The Binge Eating Scale (BES) is a widely used measuring tool to assess binge eating problems in Western countries. However, the psychometric properties of such scales among cross-cultural youth groups are insufficient, and the factor structure continues to be debated; therefore, further research is needed. The aim of this study was to examine the properties of BES among overweight college students in Taiwan.A cross-sectional design and convenience sampling were adopted to recruit 300 overweight students from five universities. A translated Traditional Chinese version of BES was used for the survey, and the validity of the scale was tested using the Confirmatory Factor Analysis (CFA) and Bulimic Investigatory Test, Edinburgh (BITE). The reliability was evaluated using internal consistency and test–retest reliability.The CFA results showed a reasonable model fit. The first-order two-factor model was consistent with that of the original BES and significantly correlated with the criterion of BITE score. Cronbach’s α value, representing internal consistency reliability, and the intraclass correlation coefficient of repeated measures made one month apart were both 0.83, indicating good reliability and stability. Significant correlations were observed between the BES score and sex and BMI; however, no correlation was observed between BES scores and age.The BES presents sound psychometric properties, has good cross-cultural applicability, and can be used as a first-line screening tool by mental health professionals to identify the severity of binge eating behavior among overweight college students in Taiwan. It is recommended that participant diversity and obesity indicators be incorporated into the scale in the future to establish a universal psychometric tool.The online version contains supplementary material available at 10.1186/s40337-023-00774-3. The Binge Eating Scale (BES) is a screening tool that has been widely used to assess binge eating problems in Western countries. The current study aimed to test the validity and reliability properties of the BES among overweight college students in Taiwan. This research involved 300 overweight and obese college students while using a traditional Chinese-translated questionnaire in the survey and analyzed with subjective and scientific statistics methods afterward. The results indicated that BES has good cross-cultural applicability and can be used as a first-line measuring tool by mental health professionals to identify the severity of binge eating behavior among overweight or obese college students in Taiwan.The online version contains supplementary material available at 10.1186/s40337-023-00774-3. Binge eating disorder (BED) is the most common type of eating disorder and is one mental illness with rather high morbidity . A nation = 189) of those who participated in weight-loss courses in hospitals revealed binge eating symptoms, most of whom were young and had early-onset obesity and psychological distress  recommendations. The diagnostic criteria for overweight  and specificity (81.8%), indicating that the scale could effectively predict BE symptoms. The results indicate that the BES presents sound psychometric properties, has good cross-cultural applicability, and can be used as a first-line screening tool by mental health professionals to identify the severity of binge eating behaviors among overweight college students in Taiwan. It is recommended that participant diversity and obesity indicators be incorporated into the scale in the future to establish a universal psychometric tool.Additional file 1. Appetite Scale.


Novel techniques and technologies have shown increased survival in large TBSA burns, however, challenges with meaningful quality of life and functional outcome pose a concern. Dermal substitute and skin cell suspensions provide an area of ongoing investigation to reduce morbidity from scars, loss of functionality from contractures, and need for further procedures. This study is a follow up on the use of a dermal substitute along with autologous skin cell suspension (ASCS) with long term physical and mental outcomes as assessed with the Burn Specific Health Scale in two survivors of greater than 90% TBSA full-thickness burns.We report on two 18-year-old patients treated with the use of allograft, dermal substitute, and ASCS with split-thickness skin grafts (STSG) to achieve coverage of >90% burns. Patient 1 initially had full-thickness “leathery” burns, sparing only the plantar and dorsal aspect of the feet and patient 2 had fourth-degree burns in most areas with only the groin and feet spared. The patients’ clinic visits were reviewed and both patients agreed to participate in the Brief Burn Specific Health Scale (BSHS-B) questionnaire three-years post discharge. The survey responses of each patient were separated into their respective BSHS-B health domains and a raw Health-related quality of life (HRQOL) score was calculated for each domain.Patient survey responses were categorized into their respective domains: interpersonal relationships, simple abilities, affect, body image, sexuality, hand function, treatment regimens, heat sensitivity, and work. We observed in both patients that the hand function and heat sensitivity domains of the patient’s BSHS-B were the lowest scoring in their survey responses, while the interpersonal relationships and simple abilities were the highest scoring. 15 months post discharge the patients’ bilateral upper extremities had 130° of flexion, 80° of supination, and 80° of pronation with no instability of the elbow. Both patients were continuing to work with physical therapy and were able to ambulate in their own home.Appropriate psychosocial management in addition to aggressive targeted surgical management and regular post-discharge clinical follow-ups were noted to have contributed to the improved post-operative outcomes in this patient with extensive burns. The findings reported in this follow-up case series demonstrate the promise of utilizing a dermal substitute and ASCS with STSG in acute surgical management of patients with extensive burns. This follow-up study demonstrates the importance of aggressive physical rehabilitation and psychosocial management in these patients’ post-operative course of recovery.The findings reported in this follow-up case series suggest the importance of dermal substitute and ASCS is the enhanced positive psychosocial domains and adequate cosmetic appearance along with enhanced physical healing.


