight . In addiAntenatal care is considered a “window of opportunity” to address IPV because women are in regular contact with health professionals throughout the pregnancy . PregnanRecommended interventions for IPV in primary care settings involve questions about violence, safety-planning strategies, and help-seeking strategies . The eviScreening for IPV in antenatal care might increase identification of violence . NorwegiMobile health technology  such as mobile phones, tablets, and other wireless computing devices have the potential to overcome some of the barriers regarding face-to-face interventions . The tecThe Safe Pregnancy study is a randomized controlled trial (RCT) to test the effectiveness of a tablet-based, culturally adapted intervention in antenatal care aiming to promote safety behaviors and prevent IPV among pregnant Norwegian, Pakistani, and Somali women . The RCTA modified version of the Abuse Assessment Screen (AAS), a five-item screening tool for violence in pregnancy, is part of the baseline questionnaire . Women wThe intervention video lasts for 7 min and consists of storytelling combined with digital content, including pictures, images, sound, and video, focusing on information about the definition and types of IPV, the cycle of abuse, IPV during pregnancy and the health consequences, help-seeking strategies, and safety-promoting behaviors. According to The Safe Pregnancy study is a culturally sensitive intervention aiming to promote safety behaviors during pregnancy. The intervention materials have been professionally translated into Norwegian, English, Urdu, and Somali. With help from the current user-involvement study (UIS), the intervention has been culturally adapted by involving women with Norwegian, Pakistani, and Somali backgrounds in the development process.The UIS presented in this article was an iterative development process that engaged users in conceptualization, design, and final production of the tablet-based intervention . User inThe recruitment of participants took place over 9 months in south eastern Norway starting in May 2017. Participant inclusion criteria for individual interviews were largely identical to those in the Safe Pregnancy study to facilitate similarities in the two study populations . Norwegin = 3), India (n = 1), and Iran (n = 1), were skilled professionals reporting high education levels, and were community workers, social workers, and teachers.Sixteen women were recruited for individual interviews. The women’s ages ranged from 22-47 years. The study had a qualitative, explorative design to gain a deeper insight into perceptions about a culturally sensitive intervention. Individual and focus group interviews were conducted by the first author, either at the woman’s home, shelter, or in a private room at the university. The interviews followed a semi-structured guide and the main themes were as follows: (a) perceptions of the questions about violence and safety behaviors; (b) perceptions of what information a video about violence and safety behaviors should contain; and (c) perceptions of the draft video. Two pilot interviews were conducted to test the effectiveness of the interview guide and minor changes  were undertaken. The two interviews are included in the data. All of the interviews lasted between 45 and 90 min, were audiotaped and transcribed verbatim.The analysis of the interviews was guided by a thematic analysis strategy . In searThe Regional Committee for Medical and Health Research Ethics (REC) approved the study (ref.nr: 2017/358) and the interviews followed the Helsinki Protocol  and ethiperceptions of questions about IPV and safety behaviors illustrates whether participants perceive the questions as relevant and easy to understand linguistically. However, the questions are sensitive and may prevent disclosure of IPV. Facilitators and barriers to disclose IPV via a tablet elucidated several aspects that participants thought were important for women to feel safe when disclosing violence. The importance of anonymity emerged as an essential prerequisite for disclosing violence. From the analysis of the participants’ perceptions of a video about violence and safety behaviors two main themes emerged. One, perceptions of the information in the video about IPV and safety behaviors, describes the importance of focusing on information about different forms of violence, safety-promoting behaviors, and help-seeking strategies. Second, perceptions of the tools used in the video about IPV and safety behaviors illuminates the desire for the tools to be perceived as stress reducing, helpful, and promoting the safety behaviors to be remembered.. . . that you start with the mild and then it may be easier to be brave to answer honestly . . . maybe I would start with milder forms of violence like “followed me, harassed me, told me I was crazy, stupid, or not good enough.” (Participant 5)The first theme illustrates how women perceived the questions about IPV and safety behaviors. All participants said that the questions about violence and safety behaviors were easy to understand; however, they perceived the questions to be sensitive. A Norwegian woman suggested changing the order of the questions about violence. She emphasized that all of the questions are sensitive but that it might be easier for study participants to disclose IPV if the first questions address milder forms of violence:A lot of this has happened to me. . . . I received help at a crisis shelter because I called the police. I had a code on my phone . . . with the neighbor. (Participant 3)Although the women identified the questions as sensitive, they said that the questions were relevant. Independent of their ethnic backgrounds, women revealed experiences with the acts of violence and the use of safety behaviors mentioned in the questionnaire:Based on participants’ feedback, we changed the order of the questions about violence, addressing milder forms of violence first. The women pointed out that the new order of the questions about violence was appropriate and that it could possibly facilitate disclosure of IPV.. . . it (the answers) has to be anonymous . . . if you answer and know that the people at the health center can find out . . . but if your husband cannot see the answers, you may give honest answers. (Participant 2)The women were asked what would encourage them to disclose experiences with IPV via a tablet. The importance of anonymity was the most common subtheme in this theme. Independent of ethnicity and former experiences of IPV, women highlighted information about anonymity as a prerequisite for disclosure. A common statement from the women was:. . . it is difficult to answer . . . the questions are sensitive. Therefore it is important that you give information about anonymity at the start . . . and again before the questions about violence and safety behaviors. (Participant 10)Some of the women emphasized the importance of repeating information about anonymity in the different sections of the questionnaire. A Somalian woman stated the following:. . . is it anonymous? Why does she (the midwife) ask me? Does she (the midwife) know something? (Participant 15)Despite information about anonymity, women with an immigrant background particularly expressed doubts regarding the trustworthiness of the information about anonymity. A woman originating from Pakistan expressed her skepticism in the following:. . . the questions about violence and safety behaviors cannot be answered honestly. She must know that she is anonymous to answer honestly and you must create trust first through the midwife. (Participant 6)For women with an immigrant background, the assurance that their answers will be handled confidentially did not seem to be enough to disclose experiences of violence. In addition to written information about anonymity in the questionnaire, the women stated that oral information about anonymity from a midwife they trust might facilitate disclosure:. . . yes, definitely, because you are not writing your name, you are not scared. You can say: “No, I’m not that person who answered this.” (Participant 16)Despite the common skepticism regarding trust in anonymity, another woman from Pakistan outlined that the use of the tablet could promote this trust:. . . then (living in a violent relationship), I would not have dared to answer the questions about violence honestly. If you feel that it does not have any consequences, you might answer honestly and it would be liberating and helpful. (Participant 2)While all women suggested important facilitators for IPV disclosure, they also highlighted potential barriers. All the women in our study emphasized that it would be easier to answer questions about violence and safety behaviors honestly, if their disclosure would not lead to serious consequences. A Norwegian woman with a history of IPV stated:. . . and it is this talk about honor: “what would people say about me?,” “what would people think about what I say?” and “what would happen to my