Toddlers exposed to persistent comorbid anxiety and mood disorders scored significantly higher on the cognitive (p = 0.049), motor (p = 0.013) and language (p = 0.041) domains and attained significantly higher fine motor (p = 0.043) and gross motor (p = 0.041) scaled scores compared to toddlers with no maternal mental health disorder exposure. Future investigations should focus on the role of protective factors to explain the pathways through which maternal mental health status is associated with positive toddler neurodevelopmental outcomes.One of the biggest threats to early childhood development in Africa is poor maternal mental health. The present study reports on the relationships between clinical diagnoses of persistent maternal mental health disorders (at 3- and/or 6- and 18-month post-term age) and toddler neurodevelopment at 18 months of age. Eighty-three mother–toddler dyads from low socio-economic status settings in Cape Town, South Africa, were included. At the 3-, 6- and 18-month postnatal visits, clinician-administered structured diagnostic assessments were carried out according to the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria. Toddler neurodevelopment at 18 months corrected age was assessed with the Bayley Scales of Infant and Toddler Development (BSID-III). No significant differences ( The transition from early infancy to toddlerhood is a time of remarkable brain development and growth. A child’s neurodevelopment encompasses several developmental domains, namely cognitive, language, motor, social-emotional and adaptive behaviour . The sucOne of the biggest threats to a nurturing home environment and early childhood development is poor maternal mental health ,9. AccorThe current study aimed to address this gap by assessing the relationships between distinct clinical diagnoses of persistent maternal mental health disorders (at 3- and/or 6- and 18-month post-term age) and toddler neurodevelopment across five developmental domains at 18 months of age. This is a longitudinal follow-up study of a cohort of mother–infant dyads living in poor urban and peri-urban communities in Cape Town, South Africa. Our previous analyses revealed no significant differences on any of the domains of the Bayley Scale, Third Edition (BSID-III)  domains The objectives of the current study were to examine the associations between persistent (i) maternal mood disorders; (ii) maternal psychotic disorders; and (iii) comorbid maternal anxiety and mood disorders (at 3 and/or 6 months and 18 months) and the motor, cognitive, language, social-emotional and adaptive behavioural domains of 18-month-old toddlers.The current longitudinal study formed part of a larger prospective cohort design, the Maternal and Infant Mental Health (MIMH) study. The MIMH study recruited participants from Stikland Psychiatric Hospital, a specialist psychiatric facility that provides services to largely low socio-economic communities, and a private-funded Well Baby follow-up clinic in the northern suburbs of Cape Town, South Africa. The data for the current sub-study are derived from Stikland Hospital. Neurodevelopmental follow-up assessments of the 18-month-old toddlers included in the current study were conducted at 3- and 6-months corrected age, and the procedures and findings have been reported elsewhere ,23. The Pregnant women aged 18 years and older attending the Maternal Mental Health Outpatient Clinic at Stikland Hospital with a previous or current diagnosis of psychiatric illness [according to the DSM-V  criteriaIn the comparison group, the same inclusion and exclusion criteria applied, and only mother–child dyads with no antenatal or postnatal exposure to mental health illnesses were included. The comparison group resided in the same low-income communities as the rest of the study cohort. Obstetric nurse practitioners at community health clinics and day hospitals recruited the comparison group within the first week after the infants were born. Since no previous maternal medical history records were available, the prenatal medical and psychiatric history was obtained from the mothers. Trained research assistants obtained written informed consent from mothers in their language of choice. Informed consent was obtained during the enrolment of mothers at Stikland Hospital.Trained research staff collected comprehensive health data from maternal and toddler hospital records and the Children’s Road to Health booklets  and fromThe BSID-III was used to assess neurodevelopment at 18 months post-term age . The BSIA trained paediatric physiotherapist (the first author) administered the BSID-III. She was blinded to the maternal mental health diagnoses and the toddlers’ prenatal, perinatal and postnatal medical history. The cognitive, motor and language domains were assessed by direct observation in the child’s preferred language  with instructions consistent with administration and scoring directions set out by the manual. The social-emotional and adaptive behaviour subscales were assessed through observation of the toddler and maternal reports. Assessments were conducted in a standard testing environment  with ample space for the toddlers to demonstrate gross motor skills such as running, stair climbing and jumping. Only the assessor, the toddler and the mother were present during the assessment to minimise any distractions. It took 60 to 90 min to administer the five domains of the BSID-III. We scheduled assessments to fit into the child’s sleeping and eating patterns to avoid factors such as tiredness or hunger influencing test results. Testing was rescheduled within the same week if it was impossible to administer the tests within one session because the child was fatigued, restless and/or upset. The BSID-III provides composite