children?” (Participant 15)Independent of ethnicity, a common fear was that a violent partner would get to know about their disclosure and that it would expose the women and their children to further harm. In addition, some women expressed fear of shame as a barrier for revealing a violent relationship. Women with an immigrant background described a more complex situation addressing culturally sensitive aspects:The Somalian women expressed the difficulties for women from their culture to disclose violence as they fear that Child Welfare Services would take their children away from them.. . . if you ask someone while sitting in front of them, then she will definitely not (answer) but alone, she can (answer). (Participant 16)All of the participants stated that being in a room alone while answering the questions could promote disclosure of violence. A common statement described by a woman originating from Pakistan was:However, the participants expressed that the questions about IPV and safety behaviors could cause emotional distress. Most participants said that the information about encouraging women to speak with their midwife if they have any concerns after filling out the questionnaire was important to promote safety.Due to participant feedback, information about anonymity was given at the start of the questionnaire and repeated before the questions about IPV and safety behaviors. In accordance with the Safe Pregnancy study guidelines, women were alone while filling out the questionnaire.. . . it should not solely be about those who need to go to the emergency room. It should include psychological violence as well. (Participant 5)Before seeing the draft video, participants provided varying advice on what information a video about safety behaviors should contain. Irrespective of ethnicity and experiences of violence, all participants emphasized that the video should contain information about different forms of violence. A common statement expressed by a woman originating from Norway was:. . . it’s important that the girls know what violence is and that they do not feel that they are alone in being controlled, isolated, being the slave for the in-laws and being exposed to physical and psychological violence. (Participant 6)Most women from immigrant backgrounds said that violence is accepted in their culture and that different forms of psychological violence are interpreted as normal behavior. They highlighted the importance of informing participants about what violence is, that violence is illegal in Norway, and that women suffering violence are victims. A Pakistani woman with a history of IPV said:. . . I don’t pay attention, because this does not apply to me. It is this to be partly isolated, partly deprived of the opportunity to spend your money and such. . . . Such things had been helpful to shed light on. (Participant 2)After seeing the draft video, the women said that the information about physical violence was relevant and good. However, women with a history of psychological violence stated that the information was inadequate and failed to address women who only experienced psychological abuse:. . . why would I need a passport? I’m not going anywhere. So you can think that this is not about you, but somebody else. (Participant 5)Another woman originating from Norway shared this opinion. In addition, she pointed out the challenge of providing culturally sensitive information about safety behaviors that all women suffering violence can relate to:. . . I wanted to know a little more about what could happen to the child when living in a violent relationship. You hope that when the child comes then it will be better and that the family is gathered and . . . that is what makes it so difficult to leave the partner . . . but you also want to put the children first . . . it might be easier to ask for help then. (Participant 3)Some women expressed that they missed information regarding how living in a violent environment could potentially affect their children. A woman explained that information facilitating awareness about the abnormality of violence could make it easier for women to disclose violence and ask for help:. . . I think that the most important safety behavior would be that you dared to talk to someone. Few women will be able to get out (leave the violent partner) alone without help. (Participant 5)The participants highlighted information about what women exposed to violence can do to promote their safety. They presented a variety of suggestions, such as getting hold of their passport, hiding money, and making plans if they have to leave. Most women, independent of ethnicity and experiences of violence, stated that the most important safety behavior would be to talk to someone they trust. A woman originating from Norway outlined why:They need information about where to get help. If you were born and raised here, you know your rights. But is it one who comes from abroad and is completely unknown, has no family, no chance to get out, it is very difficult. (Participant 7)The participants outlined the importance for women living in a violent relationship to receive information about where to get help. They expressed common suggestions such as having websites and phone numbers for the police and shelters. Women with immigrant backgrounds described a more complex situation:Resulting from participants’ feedback, the video was expanded to include more information about psychological abuse and potential consequences for children living in a violent environment.The voice (the narrator) was clear and to the point. She (the narrator) spoke calmly and the music was comfortable, as comfortable as possible in relation to that message (sensitive) . . . I think it was nice that there was music . . . it reduces the . . .  . . . it (the music) makes the information about a sensitive topic less sensitive. (Participant 11)This theme concerns how women perceived the tools used in the video. All women emphasized that the sound, including the background music and the narrator’s voice, was perceived as calming, thus reducing emotional distress. A Norwegian woman expressed this common experience as follows:. . . the soothing music in the background, it makes you think and consider (about the violent situation). (Participant 15)The clear, calm voice and soft music made it easy to concentrate and receive the message. A Pakistani woman elaborated on this feedback:. . . I like that you use pictures with different people . . . not everyone looks the same. Everyone is not Norwegian, blonde with blue eyes. I can see myself, a woman with a scarf on her head holding money in her hand. I think: “she is smart” and I can do the same (hide some money). (Participant 8)The majority of the participants experienced the pictures in the video as informative and easy to understand and relate to. They highlighted that the pictures illustrated different forms of violence and the safety behaviors were perceived as relevant and helpful. In addition, the participants emphasized that the pictures about safety behaviors illustrated by women with different ethnic backgrounds might facilitate identification across cultural differences. A Somalian woman gave important feedback on this aspect:. . . I did not quite understand the picture illustrating psychological violence. I think that it does not belong here. I think about how I can illustrate it, and it is not easy to say. It is difficult to find images of psychological violence and hence understand what psychological violence is. (Participant 3)Although most of the pictures were informative and easy to understand, the pictures illustrating psychological violence were perceived as confusing. A Norwegian woman with a history of IPV explained the challenge of illustrating psychological violence:. . . I think it is easier to pay attention when you see pictures . . . that there are no real people, because then it might be easier to relate it (the information) to themselves. . . . I think that it (pictures) might give more room for reflection and thoughts . . . and that it does not go too fast, because they (abused women) can get very occupied in their own experiences and then you will not pay attention to what is happening. (Participant 11)Some women with different ethnic backgrounds, including professional participants from one focus group, suggested using a film with actors instead of static pictures in the video. Despite divergent opinions, most women stated that pictures, to a larger extent than film, can help abused women to identify with the sensitive information in the video. They stated that pictures promoted a quiet atmosphere that reduced emotional distress, and as a result, abused women would be more likely to remember the information in the video. A woman of Norwegian origin communicated common experiences related to the advantage of using a digital narrative with pictures instead of film:Due to the sensitive topic, the women acknowledged that study participants experiencing IPV might suffer emotional distress when watching the video. Hence, they said that it was important to repeat information about safety behaviors at the end of the video.. . . the narrator repeated several times the safety behaviors, and I believe that it is important. The video may cause many thoughts and then you may not hear what is said the first time. (Participant 11)Based on the findings from this study, a short film illustrating psychological violence was included in the video. All other pictures and illustrations were kept. The focus group participants said that the adjusted film illustrated psychological violence well.This study provided important insights to develop a culturally sensitive intervention to promote the prevention of IPV. Our findings show that women are in favor of disclosing IPV via a tablet. They expressed various suggestions about how to address barriers for disclosure, such as safeguarding anonymity and creating a trustful relationship with the midwife.Women in this study were positive about answering questions on violence via a tablet at a MCHC. This is in line with results from prior studies documenting that use of electronic devices may eliminate many of the barriers associated with face-to-face screening . In a stHowever, the majority of women in our study with immigrant backgrounds said that they did not trust the tablet to safeguard their anonymity. Similar to Chang et al. (2012), they were uncertain who would be getting the information from their IPV disclosure on the tablet. This is in line with a qualitative study of Somali-born refugees in Sweden which revealed that questions about violence were met with hesitance . A key fPrevious research has revealed that women do not always disclose experiences of IPV and the prevalence may be underreported . DespiteWomen in our study believed that the safety-promoting video might prevent IPV. However, they asked for more information about psychological violence. Similar to findings in a study by Qualitative and quantitative studies among abused women from different ethnicities have found that concerns for their children can be an important incentive to seeking help . Women iEmotional reactions regarding the sensitive content of the tools used in the video seemed to be unavoidable. Women in our study acknowledged that the video would potentially trigger painful memories, and they expressed important views on the different tools aiming to minimize their emotional impact and ensure abused women’s well-being. Similar to the findings in a qualitative study aiming to modify an internet-based safety decision aid to a New Zealand context , we faciOur study has limitations. Due to a qualitative study design aiming to gain a deeper understanding about a phenomenon, the study sample is too small to draw conclusions about a broader population of women . However


BackgroundTotal knee replacement (TKR) is an artificial joint surgical procedure that replaces the damaged articular surfaces of the knee joint. Despite several studies on the efficacy of intra-articular and intravenous Tranexamic acid (TX) use in reducing blood loss following TKR, the route of TXA administration is still an ongoing topic of debate. Our study aimed to compare total knee replacement efficacy  of intra-articular and intravenous tranexamic acid administration.Material and Methods A Prospective study was conducted at the Department of Orthopedics, Shifa International Hospital, Islamabad. The study duration was six months (August 2020 to February 2021). A sample size of 60 patients was calculated using the WHO calculator. Patients were selected through non-probability consecutive sampling. Patients were randomly divided into two groups; Group A was given intraarticular TXA, while group B was given intra-venous TXA following total knee replacement. Patients were followed for 48 hours. Data were analyzed using SPSS version 24. An Independent T-test was applied, and a P value≤0.05 was considered significant.ResultsA total of 60 patients were included in the study. There were 20 (33.3%) male and female 40 (66.7%). The mean age of patients was 64.4±10.8SD. Post-operative hemoglobin level in group A was 11.09±0.39SD, and in group B was 9.93±1.73SD (p=0.03). Postoperatively, the mean HCT level in group A was 30.53±4.26SD and group B 26.88±5.48SD (p=0.01).ConclusionIntra-articular administration of TXA is more effective than intravenous administration in controlling postoperative blood loss following total knee replacement. Total knee replacement (TKR) is an artificial joint surgical procedure that replaces the damaged knee joint . The priKnee replacement prostheses are divided into three major types . Non constrained prosthesis is associated with providing stability to the prosthesis with patients' muscles and ligaments. Semi-constrained is associated with providing stability to the knee without relying on the muscles and ligaments of the patient. At the same time, a constrained prosthesis is used in patients in whom muscles and ligaments cannot provide any stability . TKR canTranexamic acid (TXA) is a synthetic anti-fibrinolytic agent associated with inhibiting the activation of plasminogen to plasmin. TXA at high concentration can also directly inhibit plasmin activity. The process decreases proteolytic action on fibrinogen and fibrin monomers, ultimately preventing clot stabilization. The use of TXA intravenously in TKR is a common practice. Literature reported the use of TKR in the following forms: 1. A pre-operative dose before tourniquet inflation; 2. An intra-operative dose before deflation of the tourniquet; 3. Post-operative dose 3 hours after surgery; 4. Various permutations combining these three dosesIntravenous use of TXA is associated with a wide distribution of the drug in intra and extracellular compartments . Intra-aWe found limited literature on the comparison of intra articular and intravenous use of TXA in TKR in Pakistan. The literature available on this topic is not enough to reach any conclusion in the settings of Pakistan. This study was done to cover knowledge gaps regarding the efficacy of tranexamic acid administration routes. So, the present study aims to compare efficacy  of intra-articular and intravenous tranexamic acid administration in total knee replacement.A prospective study was conducted at the Department of Orthopedics, Shifa International Hospital, Islamabad. A sample size of 56 was calculated (rounded off to 60), 30 patients in each group using a WHO calculator with µ1=254, µ2=210, SD=60, 95% confidence level, 5% significance level, and 80% power of study [Data analysisData analysis was done with SPSS version 24. Descriptive statistics include the presentation of mean±standard deviation, frequency, and percentages. Inferential statistics will include an independent t-test, and P-value ≤0.05 was considered as a statistically significant finding.A total of 60 patients were included in the study. There were 20 33.3%) male and female 40(66.7%) patients. The mean age of patients was 64.4±10.8SD. There were 10(16.7%) patients in the age group 40-50 years and 50(83.3%) in the age group >50 years. There were two interventional groups; group A 30 (5-%), and group B, 30(50%) patients. Pre-operative hemoglobin level in group A was 12.62±1.14SD and in Group B 12.53±1.41SD (p= 0.780). The post-operative hemoglobin level in group A was 11.09±0.39SD, and group B was 9.93±1.73SD (p=0.03), as shown in table 3.3% maleTotal knee replacement is a cost-effective treatment modality for advanced degenerative arthritis of the knee . The majIn our study, the intra-articular route showed less blood loss in hemoglobin and hematocrit levels and less hospital stay (p<0.05) than intravenous administration of TXA. Huang et al. reported that intra articular and intravenous routes effectively reduce blood loss after TKR . HoweverSome studies also supported the postulation that TXA showed a more effective therapeutic effect after proteolysis of plasmin dissolved prematurely fibrin clot. TXA showed a more effective response at the active bleeding site of the wound than within blood vessels . MoreoveOur study did not find any significant difference in complications in both groups. However, Wang et al. promptly reported that the intravenous route is associated with more complications, including surgical site infection and bleeding . Moskal Strength: To the best of our knowledge, it is a unique study in our local setup. It is challenging to conduct these studies as very few centers perform TKR in such numbers.Limitation: Small sample size and conduction of study at a single center limits generalization of results.Intraarticular administration of TXA is more effective than intravenous administration in controlling postoperative blood loss following total knee replacement. Our study did not find any significant difference in complication after intra-articular and intravenous administration of TXA. More detailed, multicenter clinical trials are required to understand the efficacy and cost of treatment in-depth.