scores for cognitive, motor and language skills as well as social-emotional and adaptive behaviour . Separate scaled scores are provided for fine and gross motor and expressive and receptive language subscales . Composite scores were categorised as above-average (standardised score > 115), average (>85), delayed (70–84) or severely impaired (<70) performance. Scaled scores were classified as above-average (>13), average (8–12) and below-average (≤7) performance. Toddlers scoring ≤ 1 SD below the mean of the composite (<85) or scaled (≤7) scores were classified as demonstrating a clinically significant developmental delay. Except where otherwise stated, motor development refers to combined gross and fine motor development and language development to combined expressive and receptive language development.At the 3-, 6- and 18-month postnatal visits, clinician-administered structured diagnostic assessments as per standard of care were carried out to assess maternal mental health. A qualified senior psychiatrist with at least five years’ experience conducted the assessments in English or Afrikaans. In cases where IsiXhosa-speaking women were unable to communicate in either English or Afrikaans, a trained translator assisted. Psychiatric diagnoses were made according to the DSM-V diagnostic criteria . AdditioApproval for this study was obtained by Stellenbosch University’s Health Research Ethics Committee (S12/04/111). Permission was obtained from the study’s site  and the Western Cape Provincial Health Research Committee . All mothers provided written informed consent and were informed that they could exit the study without affecting the further standard of care.Statistical analysis was performed using the Statistical Analysis System (SAS) 9.4 software, SAS Institute Inc., Cary, NC, USA. Maternal and child socio-demographic and health characteristics were described for the mental health disorder groups using either medians, lower and upper quartiles or numbers (%), whichever were appropriate. Similarly, descriptive statistics were provided for the BSID-III scales, which comprised composite scores for the motor, cognitive, language, social-emotional and adaptive behavioural domains and scaled scores for the fine and gross motor and the expressive and receptive language subscales. Due to small samples for two of the maternal mental health disorder groups (n = 13 for psychotic disorder and n = 9 for comorbid anxiety and mood disorders), Kruskal–Wallis tests were conducted to compare the BSID-III composite and scaled scores between the maternal mental health disorder groups and the comparison group. Furthermore, due to small sample sizes, it was not possible to conduct modelling with relevant mother–toddler socio-demographic and health covariates as confounders.The socio-demographic and health characteristics of the mothers and toddlers who participated are presented in None of the toddlers exposed to HIV during pregnancy were HIV infected. None of the toddlers in the comparison group were born preterm (<37 weeks gestation), while four toddlers exposed to mood (13.3%), one toddler exposed to psychotic (7.7%) and one toddler exposed to comorbid anxiety and mood (11.1%) disorders were born moderately to late preterm . Three toddlers had a history of postnatal hospitalisation before three months post-term age; one with an Escherichia coli infection (exposed to psychotic disorders), one with a respiratory tract infection (exposed to mood disorders) and one with jaundice (exposed to anxiety disorders). Apart from one toddler (exposed to psychotic disorders) that presented with chronic tonsilitis, the medical history of the toddlers was unremarkable, and none had been hospitalised between 3 and 18 months post-term age. None of the toddlers’ weight-for-age z score (WAZ) or head circumference-for-age z score (HCAZ) was below −2 at 18 months post-term age. p = 0.049), motor (p = 0.013) and language (p = 0.041) composite scores as well as fine motor (p = 0.043) and gross motor (p = 0.041) scaled scores compared to toddlers with no maternal mental health disorder exposure. No significant differences (p > 0.05) were found between toddlers with exposure to persistent maternal mood or psychotic disorders on the different BSID-III domains and subscales and toddlers without exposure. None of the included toddlers scored below 85 (delayed performance) or 70 (severely impaired) on the social-emotional composite score.The number of toddlers (n = 15) that presented with a clinically delayed and/or severely impaired performance on the various domains and subdomains of the BSID-III are summarised in The current prospective study is one of the first to investigate whether clinical diagnoses of persistent mental health disorders of mothers residing in low-income communities in Cape Town, South Africa, were associated with various neurodevelopmental domains in 18-month-old toddlers. No significant differences were found between toddlers with and without exposure (comparison group) to persistent and concurrent maternal mood disorders (n = 30), as measured at 3 and/or 6 months and 18 months post-term on any of the domains and subscales of the BSID-III. This contrasts with earlier and recent findings in HICs. Cornish et al. (2005) reported significantly lower motor and cognitive performance on the BSID-II in 15-month-old toddlers exposed to persistent mood disorders throughout the first 12 months post-term and beyond . The autAlthough toddlers exposed to maternal psychotic disorders (n = 13) presented with the lowest scores on the cognitive, motor and language domains, they did not score significantly lower on any of the domains and subscales of the BSID-III compared to toddlers with no exposure. Previously, we reported that 6-month-old infants