Apart from the gelation rate, the use ofCu2+ led to the rapid realization of gel characteristics.The results here provide strategies for process engineering, ultimatelyto determine the phase-transition rates. In addition, a microfluidicswitch was successfully operated based on a better understanding ofthe reversible crosslinking of the chitosan hydrogel. Rapid gelationwas required to close the channel, and a quick switchover was achievedby a dissolution enhancement strategy. As a result, factors that regulatedthe rates of gelation or dissolution were found to be useful to operatethe fluidic switch.The importanceof chitosan has been strongly emphasized in literature because thisnatural polymer could not only remove heavy metal ions in water butalso have the potential for recyclability. However, reversible phasetransition and its dynamics, which are highlighting areas of a recycleprocess, have not been studied sufficiently. Here, we present dynamicstudies of the dissolution as well as the gelation of a physicallycrosslinked chitosan hydrogel. Specifically, a one-dimensional gelgrowth system and an acetate buffer solution were prepared for theprecise analysis of the dominant factors affecting a phase transition.The dissolution rate was found to be regulated by three major factorsof the pH level, Cu This indicates that chitosan is certainlyattractive because this natural polymer could reduce the environmentalconcern as well.Chitosan is a polysaccharideobtained fromthe deacetylation of chitin.16 This is mainlydue to water solubility changes determined by the pH level. In detail,chitosan polymers become soluble, accompanying the protonation ofNH2 below pH 6.3 and start to form a gel due to the deprotonationof NH3+ above pH 6.3.17 Similarly, coordination bonds between chitosan andtransition-metal ions are also related to the pH levels of the solutions.For example, the chitosan/Cu2+ hydrogel was obtained abovepH 6.3, while the chitosan polymer was soluble in aqueous solutionsat the pH level below 6.3  was also investigatedcompared to Cu2+. At the end of the study, a microfluidicswitch was operated based on the reversible crosslinking of the chitosan/Cu2+ hydrogel.Here, we have conducted dynamic studies ofthe dissolution as well as the gelation of physically crosslinkedchitosan/metal-ion complexes. Among metal ions, Cu22.12+ hydrogel formation rate was analyzed through a one-dimensionalgelation system. A glass mold filled with the chitosan/Cu2+ solution and a clotting bath in which NaOH was dissolved were bothprepared. The chitosan/Cu2+ solution started to form agel as soon as the glass mold was immersed in the clotting bath. Asdescribed in 2+ hydrogel was finallyobtained. Then, a one-dimensional grown part was verified using therheological characterization. The values of the storage modulus werealways higher than those of the loss modulus regardless of Cu2+, which indicated that the hydrogel was successfully fabricated. Besides, the gelation processwas visual because Cu2+ dissolved in the chitosan polymersolution took part in the gelation through coordination bonding betweenNH2 and Cu2+ considering the color change fromlight blue (chitosan/Cu2+ solution) to deep blue (chitosan/Cu2+ hydrogel). The origin of different colors is that NH2 caused more splitting of the d-orbital of Cu2+ than water (H2O), as the N atoms in NH2 weremore electropositive than the O atoms in H2O. As a result,the chitosan/Cu2+ hydrogel absorbed higher energy correspondingto yellow light, the complementary color of deep blue.29Asshownin 3+ is deprotonated toNH2 on aqueous surfaces under alkaline conditions. Therefore,the rate of deprotonation from NH3+ to NH2 should be a major factor affecting the chitosan hydrogelformation outcome. As shown in – through the grown hydrogel layer in order to deprotonate NH3+ at the sol/gel interface. The 2 wt % NaOH aqueoussolution required more than 72 h until gelation was fully completeowing to the low diffusion rate of OH–. Apparently,the chitosan gel growth rate strongly depended on the concentrationof NaOH. From a similar point of view, we predicted that a small amountof acetic acid in chitosan solution could also be supportive in orderto promote the gel growth. According to the previous work reportedby Dobashi et al., a large amount of acetic acid in the chitosan solutioninterrupted the chitosan gel growth due to a delay in the deprotonationof NH3+ at the sol/gel interface.20For the chitosan polymers, they are able to become a physicallycrosslinked gel when NH2+ (Cu2+/NH2 =0.0–0.5) on the gel formation rate with the same concentrationof NaOH was mostly negligible  also grew at a speed identical to that of a pure chitosan hydrogelin the 20 wt % NaOH aqueous solution. Moreover, we investigated thegelation behavior with different metal ions  incorporated withthe chitosan polymer . In brief,the chitosan/metal-ion gel  growthrate was undoubtedly accelerated when the concentration of NaOH becamehigh. For example, the chitosan/Fe3+ hydrogel grew fasterin 10 wt % NaOH aqueous solution compared to 5 wt % NaOH aqueous solution.However, each chitosan/metal-ion hydrogel grew at a different rate,which followed the order of Fe3+ ≈ Cu2+ > Mn2+ ≈ Ca2+. This was probablycaused by the change of affinity of NH2 to metal ions.According the previous report, ethylenediamine favored Fe3+ and Cu2+ rather than Mn2+ and Ca2+.27 This probably resulted in byproductssuch as Mn(OH)2 and Ca(OH)2, which interruptedthe diffusion of OH–. As explained by Nie et al.,Ca(OH)2 precipitation within the chitosan hydrogel wasclearly observed.19 The result indicatedthat the strong affinity of NH2 to Cu2+ encouragedthe growth of the chitosan/Cu2+ hydrogel.On the other hand, the influence of theconcentration of Cugligible 2c,d. Thi2+ complexes  with sequential drops of aqueousNaOH solutions (0–10 wt %) were measured  than the pure chitosan hydrogel(Cu2+/NH2 = 0.0) could be other evidence ofthe strong crosslinking through coordination bonding .Next, theviscosity changes of the chitosan/Cumeasured 3. As shomeasured 3d,e. Eve complex3c tended complex3b when t– was the dominant driving force of thephysical gelation of chitosan/Cu2+ regardless of the concentrationof Cu2+. However, the Cu2+ within the chitosanpolymers accelerated the gaining of gel characteristics.In conclusion, the higher diffusionrate of OH2.22+ hydrogels withvarious compositions (Cu2+/NH2 = 0.0–0.5)were prepared using the 10 wt % NaOH aqueoussolution with the one-dimensional gelation system. That is to say,the hydrogels obtained from the gelation test were applied to thedissolution test as the concept of the recyclable process. Then, factorsthat disintegrate a physically crosslinked chitosan/Cu2+ hydrogel were analyzed using 1.0 M acetate buffer solution systemwith pH levels from 3.8 to 5.6 accompanied by mechanical stirring.30 Besides, the viscositywas measured using a rotary viscometer in order to analyze the dissolutionquantitatively. In detail, 1.0 g of the chitosan hydrogel was immersedin 10 mL of the buffer solution whose initial viscosity was 3.5 ±0.7 mPa s. After that, the viscosity of the solution in which thechitosan polymer disintegrated gradually increased until the hydrogelwas completely dissolved. Then, the viscosity uniformly convergedat 9.4 ± 1.0 mPa s because the final concentration of the chitosanpolymer was equal. Therefore, the convergence of the viscosity withoutany residual chitosan/Cu2+ hydrogel indicated the completedissolution. Here, t90 was consideredas the dissolution time. As shown in t90 was definedas the time to reach 90% of the converging value after Weibull fitting.Even though the heterogeneous regions should exist during dissolution,we reported the viscosity measured in the solution representatively.Before the dissolution test, chitosan/Custirring4a. This 2 to NH3+ should be a majorfactor affecting the chitosan hydrogel dissolution outcome. As shownin 2+ hydrogel due to the acetate buffersolution.2+ hydrogel were discovered.The chitosan/Cu2+ hydrogel dissolved slowly as the concentrationof Cu2+ increased. Moreover, Cu2+ led to a lowermaximum pH level, at which point the chitosan/Cu2+ hydrogelwas completely disintegrated. For example, the chitosan/Cu2+ hydrogel  remained swollenat pH levels ranging from 5.2 to 5.6, where the pure chitosan hydrogelcould be perfectly soluble . For example, 2,2′-bipyridine is insoluble in water andcyanide ions are weakly acidic with a pKa of 9.2. Here, NaNO2 was used as the source of NO2–, and its high solubility in water wasreadily confirmed, more than 50 g/100 mL. As expected, NO2– dissociated from NaNO2 enhanced thedissolution of the chitosan/Cu2+ hydrogel, and it is shownin 2– (NO2–/Cu2+ = 0–90) were utilized at the same pH level.In addition, the maximum pH level at which a fully disintegrated solutionwas obtained tended to be elevated when NO2– was applied. For example, the chitosan/Cu2+ hydrogel(Cu2+/NH2 = 0.2) could be completely dissolvedat pH levels ranging from 5.0 to 5.6 when NO2– was utilized (NO2–/Cu2+ =9–90), while it remained swollen at a pH level above 5.0 withoutNO2– (NO2–/Cu2+ = 0). The strong effect of NO2– was investigated when other metal ions  were utilized instead of Cu2+ (Table S3). For example, it took at most50 min to dissolve the chitosan/Fe3+ hydrogel (Fe3+/NH2 = 0.2) at pH 5 with NO2– (NO2–/Mn2+ = 90), whilethe same hydrogel was completely disintegrated after 450 min at pH5 without NO2–. However, it was especiallynotable that metal ions apparently affected the dissolution rate ofthe chitosan/metal-ion hydrogels, probably due to the different affinityof NH2 to metal ions.27 For example,the chitosan/Ca2+ hydrogel tended to be dissolved fasterthan others, and this was probably because of the weak affinity ofNH2 to Ca2+ caused by the absence of the d-orbital.19Next, two additional key factors which regulate thedissolution rate of the chitosan/Cu soluble 5a. This 2– did not work when the pure chitosanhydrogel was dissolved (Cu2+/NH2 = 0.0). Forexample, a converging time at pH 5 was not significantly affectedby NO2– , as shown in 2– (NO2–/Cu2+ = 9) shortens the converging time of the viscosity whenchitosan/Cu2+ was dissolved  aqueous solution was greenish,whereas the Cu2+/NH2 (ethylenediamine) aqueoussolution was bluish. However, the dissolution of the chitosan/Cu2+ hydrogel was not expected at a pH level above 6.3, evenwith NO2–, mainly because chitosan polymerscould not become hydrated unless protonation occurred.Interestingly,NOissolved 4c,d. Fig2+ hydrogel was intended to be dissolved at a pH below 5.6.Cu2+, which contributed to stronger crosslinking, led toa slower dissolution, while NO2–, whichtended to attract Cu2+, accelerated the dissolution processdramatically. Particularly, NO2– couldhelp the chitosan/Cu2+ hydrogel dissolve faster comparedto the pure chitosan hydrogel.In conclusion,two other factors can clearly be involved when the chitosan/Cu2.32+ hydrogel. Figure S5 shows the simple construction of thefluidic switch system which was operated via the reversible crosslinkingof chitosan/Cu2+ complexes.A fluidicswitch for water flow regulation was operated by means of the reversiblecrosslinking of the chitosan/Cu2+ solution (Cu2+/NH2 = 0.2) and a 10 wt % NaOH aqueous solution were injected simultaneouslyat a rate of 20 mL/min from opposite directions perpendicular to thewater flow line. A blue gel then successfully formed despite the continualsupply of water  started to flow alongthe detour route in 5 s .47 The final dimensionsof the channel were set to 300 μm × 50 μm (width× depth), and an initial water flow check was implemented beforethe switch test  started to flow along the detour routein 5 s  apparentlyaffected the dissolution as well as the gelation, a phase transitionof the chitosan/metal-ion hydrogel was similarly controlled by thefactors such as NaOH, pH, and NO2–. Finally,a fluidic switch was operated via the reversible crosslinking of chitosan/Cu2+ hydrogels. The gel which formed at a high concentrationof OH– blocked the water flow perfectly. This gelcould not be removed until an acidic aqueous solution was injected.Furthermore, NO2– dissolved in an acidaqueous solution shortened the operating time from closed to open.Moreover, a switch system could be successfully applied to a microfluidicchannel as well. We expect that a controllable microfluidic devicecould be potentially applied to various fields such as hemostaticsystems and trace metal analysis. Besides, this study provides a betterunderstanding of the reversible crosslinking of the chitosan/metal-ionhydrogel and helps with the preparation of comprehensive strategiesfor the recycle process.In summary,dominant factors which influence the rates of the reversible crosslinkingof chitosan/Cu44.13COOH aqueous solution), and the degree of deacetylationis 75–85%. Acetic acid (CH3COOH), sodium acetate(CH3COONa), sodium hydroxide (NaOH), copper chloride (CuCl2), manganese chloride (MnCl2), iron chloride (FeCl3), calcium chloride (CaCl2), and sodium nitrite(NaNO2) were purchased from Daejung Chemical and MetalsCo., Ltd. and were of analytical reagent grade.Chitosan  was used as a rawhydrogelmaterial. The average viscosity of chitosan is 500 cp . Each solutionwas added to a glass mold before being immersed in a clotting bath.Clotting baths were prepared by dissolving various amounts of NaOHpellets in deionized water, with the final concentrations held inthe range of 2–20 wt %. The growth of the chitosan/Cu2+ hydrogel was started when the chitosan/Cu2+ solutionwas immersed into the NaOH clotting bath. Each of the glass molds(2.5 mL of chitosan/Cu2+ solution) should be immersed inat least 500 mL of the NaOH aqueous solution in order to ensure uniformgelation. The chitosan/Cu2+ hydrogel growth rate was calculatedaccording to the gel thickness, which was measured every hour. Thecolor change from light blue (chitosan/Cu2+ solution) todeep blue (chitosan/Cu2+ hydrogel) was observed when thegelation proceeded.Chitosansolution was prepared by dissolving chitosan powder in 2 vol % ofa CH4.32+ solution  were prepared using the method describedin 2+ solution was added to a glass mold,and a spindle which was connected to a rotary viscometer  was dipped into the solution. The viscosity of the complexwas recorded by adding an aqueous solution of NaOH with a speed of0.3 mL/min.The NaOH aqueous solution (2–10wt %) as well as the chitosan/Cu4.42+ hydrogels were prepared usingthe method described in 2+ hydrogels wererinsed with deionized water repeatedly and stabilized in a deionizedwater bath for 24 h before the dissolution test. 1.0 M acetate buffersolutions with pH levels ranging from 3.8 to 5.6 were prepared inorder to clarify the effect of the pH on the dissolution speed ofthe chitosan/Cu2+ hydrogel. The relative concentrationsof CH3COOH and CH3COONa at each pH level werecalculated with the Henderson–Hasselbalch equation .The prepared buffer solutions were checked with a pH meter . Then, various amounts of NaNO2 powderwere added with different molar ratios between NO2– and Cu2+ (NO2–/Cu2+ = 0–90). The prepared chitosan/Cu2+ hydrogels were immersed in buffer solutions with a stirring speedof 300 rpm at room temperature. Every 1.0 g of the chitosan/Cu2+ hydrogel should be immersed in 10 mL of the buffer solutionunder each condition. In order to confirm the complete disintegrationquantitatively, the viscosity of the environmental buffer solutionwas measured using a rotary viscometer. The viscosity gradually increasedas the chitosan hydrogel disintegrated into the buffer solution. Finally,the complete dissolution was determined when the viscosity becameconstant without any residual chitosan/Cu2+ hydrogel. Here, t90, the time to reach 90% of the convergingvalue after Weibull fitting, was considered as the dissolution time.Chitosan/Cu4.52+ solution and NaOH solution.To close the water line, 0.02 g/mL of the chitosan/Cu2+ solution (Cu2+/NH2 = 0.2) and NaOH  aqueous solutions were simultaneously injected. The injectionrate for both syringes was fixed at 20 mL/min. The water flow ratewas calculated according to the amount of water which flowed in anoperating interval. To reopen the water line, a CH3COOH/NO2–  aqueoussolution was used. A Y-shaped bypass was connected to make a staticflow of CH3COOH/NO2– solutionnear the blocking gel. 20 mL/min was used as an injection speed ofCH3COOH/NO2– solution.A cross-shaped fluidictest tube was assembled with transparentpolypropylene tubes and a four-way connector. Both tubes and the connectorare capable of operating in aqueous solutions ranging from the acidicto basic pH level. The inner radius of the four-way connector was1 mm. Water flowed through a vertical line at a rate of 30 mL/min.Other tubes perpendicular to the water flow line were connected tosyringes with chitosan/Cu4.62) wereapplied to the PDMS/glass device for 48 h. The microfluidic switchingtest was operated under similar conditions in 2+ solution  and flow rate (150 μL/min).A seven-hole microfluidicchannel was fabricated by patterningPDMS  on glass. The patterned PDMS was developedby a facile photolithography technique in order to control the channelstructure. The final dimensions of the microfluidic channel were fixedat 300 μm × 50 μm (width × depth). Permanentbonding between PDMS and the glass was obtained via a plasma bondingstep after rinsing these surfaces with an acetone/ethanol solution.Additional heat (60 °C) and pressure (6500 N/m