with exposure at 3 and 6 months to persistent psychotic disorders scored significantly lower on the motor and cognitive domains of the BSID-III . Our curContrary to expectations, the small group of toddlers exposed to persistent anxiety disorders (n = 9) attained significantly higher cognitive, motor and language composite scores and fine motor and gross motor scaled scores compared to toddlers with no maternal mental health disorder exposure. These findings were unexpected since seven of the nine mothers had received a diagnosis of comorbid anxiety and mood disorders, while two mothers had been diagnosed with anxiety disorders only. This is clinically important since experiencing comorbid anxiety and mood disorders such as depression involves more severe and persistent symptomatology and functional impairment than experiencing either disorder alone ,40. FurtEven though the literature suggests that comorbid anxiety and depression may have a negative impact on infant development , the potMethodological differences between the current study and earlier longitudinal studies on the effect of persistent maternal mental health disorders and toddler outcomes may explain the contrasts in findings. Previous studies have based their findings on standardised self-reported questionnaires or screening tools for depressive and/or anxiety symptoms ,47,48,49There is a strong relationship between poor nutritional status and adverse child neurodevelopment. A meta-analysis reported a significant association between maternal depressive symptoms  and early childhood underweight and stunting in LMICs . FurtherAll mothers with psychiatric diagnoses in our study attended Stikland Maternal Mental Health Outpatient Clinic and received a patient-specific therapeutic intervention. Although none of these interventions were specifically geared to improving mother–child relationships  or parenting behaviour and practices, mothers may have developed coping strategies and support structures that could perhaps have a constructive impact on the development of their children in the presence of poor mental health. Some of these coping strategies or modifiable factors that may have a buffering effect against developmental delays in the presence of poor maternal mental health are dependable and healthy interpersonal relationships, reliable social support networks, maternal optimism, higher education and effective strategies to balance work, household and family responsibilities . The facAlthough typical for studies including a cohort with a clinical diagnosis of psychiatric disorders, a limitation of our study was the small sample size, in particular, the maternal comorbid anxiety and mood disorder and psychosis subgroups; therefore, our findings should be treated as preliminary. Due to the small sample sizes of the different subgroups, it was not possible to analyse socio-demographic and health characteristics as potential confounders in the pathway of toddler neurodevelopmental outcomes. There are higher rates of living in extended households, which include multigenerational family structures, in poorer areas in South Africa . In factThe present study contributes to the limited research in LMICs on the neurodevelopmental outcomes of toddlers exposed to a clinical diagnosis of persistent maternal psychopathology in Africa. Our study presents novel evidence of the effect of persistent mood, psychotic and comorbid anxiety and mood disorders on multiple domains of toddler neurodevelopment. The findings that persistent exposure to mood, psychotic and comorbid anxiety and mood disorders did not have an adverse impact on toddler cognitive, motor and language development and toddler social-emotional and adaptive behaviour are reassuring for women with a clinical diagnosis of mental health disorders in our setting. However, due to the small sample sizes of maternal mental health disorder subgroups and the paucity of comparable research studies on this topic, it is much too soon to conclude that toddlers exposed to persistent mental health problems will not encounter neurodevelopmental problems in other settings and populations or at a later stage. Therefore, follow-up of similar larger cohorts is important to study the short- and long-term effects of exposure to persistent mental health disorders on the neurodevelopmental outcome of toddlers and older children. Since we found that toddlers exposed to comorbid anxiety and mood disorders presented with significantly higher cognitive, motor and language composite scores, future comprehensive investigations should focus on the role of possible protective or risk factors to understand, recognize and explain the pathways through which maternal mental health status is associated with toddler neurodevelopmental outcomes. Since extended households may play a significant role in the care of young infants and children in LMICs, future research should focus on the role of extended family members in providing a nurturing home environment for infants and toddlers.