O centenário ECG ainda é uma excelente ferramenta para avaliar a atividade elétrica cardíaca. Ao longo das últimas décadas, o ECG tem sido renovado para acompanhar a evolução em outras áreas do conhecimento, como genética, biologia molecular e eletrofisiologia.Nossa experiência tem demonstrado que, entre o grande arsenal diagnóstico disponível para investigação de cardiopatias, o eletrocardiograma, ferramenta simples, prática, remota e rápida, é capaz de monitorar com precisão a extensão e a gravidade do acometimento cardíaco em diversos cenários.O intervalo QT e suas variações, muitas décadas após ter sido descrito pela primeira vez, ainda mantêm parâmetros relevantes para indicar se um paciente tem risco de apresentar eventos cardiológicos graves e às vezes fatais.Em 1856, o primeiro paciente com a síndrome do QT longo foi descrito por Meissner. Embora sua origem genética tenha sido estabelecida em 1901, foi somente em 1991 que Keating demonstrou pela primeira vez a associação de pacientes com síndrome do QT longo e a mutação do braço curto do cromossomo 11. Bazzet, em 1920, descreveu sua fórmula para a correção da frequência cardíaca do intervalo QT.O surgimento da pandemia da COVID-19 em março de 2020 mostrou uma doença inicialmente com sintomas respiratórios, mas com possível envolvimento de vários outros órgãos devido à sua resposta inflamatória bastante agressiva.Aproveitando a experiência no tratamento das repercussões cardíacas da COVID-19, os especialistas analisaram os achados eletrocardiográficos durante o período da infecção.No estudo feito por.. et al.,O grupo de estudo de 120 pacientes, 90 dos quais infectados com COVID-19 e 30 controles saudáveis pareados por idade e sexo, foi dividido em quatro grupos: I — controles saudáveis e pacientes com COVID-19: II — sem pneumonia, III — com pneumonia leve e IV — com pneumonia grave. Os resultados mostraram que um em cada cinco pacientes com COVID-19 apresentou lesão miocárdica.O estudo mostrou que nos casos de pneumonia grave existem claras alterações da repolarização ventricular. Apesar de valores de QT praticamente normais, a análise dos parâmetros estudados demonstrou aumento da dispersão da repolarização transmural, que é a etiologia usual das arritmias graves.As causas mais frequentes de mortalidade cardíaca em pacientes com COVID-19 foram eventos arrítmicos. Os tipos de arritmia foram diversos, com muitos aspectos relevantes. O mecanismo das arritmias não pôde ser caracterizado, mas a literatura relata a presença de fenômenos arrítmicos em 27,8% e de taquicardia ventricular/fibrilação ventricular (TV/FV) em 5,9% dos 187 pacientes estudados por Guo et al.O mecanismo mais importante das arritmias ventriculares relatado em pacientes com COVID-19 é semelhante ao das arritmias encontradas em pacientes com miocardite aguda. A análise das repercussões da miocardite aguda em outros estudos mostrou aumento dos intervalos QT, QTc e Tpe e das razões Tpe/QT e Tpe/QTc.No estudo discutido aqui, todas essas medidas aumentaram claramente com a gravidade da doença, como visto nos pacientes com COVID-19 e pneumonia grave.Confirmando relatos de maior frequência de arritmias em pacientes com níveis aumentados de troponina, o aumento nos níveis de troponina I de alta sensibilidade mostrou uma relação positiva e efetiva com as medidas dos parâmetros QT.Em um relatório recenteDano cardíaco (isquemia ou miocardite)ArritmiasNovo início ou agravamento de insuficiência cardíaca preexistenteDoença tromboembólicaAlterações cardíacas induzidas por tratamento médicoOs autores afirmam que “o envolvimento cardíaco em pacientes com COVID-19 se reflete em alterações de ECG como alterações de ST-T, prolongamento de QT, distúrbios de condução e arritmias ventriculares”. Assim, “os pacientes com sintomas cardíacos e anormalidades no ECG devem ser avaliados cuidadosamente para diagnosticar a COVID-19 — complicações cardíacas relacionadas, como miocardite, isquemia miocárdica ou arritmias graves”. Nesta pandemia, devemos manter essas suspeitas clínicas mesmo para pacientes que apresentam sintomas ou sinais discretos. Não há dúvida de que a presença de doenças cardiovasculares piora o prognóstico do processo. O vírus não pode ser considerado a causa de todas as complicações cardiovasculares, mas pode piorar ou revelar condições subjacentes precárias.No artigo aqui discutidoA presença de arritmias gerais  e malignas  também suscitou maior preocupação em casos com comprometimento miocárdico mais grave do que leve.A comparação do estudo de Haseeb et al., A presença de alterações isquêmicas, prolongamento do intervalo QT, distúrbios de condução elétrica e arritmias no ECG podem ser um grande sinal de alerta para orientar a conduta em caso de comprometimento cardiológico. The centennial ECG is still an excellent tool to assess electrical activity of the heart. ECG has been renovated over the last decades to keep pace with evolution in other areas of knowledge, such as genetics, molecular biology and electrophysiology.Our experience has demonstrated that, among the large diagnostic arsenal available to investigate heart diseases, the electrocardiogram, this simple, practical, remote and quick tool, is capable of accurately monitoring the extent and severity of cardiac involvement in various scenarios.QT interval and its variations, many decades after being first reported, still holds relevant parameters to indicate whether a patient is at risk for severe and sometimes fatal cardiological events.In 1856, the first patient with long QT syndrome was reported by Meissner. Although its genetic origin was established in 1901, it was only in 1991 that Keating first demonstrated the association of patients with long QT syndrome and short arm mutation of chromosome 11. Bazzet, in 1920, reported his formula for heart rate correction of the QT interval.The emergence of the COVID-19 pandemic in March 2020 showed a disease initially with respiratory symptoms, but with the possible involvement of several other organs due to its very aggressive inflammatory response.Taking advantage of their experience with treating the COVID-19 cardiac repercussions, experts analyzed electrocardiographic findings during the period of infection.Arquivos Brasileiros de Cardiologia, the authors examined the alterations of QT, QTc and Tpe (Ppeak-Tend) intervals, and the Tpe/QT and Tpe/QTc ratios, all of which are parameters of ventricular repolarization.In the study by Koc et al.The study group of 120 patients, 90 of whom infected with COVID-19, and 30 age-and-sex-matched healthy controls, was divided into four groups: I — healthy controls and COVID-19 patients: II — without pneumonia, III — with mild pneumonia, and IV — with severe pneumonia. Results showed that one out of five patients with COVID-19 had myocardial damage.The study showed that in cases with severe pneumonia there are clear ventricular repolarization alterations. In spite of practically normal QT values, analysis of the parameters studied demonstrated increased dispersion of transmural repolarization, which is the usual etiology of severe arrhythmias.The most frequent causes of cardiac mortality in patients with COVID-19 were arrhythmic events. The types of arrhythmia were diverse, with many relevant aspects. The mechanism of arrhythmias could not be characterized, but the literature reports the presence of arrhythmic phenomena in 27.8%, and of ventricular tachycardia /ventricular fibrillation (VT/VF) in 5.9% among the 187 patients studied by Guo et al.The most important mechanism of ventricular arrhythmias reported in patients with COVID-19 is similar to that of arrhythmias found in patients with acute myocarditis. The analysis of acute myocarditis repercussions in other studies showed increased QT, QTc and Tpe intervals, and Tpe/QT and Tpe/QTc ratios.In the study discussed here, all these measures clearly increased with disease severity, as seen in the COVID-19 patients with severe pneumonia.Confirming reports of higher frequency of arrhythmias in patients with increased troponin levels, increase in high-sensitivity troponin I levels showed a positive and effective relationship with the measures of QT parameters.In a recent report,Cardiac damage (ischemia or myocarditis)ArrhythmiasNew-onset or worsening of preexisting heart failureThromboembolic diseaseCardiac abnormalities induced by medical treatmentThe authors state that “cardiac involvement in COVID-19 patients is reflected in ECG alterations as ST-T alterations, QT prolongation, conduction disorders and ventricular arrhythmias.” Thus, “patients with cardiac symptoms and ECG abnormalities must be carefully assessed in order to diagnose COVID-19-related cardiac complications, such as myocarditis, myocardial ischemia or severe arrhythmias.”In this pandemic, we must maintain these clinical suspicions even for patients who present with discrete symptoms or signs. There is no doubt that the presence of cardiovascular disease worsens the prognosis of the process. The virus cannot be considered as the cause of all cardiovascular complications, but it can worsen or reveal precarious underlying conditions.In the article discussed here,The presence of general (16.7%) and malignant (11.5%) arrhythmias also raised greater concern in conditions with a more severe myocardial involvement than with mild involvement.Arquivos Brasileiros de CardiologiaComparison of the study by Haseeb et al.The presence of ischemic alterations, QT prolongation, electrical conduction disorders and arrhythmias in the ECG can be a big warning sign to guide management in case of cardiological involvement.


Branta canadensis) has been growing in residential and recreational areas, public concerns on potential acquisition of zoonotic pathogens from Canada geese and their faecal deposits have been increasing.As a population of non‐migratory Canada geese  demonstrated resistance to ≥1 antimicrobial agent.The targeted zoonotic pathogens were not identified by the faecal examinations performed. Of the 32 E. coli infections are potentially a public health concern although the prevalence was low in this study. Further, larger scale surveys are recommended.Targeted zoonotic pathogens were not detected among the examined resident Canada geese in North‐Central Oklahoma. The findings of multiple‐antimicrobial resistant  At eachAt each sampling visit, Canada geese were directly monitored for the moment of defecation for up to 2 h. Immediately after defecation by a goose was observed, a whole portion of freshly voided faeces was collected. When faeces was watery, a plastic disposable spoon was utilised. Although multiple samplings from the same goose at visit were avoided, identification or tracking of individual geese was not conducted in this study. The number of faecal samples collected per visit varied from four to 24 samples due to variable number of geese present at each site during the sampling. Individual faecal samples were stored separately in a plastic bag, and all samples were kept at 4°C until examinations.2.2Cryptosporidium spp. and other parasitic infections  was performed on each sample to detect the evidence of Soulsby, . In addi2.3Several faecal samples were removed from bacterial evaluations due to improper sample handling; thus, a total of 180 faecal samples were grouped into 36 pools and cultured for bacterial growth. Pools were made up of four (11 pools), five (14 pools) or six (11 pools) individual faecal samples recovered from the same location on the same day. All cultures were performed within 24 h of sample collections.2 environment. Cultures were monitored for bacterial growth for 2 days. A direct culture method was followed for Campylobacter spp. culture as this method has been evaluated and found to be useful for Campylobacter spp. enumeration  of pooled faecal sample was added into Tetrathionate Broth Base, Hajna (90 ml)  with 4% iodine . The mixture was incubated at 42°C for 2 days. After approximately 24 h of incubation, the broth mixture was streaked onto Xylose Lysine Tergitol‐4 (XLT‐4) and Brilliant Green (BG) agars . The XLT‐4 and BG agars were then incubated at 37°C for 24 h. The culture plates were observed for characteristic colonies of Salmonella spp. After 48 h of incubation, a second sample from the tetrathionate broth mixture was plated onto XLT‐4 and BG agars, incubated and observed for a characteristic growth of Salmonella spp. In addition to the targeted bacteria, any bacterial colonies observed were identified using a MALDI‐TOF Mass Spectrometer  following manufacturer's recommendations and recorded for data analysis.Aerobic culture was performed using 5% sheep blood agar and MacConkey agar  at 37°C in 5% CO2.4Escherichia coli isolates recovered from the 36 sample pools, using the Kirby Bauer Disk Diffusion method , Cryptosporidium spp. , Giardia spp.  and Salmonella spp. , were not identified in the faecal samples examined , Strongyloides spp. eggs , cestode eggs  and schistosome eggs . Coccidia, ascarid and strongylid infections were observed in all three counties, whereas cestode and Strongyloides spp. infections were identified in Payne and Oklahoma counties. Capillaria spp. and schistosome infections were found only in Oklahoma county and Payne county, respectively. Of 153 faecal samples that contained coccidian oocysts, one sample obtained from the L‐7 in Oklahoma City, Oklahoma county demonstrated Isospora spp. oocysts  demonstrated resistance to at least one antimicrobial agent. A total of 13 isolates  were resistant to one antimicrobial agent; 12 isolates were resistant to azithromycin and one isolate was resistant to tetracycline. Three isolates  were resistant to two antimicrobial agents belonging to different classes  and one isolate  recovered from the L‐3 in Stillwater, Payne county was resistant to five antimicrobial agents, including azithromycin, amoxicillin‐clavulanate, ampicillin, chloramphenicol and tetracycline. Many E. coli isolates  showed resistance to azithromycin  were detected in one of the faecal sample pools from location L‐11. The detection of yeast in low frequency from faeces of Canada geese as well as other avian species has been reported  transmitted by Canada geese and the freshwater snail, Gyraulus parvus, has been reported in Colorado Springs, Colorado . Anserobilharzia brantae adults are found in the blood vessels of Canada geese and produce eggs that are passed into the faeces  in 2019, our data in the current study did not consider seasonal or yearly differences. Additionally, one time faecal examination may not be sufficient to determine the prevalence of microorganisms in Canada geese due to intermittent shedding of Giardia spp. cysts  because animals were not directly or indirectly handled. All faecal samples were collected from the ground in the public areas.https://publons.com/publon/10.1002/vms3.791The peer review history for this article is available at


Oral squamous cell carcinoma (OSCC) is one of the malignant tumors with a poor prognosis. Periodontitis , their related genes (Hub genes), transcription factors (TFs), signaling pathways, enrichment functions, and compounds, and searching for genetic commonalities.The miRNAs expression datasets of OSCC and PD were searched from the GEO database. The miRNA and related crosstalk mechanism between OSCC and PD was obtained through a series of analyses.ZNF460, FBN1, CDK6, BTG2, and CBX6, while the most important dysregulation TF includes HIF1A, TP53, E2F1, MYCN, and JUN. 5-fluorouracil, Ginsenoside, Rh2, and Formaldehyde are the most correlated compounds. Enrichment analysis revealed cancer-related pathways and so on.hsa-mir-497, hsa-mir-224, hsa-mir-210, hsa-mir-29c, hsa-mir-486-5p, and hsa-mir-31are the top miRNA nodes in Co-DEmiRNA-Target networks. The most significant candidate miRNA dysregulation genes are The comprehensive analysis reveals the interacting genetic and molecular mechanism between OSCC and PD, linking both and providing a foundation for future basic and clinical research.The online version contains supplementary material available at 10.1186/s12903-022-02704-2. Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignant tumors, with a high incidence of 350,000 new cases and 170,000 deaths , drinkinThere is a convincing correlation between inflammation and the occurrence and development of many cancers –11. The MicroRNA (miRNAs) are small RNAs that play vital roles in regulating gene expression. miRNAs regulate cellular physiological processes by regulating expression and play a crucial role in mediating diseases . The molThis study aimed to comprehensively analyze differentially expressed miRNAs (DEmiRNAs) in OSCC and PD to identify candidate CO-DEmiRNAs, their associated hub genes, signaling pathways and related compounds. Thereby promoting the understanding of the shared molecular mechanisms between closely related tumors and non-neoplastic diseases. And providing a theoretical basis for driving future basic research and clinical practice.In more than 20 years of clinical work by our group, we found that almost all patients with OSCC suffer from periodontitis while burdening the tumor. Based on our previous translational studies on inflammation-precancerous lesion cancer, we sought to explore whether the presence of crucial genetic molecules could serve as a connecting key for PD and OSCC. Recent studies have revealed numerous noncoding RNAs (ncRNAs) roles in cancer and various diseases, highlighting the biological significance of these previously “neglected” RNA species. In particular, microRNAs (miRNAs) are involved in many biological processes that affect cell homeostasis. MiRNAs are considered post-transcriptional gene regulators that can achieve translational repression, mRNA degradation, and gene silencing and play a significant role in gene expression. We sought to explore and determine whether there are co-expressed key miRNAs and transcription factors present in PD and OSCC by bioinformatics methods, thus providing a solid basis for our subsequent target findings. This helps us in a series of studies in stomatitis-cancer transformation. We promote an understanding of the shared molecular mechanisms between closely related tumors and non-neoplastic diseases. We provide a theoretical basis for future basic research and clinical practice.https://www.ncbi.nlm.nih.gov/geo/). Only one OSCC miRNA dataset GSE45238 was identified for analysis . For the miRNA expression dataset for PD, we chose the most numerous GSE54710 . All experiments were performed further with relevant guidelines and regulations.Download the miRNA expression datasets of OSCC and PD from the GEO database Table  (https:/https://www.r-project.org/). The data were corrected using the “ComBat” method in the R package “SVA.” The R package “Limma” was then used to identify miRNAs significantly differentially expressed in OSCC and PD cases and controls. miRNA  are regarded as “DEmiRNA” and used for analysis. Furthermore, LogFC > 0.5 is overexpressed and LogFC < 