Society’s sleep-wake cycle and eating behaviors have altered as the psychological outcomes of the COVID-19 pandemic.The aim is to examine the relationship between sleep-wake rhythms, eating behaviors  and ADHD symptoms with weight gain during the COVID-19 pandemic.Participants were 578 female university students divided into three groups based on weight change during COVID-19 who lost weight (WL), those whose weight did not change (nWC), and who gained weight (WG). They completed an online survey including, a consent form regarding voluntary participation, the socio-demographic form in which requested information about weight change in the last year, the Pittsburg Sleep Quality Index (PSQI), Eating Attitudes Test, Adult ADHD Severity Rating Scale, Wender Utah Rating Scale. The study was approved by the Selçuk University Local Ethics Committee (Decision Number: 2021/369).The sleep-wake phase was more delayed in WGs compared to the other two groups. The bulimic behavior score was higher and the oral control behavior score was lower in the WG group than in the nWC group. In the first step of the hierarchical regression analysis to determine factors associated with weight change, childhood and current ADHD symptoms did not show an association with weight change. In the second step, sleep-wake parameters were added to the analysis, and mid-sleep time was a strong predictor of weight gain . In the third step, in which disordered eating behaviors were added to the analysis, bulimic behaviors  were associated with weight gain and oral control behaviors  were associated with weight loss.WGs had a delayed sleep phase more than nWCs and WLs in the one-year period during the COVID 19 outbreak. Chronotherapeutic approaches that regulate sleep-wake rhythm may facilitate weight control of individuals during stressful periods such as COVID-19 outbreak.None Declared


Plant–insect interaction is a fast-developing research field that continues to increase the interest of numerous scientists, many of whom come from heterogeneous backgrounds. This variety reflects the complexity and the multifaceted associations from which plants and insect interactions may originate.Mutualism, pollination, and biotrophy boost the co-evolution of plant and insect responses. In the case of antagonistic associations, plants have evolved defenses against various insect feeding strategies, which are counterbalanced by the ability of insects to detoxify plant chemicals or to react specifically to plant compounds. The success of plants in withstanding insect herbivory depends on their ability to quickly recognize and decipher the incoming signal and adequately respond to a wide array of attacking herbivores. Whilst this topic has been widely investigated, less attention has been paid to how insects use plant signals to their own advantage to detect high-quality food, choose where to lay their eggs, or find their prey.Current research on plant–insect interactions has mainly focused on genomics and proteomics, which are late events induced by biotic stress. Early events, within the first seconds to minutes, are responsible for the recognition and triggering of the signal transduction pathways, preceding both genomic and proteomic responses. For both plants and insects, sensing and communication are key features that can improve fitness and grant survival in contrasting environments.Understanding how plants counteract herbivore aggression equals our understanding of insect herbivores’ defense against plant countermeasures. In this Special Issue, we explore the genomics and metabolomics of plant–insect interactions with a collection of 19 papers focusing on the effects of some of the most devastating herbivores on their host plants, including planthoppers, thrips, and aphids, among others.PDF1.2 and abscisic acid (ABA)-responsive UDP-D-glucuronate 4-epimerase 6 (GEA6) in Arabidopsis thaliana [2+ and H2O2—to the activation of phytohormone pathways and the attraction of herbivores’ predators through the emission of herbivore-induced volatile organic compounds (HIVOCs). This review introduces several aspects that are deeply explored in the papers comprising this Special Issue.Gen-ichiro Arimura and co-workers focus on the nature of the transcriptional regulation of the jasmonic acid (JA)-responsive plant defensin gene Nilaparvata lugens, BPH) with resistant and susceptible rice varieties reveals differentially accumulated metabolites (DAMs) and expressed genes (DEGs) with flavonoids and salicylic acid and genes related to stimulus, with them being upregulated in the resistant variety [The paper by Guangcun He and co-workers on the interaction of the brown planthopper  by using both double-stranded RNA SFMLP (dsSFMLP) and SFMLP gene knockdown [In the white-backed planthopper (WBPH), nockdown . Their rMyzus persicae, show high resistance to pesticides, which has prompted the search for new environmentally-friendly bioactive molecules to control this pest. Francisca Blanco-Herrera and co-workers showed that pectin-derived oligogalacturonides (OGs) improve Arabidopsis’ performance against M. persicae by identifying defense mechanisms involving the production of callose and ROS and the expression of genes related to the salicylic acid (SA) signaling pathway [Aphids, with particular reference to the generalist  pathway . The treM. persicae and Acyrthosiphon pisum [Marilyne Uzest and co-workers studied the acrostyle, an aphid organ that produces stylin proteins able to bind to plant viruses transiently. They found that a salivary effector (Mp10), which aphids inject into the plant’s cytoplasm during feeding, can bind the acrostyle by probably interacting with stylin-03 of both on pisum . By usinA. pisum’s feeding activity has been studied through its interaction with wild-type pea in the context of climate change, with particular reference to elevated CO2 (eCO2) levels. Christine H. Foyer and co-workers showed that the phytohormones strigolactone (SL) and gibberellin are involved in host susceptibility in pea–A. pisum interaction, but the aphid–plant compatibility control of these phytohormones is not changed by eCO2 [ by eCO2 .Spodoptera exigua to visit different plant species and analyzed the pollen attached to migratory individuals, which at the larval stage are major crop pests [Plant interactions with pollinators imply the perception of insects, the induction of early signals and responses, short- and long-distance signal transduction, phenotypic changes, and the ability of the insect to co-evolve intricate patterns of associations with plants. Kongming Wu and co-workers reported on the ability of the moth op pests . The autS. littoralis herbivory has been studied by focusing on CALMODULIN1 (CAM1) and WRKY53 function. Yingbai Shen and co-workers [LOX3) and lipoxygenases 4 (LOX4) by negatively regulating their gene expression. Eventually, the plant resistance to herbivory is negatively regulated by CAM1 and WRKY53 through regulation of the JA biosynthesis pathway. These results underline the role of WRKY53 in plant resistance to insects.The resistance of Arabidopsis to -workers  confirmeHelicoverpa armigera (namely the pod borer) is known for being one of the major species responsible for crop losses. Rohini Sreevathsa and co-workers analyzed the flavonoid biosynthesis in one of the pigeonpea wild relatives, Cajanus platycarpus, by focusing their study on flavonoid 3′5′ hydroxylase (CpF3′5′H_2), an enzyme that represents an important branch-point in the production of C. platycarpus flavonoids [H. armigera biotic stress.avonoids . By usinGlycine max) peptidase inhibitors (SPIs) in the resistance mechanisms of H. armigera larvae [H. armigera to soybean SPIs involves upregulation in the digestive system of insect genes encoding for serine peptidases. The epigenetics of SPI adaptation were studied by methylome analysis, showing that DNA methylation plays a regulatory role in insect adaptation to plant anti-herbivore defense proteins with transcriptional reprogramming that can be transmitted across generations.Marcio C. Silva-Filho and co-workers investigated the role of soybean  to detect and react to the Mexican fruit fly, Anastrepha ludens [Enrique Ibarra-Laclette and co-workers used metabolomics and transcriptomics approaches to investigate the mechanisms exploited by a ludens . TranscrPlutella xylostella is one of the most destructive pests for cruciferous vegetables, with the species having a wide distribution and the ability to adapt quickly to new environments. Shijun You and co-workers analyzed the insect trehalose transporter (PxTret1-like) and reported that the expression pattern of this gene is affected by the ambient temperature [PxTret1-like and showed that the gene regulates the main sugar—trehalose—content in the P. xylostella’s body by affecting the insect’s ability to adapt to temperature, develop, and reproduce.perature . By usinP. xylostella, increases ROS (H2O2) production and triggers calcium signaling that involves interactions with calmodulins (CAM3 and CAM7) [The emission of VOCs is one of the typical responses of plants to herbivory. By using confocal microscopy and non-invasive micro-test technology, Yingbai Shen and co-workers demonstrated that the volatile linalool, whose emission typically improves plant resistance to nd CAM7) . MoreovePsidium guajava) reduce infestation of the Asian citrus psyllid . Xinnian Zeng and co-workers report on the defense responses of sweet orange (Citrus sinensis) and show that sulfur volatiles emitted by guava play a role in plant–plant communications and trigger anti-herbivore activities against ACP [VOCs are also effective chemical signals in plant–insect interactions. Sulfur volatiles released from guava  in the recognition process of semiochemicals by cloning the cDNA sequence of EparOBP2 [E. parallelus.The rubber bark beetle EparOBP2 . FluoresWolbachia, have evolved mutualistic interactions. The fly Eurosta solidaginis induces galls in the apical meristems of Solidago altissima and hosts a strain of Wolbachia. Edward F. Connor and co-workers investigated the potential role of a bacterial symbiont in gall induction by sequencing the metagenome of E. solidaginis and its Wolbachia symbiont wEsol [wEsol genome may reveal whether genes involved in phytohormone pathways are present in wEsol and can potentially identify effector proteins secreted by wEsol. The authors showed that wEsol is absent from the salivary glands of E. solidaginis, suggesting that wEsol does not contribute to gall induction by its host.Bacteria are commonly associated with insect hosts, and some bacterial symbionts, such as nt wEsol . AnnotatThe papers published in this Special Issue provide novel insights into the complex dynamics of plant–insect interactions, shedding light on the intricate molecular mechanisms that shape their co-evolutionary relationships. This knowledge has far-reaching implications for various fields, including agriculture, ecology, and pest management.Still, several aspects of such a vital interaction between plants and insects remain to be clarified. Further exploration of the overall plant signaling pathways and their crosstalk with insect-derived molecules should be advocated. Understanding the intricacies of these signaling networks will provide valuable insights into the communication between plants and insects and may reveal potential targets for manipulation to control plant or insect resistance.The latest high-throughput sequencing and silencing technologies to study plant–insect interactions can uncover previously unknown molecular players and elucidate complex regulatory networks. Integrating genomic, transcriptomic, and proteomic approaches will provide a comprehensive understanding of the molecular basis of these interactions. In addition, the emergence of new tools such as CRISPR-Cas9 genome editing technology offers exciting opportunities for the targeted manipulation of both plants and insects.By bringing together experts from molecular biology, ecology, entomology, and agronomy, it would be possible to foster innovative research approaches that enable a holistic understanding of plant–insect interactions and pave the way for developing sustainable strategies for crop protection, ecosystem services, and environmental conservation.