0.5 is low expressed.The microarray and expression data were downloaded using the R package “GEOquery”  as Co-DEmiRNAs and excluded Shared DEmiRNAs with different expression trends .https://www.mirnet.ca/). For the Co-DEmiRNA-Gene network, target genes were selected from 3 packages (TarBase v8.0), miRTarBase v8.0 (http://mirtarbase.mbc.nctu.edu.tw/php/index.php), and miRecords (http://c1.accurascience.com/miRecords). Due to poor stability, “Steiner Forest Network” cannot achieve the most stable link on the premise of ensuring the correlation. Instead, “Minimum Network” was chosen, which reduces the network complexity and retains key features that demonstrate network connectivity. It is computed using the critical nodes of all elements. To build the “Minimum Network”, the shortest paths between the nodes are determined, and any nodes not on the shortest path are removed.The co-DEmiRNA target network was constructed using miRNet 2.0 , TransmiR v2.0 (http://www.cuilab.cn/transmir) to download the corresponding transcription factors (TF) of Co-DEmiRNAs, extracted the corresponding TFs, and constructed a Co-DEmiRNA-TF Network using a similar method. The Co-DEmiRNA-TF networks were further subjected to functional enrichment analysis using the KEGG pathway, Reactome pathway, and GO.We used multiple databases such as miRbase (http://ctdbase.org/), miRbase (https://www.mirbase.org/), SM2miR (http://bioinfo.hrbmu.edu.cn/SM2miR/) and PharmacomIR.Search for small-molecule compounds with a high correlation with Co-DEmiRNAs. Build the Co-DEmiRNA-compound network based on data from CTD datasets  HNSC (Head and Neck Squamous Cell Carcinoma) project were selected for verification, and the corresponding data without clinical information were discarded. Samples belonging to oral cancer sites  were retained in clinical information, and samples from nonoral cancer sites  were excluded. The miRNA-seq data in RPM (Reads per Million mapped reads) format was converted to log2, and 373 samples were obtained . To calculate the area under the curve, the area value under the ROC curve should be between 0.5 and 1. The closer the AUC is to 1, the better the diagnostic effect.Other databases were used to verify the diagnostic efficacy of the best Co-DEmiRNA as a diagnostic marker. The miRNA-seq data of the level 3 BCGSC miRNA Profiling in the TCGA , the comparison was between the cases of OSCC (tumor specimens of OSCC patients) and normal cases (adjacent nontumor epithelium). After correction, 858 miRNAs were retained, and 208 OSCC-related significant DEmiRNAs were identified. In periodontitis data GSE54710), the comparison was the case of periodontitis  and standard samples . In contrast, PD dataset analysis retained 1368 miRNAs and identified 54 significant PD-related DEmiRNAs . A Co-DEmiRNA-Compound minimum network was constructed, consisting of 9 compounds and 11 miRNAs with 23 edges  and Fusobacterium nucleatum (F. nucleatum), have played an essential role in oral cancer occurrence [The miRNA is an essential intermediate hub of host physiological and pathophysiological activities . We knowcurrence , which rOur current study explored the epigenetic mechanism of CO-DEmiRNA mediated the association between OSCC and PD by screening and identifying Co-DEmiRNA common in the two diseases. The network architecture was applied to determine DEmiRNA-related hub genes and TF, which could be used as the linkage mechanism of differential expression and further function of DEmiRNA. In addition, functional enrichment analysis was conducted on them to determine key pathways, molecular functions, and cell components. In addition, the small molecule compounds associated with Co-DEmiRNA were analyzed, and the key junction compounds between OSCC and PD were explored. The key Co-DEmiRNAs identified in this study may provide more effective guidance in the future study of inflammation-cancer transformation.Most DEmiRNAs had the same expression trend in the two diseases, which further revealed the similar immune mechanism of the host oral microenvironment against inflammation or cancer, perhaps a common pattern of miRNA dysregulation in pro-inflammatory and pro-cancer responses. Co-DEmiRNAs with the highest degree included hsa-mir-224, hsa-mir-210, hsa-mir-31(overexpressed), and hsa-mir-497, hsa-mir-29c, hsa-mir-486(which were low expressed). They are all broadly involved in inflammation, cancer, and host immune responses.hsa-mir-224 is considered an early diagnostic marker of cancer . hsa-mirZNF460, FBN1, CDK6, BTG2, and CBX6, which may be the essential hub genes/mediators between OSCC and PD. ZNF460 (zinc finger protein 460) is involved in the regulation of multiple cancer processes by JAK2/STAT3 pathway [FBN1 (fibrinin-1) is a common extracellular matrix encoding gene [FBN1 inhibits TGF-β 1-mediated expression of Periosteum, thereby inhibiting collagen fiber production. In addition, FBN1 also plays an important role in the Wnt/β-catenin signaling pathway that regulates cancer cell migration [CDK6 (cyclin-dependent kinase 6), as one of the proto-oncogenes driving tumors, has become a key target of various cancer therapies [CDK6 also inhibits the proliferation of periodontal ligament cells (PDLCs) by regulating the cell cycle in periodontitis [BTG2 (B cell translocation gene 2) has long been recognized as a tumor suppressor gene in various cellular processes [BTG2 inhibits cancer migration, invasion, EMT and, glycolysis [CBX6 (chromobox protein 6) accelerates EMT in head and neck squamous cell carcinoma [Our study revealed that dysregulation of associated gene expression mediated by noncoding RNA represented by miRNA might be the key mechanism linking PD to OSCC or other cancers. The genes with the highest degree in the Co-DEmiRNA-Gene network include  pathway , and its pathway , 40. FBNing gene , and inaing gene , a uniquigration . CDK6  can promote gingival tissue aging and hypoxia stress  and incrFunctional enrichment analysis of Co-DEmiRNA-Gene, Hub genes and TF networks showed that many cancer-related KEGG/Reactome pathways are enriched, supporting previous findings that PD is a significant risk factor for OSCC . Ras protein signal transduction and the functional enrichment of transcription factor binding in GO analysis are very obvious. These play a crucial role in inflammation, immunosuppression, and antitumor immunity –69.In this study, the compounds most closely related to Co-DEmiRNA of the two diseases were also analyzed. 5-fluorouracil(5-FU), Ginsenoside, Rh2, and Formaldehyde are the small molecule compounds with the strongest correlation with Co-DEmiRNA. miRNAs reduce the resistance of oral squamous cell carcinoma cells to 5-fluorouracil . At the This study investigated the epigenetic mechanism linked between OSCC and PD, including multiple aspects, such as DEmiRNA, Co-DEmiRNA, Hub gene, TF, and even related compounds. The main limitation is the lack of further experimental data to validate these candidate key linking mechanisms. The datasets used in this study were from a single database, which may limit the accuracy of the results. Future-related research using diverse composite data is critical and necessary. Another point is that other noncoding RNAs, such as lncRNAs, circRNAs, and sncRNAs, may also play an important role in the pathogenic mechanism of OSCC and PD, which were not investigated in this study. Therefore, future studies may further investigate other noncoding RNAs as linkage mechanisms. Future studies should aim to validate the further link between Co-DEmiRNA Hub genes, TF pathway, and compound, these key parts between OSCC and PD, using clinical studies, in vitro and in vivo experiments, etc. In addition, since this association may be bidirectional, it is necessary to comprehensively study the biological mechanisms involved, which will also provide a basis for us to explain the inflammation-cancer transformation further.ZNF460, FBN1, CDK6, BTG2, CBX6) and TFs . It highlighted the most DEmiRNA-related small molecule compounds . These findings provide a theoretical basis to guide future experimental research.Comprehensive analysis of Co-DEmiRNAs in OSCC and PD revealed key genetic molecular mechanisms Table , includiAdditional file 1. Table S1a. Differentially Expressed miRNA in Oral Squamous Cell Carcinoma (GSE45238). Table S1b. Differentially expressed miRNA in Periodontitis (GSE54710). Table S2a. Co-DEmiRNA-Gene Minimum Network. Table S2b. KEGG Pathway Enrichment Analysis of Co-DEmiRNA-Gene Network. Table S2c. Reactome Pathway Enrichment Analysis of Co-DEmiRNA-Gene Network. Table S2d. Gene Ontology-Biological Process Enrichment Analysis of Co-DEmiRNA-Gene Network. Table S2e. Gene Ontology-Molecular Functions Enrichment Analysis of Co-DEmiRNA-Gene Network. Table S2f. Gene Ontology-Cellular Component Enrichment Analysis of Co-DEmiRNA-Gene Network. Table S3. The Transcription Factors of 11 Co-DEmiRNA. Table S4a. Co-DEmiRNA-TF Minimum Network. Table S4b. KEGG Pathway Enrichment Analysis of Co-DEmiRNA-TF Network. Table S4c. Reactome Pathway Enrichment Analysis of Co-DEmiRNA-TF Network. Table S4d. Gene Ontology-Biological Process Enrichment Analysis of Co-DEmiRNA-TF Network. Table S4e. Gene Ontology-Molecular Functions Enrichment Analysis of Co-DEmiRNA-TF Network. Table S4f. Gene Ontology-Cellular Component Enrichment Analysis of Co-DEmiRNA-TF Network. Table S5. Co-DEmiRNA-Compound Minimum Network.