Introduction: With the widespread use of wearable sensors, various methods to evaluate external physical loads using acceleration signals measured by inertial sensors in sporting activities have been proposed. Acceleration-derived external physical loads have been evaluated as a simple indicator, such as the mean or cumulative values of the target interval. However, such a conventional simplified indicator may not adequately represent the features of the external physical load in sporting activities involving various movement intensities. Therefore, we propose a method to evaluate the external physical load of tennis player based on the histogram of acceleration-derived signal obtained from wearable inertial sensors.Methods: Twenty-eight matches of 14 male collegiate players and 55 matches of 55 male middle-aged players wore sportswear-type wearable sensors during official tennis matches. The norm of the three-dimensional acceleration signal measured using the wearable sensor was smoothed, and the rest period (less than 0.3 G of at least 5 s) was excluded. Because the histogram of the processed acceleration signal showed a bimodal distribution, for example, high- and low-intensity peaks, a Gaussian mixture model was fitted to the histogram, and the model parameters were obtained to characterize the bimodal distribution of the acceleration signal for each player.Results: Among the obtained Gaussian mixture model parameters, the linear discrimination analysis revealed that the mean and standard deviation of the high-intensity side acceleration value accurately classified collegiate and middle-aged players with 93% accuracy; however, the conventional method  showed less accurate classification results (63%).Conclusion: The mean and standard deviation of the high-intensity side extracted by the Gaussian mixture modeling is found to be the effective parameter representing the external physical load of tennis players. The histogram-based feature extraction of the acceleration-derived signal that exhibit multimodal distribution may provide a novel insight into monitoring external physical load in other sporting activities. Wearable sensor devices allowing objective and real-time monitoring are becoming widespread in competitive sports . Sports Position-derived evaluation using the global positioning system (GPS) and local positioning system (LPS) have been used to assess external physical loads in various competitive sports . The traThe acceleration-derived evaluation of physical loads mitigates the disadvantage of position-derived evaluation of external physical loads . WearablIf the acceleration-derived physical load can be assumed to be normally distributed, the mean value is appropriate as a representative value. In contrast, the distribution of the acceleration-derived physical load in sports that include exercises of various intensities, ranging from walking to sprinting, remains unclear. The mean value may not adequately represent the features of the acceleration-derived external physical load assuming a simple unimodal normal distribution. Therefore, we aimed to propose a method to evaluate acceleration-derived physical loads based on the histogram of the acceleration signal obtained from wearable inertial sensors.The participants of this study were 14 male collegiate  and 55 male middle-aged players  who participated in regional qualifier rounds for national tennis championships in their categories (intercollege championship and master’s championship) . All parEach participant wore a spandex sportswear-type sensing wear (sportswear-type wearable) particularly designed for physical activity measurement . The sensing unit, comprising an inertia sensor and a data logger , was securely fixed at the upper back of the sensing wear. Before data measurement, because we confirmed that the size of the sensing wear was properly adjusted to the upper body of each participant, the acceleration data measured with the fixed inertia sensor accurately reflected the participant’s movement. In addition, the feasibility of this sensing wear to record exercise intensity has been validated . In totaThe recorded three-dimensional acceleration signal was filtered using a second-order Butterworth band-pass filter (0.5–20 Hz) to remove the high-frequency noise and baseline shift owing to the long-time recording, which also attenuated the gravity component from the acceleration signals. The cut-off frequency was determined with reference to previous studies using trunk mounted inertia sensor for evaluating locomotive motion , team sports, and contact sports . After con index  and is uon index . To idenon index  was lesson index . We assux). Because the mixing rate satisfies The histogram of the acceleration index during the in-play showed a meaningful bimodal distribution, which comprised a low-intensity peak that appeared at approximately 0.25 G and a high-intensity peak at approximately 0.9 G in the representative data . To charThe proposed and conventional methods were compared to validate the effectiveness of the proposed method. In previous studies, the norm of the raw acceleration signal was calculated, and the mean value across the target period (Eighty-three games played by collegiate and middle-aged players revealed that the acceleration index during in-play showed a bimodal distribution, which was approximated using a Gaussian mixture model comprising two normal distribution models . The intThe mean (ferences . Convers evident . The comThe Euclidean distance in the plane composed of the mean (l method . The claWe proposed a method to evaluate the external physical load based on the histogram of the acceleration index recorded by wearable sensors. The histogram of the acceleration index during the competitive tennis match showed a bimodal distribution that could be modeled using a Gaussian mixture model. The mean ( matches . Based oThe histogram of the acceleration index during the competitive tennis match showed a bimodal distribution and was adequately approximated using the bimodal Gaussian mixture model . Our preThe mean ( players . The dis σhigh , and the σhigh . We sugg players , demonst players . Using tThis study has two major limitations. First, the proposed method was only tested for competitive tennis matches. However, we believe that the proposed method to evaluate the external physical load based on the distribution of the acceleration index applies to other sporting activities during competition and training. Second, the tested dataset was only recorded from male tennis players because of the structural limitation of sensing wear. However, if a sportswear-type wearable device designed for women can record the acceleration signal using a trunk-mounted inertia sensor, the shape feature of bimodal distribution of female players would show a similar trend to male players. However, its intensity of female players is expected to be different from that of male players.We proposed a method to evaluate the external physical load based on the histogram of the acceleration index recorded by wearable sensors. The mean and standard deviation of the high-intensity side extracted by the Gaussian mixture modeling are found to be the effective parameter representing the external physical load of tennis players. The histogram-based feature extraction of the acceleration-derived signal that exhibit the multimodal distribution may provide a novel insight into monitoring external physical load in various sporting activities.


Integration of a desossiribonucleic acid (DNA) copy of the viral ribonucleic acid (RNA) into host genomes is a fundamental step in the replication cycle of all retroviruses. The highly conserved virus-encoded Integrase enzyme  catalyzes such a process by means of two consecutive reactions named 3′-processing (3-P) and strand transfer (ST). The Authors report and discuss the major discoveries and advances which mainly contributed to the development of Human Immunodeficiency Virus (HIV) -IN targeted inhibitors for therapeutic applications. All the knowledge accumulated over the years continues to serve as a valuable resource for the design and development of effective antiretroviral drugs. The International Committee on Taxonomy of Viruses (ICTV) classifies the ribonucleic acid (RNA) containing viruses into groups III-VI based on genome pairing and sign ,2,3; addAll RNA viruses rely on their own “replicase complex” to replicate, which includes highly conserved enzymes associated with ancillary structural proteins. The RNA-dependent RNA polymerase (RdRp) is the most common enzyme packed within the replicase complex, although some viral strains may also contain RNA-helicases, NTPases as well as Integrases (IN) . All sucIn this context, the viral Integrase  enzyme plays a fundamental role as it efficiently mediates the integration of the newly transcribed DNA genome into the infected host cell. In this review article, the authors report fundamental knowledge on the IN enzymes and, unless otherwise stated, specifically refer to the HIV-1 expressed isoform, which is the best characterized so far and thus generally considered as a reference among the scientific community. A selection of the main scientific contributions dealing with the IN enzyme catalytic mechanism, structural aspects, and its role in the management of viral RNA-promoted infection diseases will be discussed. The final section will be dedicated to the most innovative and promising patents covering the last 10 years.N-terminal domain (NTD), C-terminal domain (CTD), and catalytic core domain (CCD), which are schematically depicted in IN is a member of the tyrosine recombinase family, composed of the highly conserved structural domains referred to as the A representative feature of the NTD-IN is the highly conserved HHCC motif useful for binding to the viral DNA and cleaving its strands. The domain is formed by three compact α-helices stabilized through coordination with a Zn (II) ion ,14. The The CCD domain contains the IN active site with the highly conserved DDE motif, which is responsible for coordinating two Mg (II) ions  Figure . InteresThe large spatial separation between the enzyme active site, located at the CCD domain, from both the NTD and CTD sections is indicative of a high-level of multimeric organization for the entire IN enzyme . X-Ray cAmong the three IN domains, CTD is the least conserved. Nevertheless, important features such as β-folding of Src homology 3 (SH3) are highly conserved ,9. In adv-DNA)-substrate -3-hydroxy-3-propenone S-1360 (11), jointly developed by GlaxoSmithKline  and Shionogi . Compound 11 showed an IC50 in vitro value of 20 nM for the ST associated with highly effective suppression of HIV replication in in vivo infected models ..133].Either the tetracyclic and the tricyclic derivatives in 41 can be modified, as reported in 42, which maintained the same therapeutics indications and efficacy against HIV-promoted viral infections [The tricyclic compounds of general scaffold fections .43 in 44 in The spirocyclic pyridotriazines of the general structure 45 in N-indol heteroarylcarboxamide scaffold and their structural tautomers are interesting [The 5-oxopyrrolidines eresting . Such noeresting .Such compounds do act by inhibiting either the nuclear import of HIV-IN along as well as integration of HIV viral genomic DNA into the host genome .46 in Considering the variegate source of new and effective compounds offered by natural sources, we report a very interesting patent claiming compounds of macrocyclic structure After 15 years of cART, there is rising evidence of retroviruses drug resistance which poses a growing threat at a global scale. It is, therefore, imperative that new and effective strategies are needed to improve the therapeutic effectiveness of cART regimens. Such strategies include the discovery of drugs with greater efficacy and higher genetic barriers to resistance than those that are currently used, patient-centered care delivery models, and reliable drug supply chains in conjunction with frameworks for resistance monitoring and prevention . In thisv-DNA integration into the host genome by preventing the opening of the chromatin structure is targeted by the host cell’s chromatin remodeling factors [Since the very high replication cycles easily lead to resistance, continuous research efforts are needed to find alternative and efficient therapeutic approaches for the management of retrovirus infections. Experimental approaches of relevance, although still in early stages, include: (i) inhibition of viral DNA integration into the host genome is accomplished by preventing PIC transport into the nucleus. This is put into practice by integrase-mediated nuclear import inhibitors, which bind to the host cell’s nuclear import protein ; (ii) IN factors .The development INSTIs for experimental uses and the introduction into the cART of appropriate derivatives represented a major advancement in the field of retroviruses. These drugs specifically target the viral IN enzyme, which is responsible for integrating the viral DNA into the host cell’s genome during the replication process. INSTIs demonstrated high potency in suppressing viral replication and reducing HIV viral load in infected individuals. In addition, when INSTIs are used in combination with other antiretroviral drugs , they can effectively control the viral load, allowing patients to lead longer and healthier lives. Compared to some older classes of antiretroviral drugs, INSTIs showed a lower propensity for the development of drug resistance and thus remained effective for a more extended period, reducing the risk of treatment failures. Some INSTIs are available as once-daily dosing, making them more convenient for patients and improving treatment adherence. In addition, INSTIs are often recommended as part of the first-line treatment for HIV-affected patients. Recently have also been used to prevent mother-to-child transmission of HIV during pregnancy and childbirth. Administering these drugs to the mother and newborn resulted in a significant reduction of the risks associated with vertical transmission of the virus.


Much progress has been achieved in the understanding of the effect of food and nutrients on preventing non-communicable chronic diseases . DietaryEstimating the dietary impact and health benefits of front-of-pack labeling regulations in Canadian adults” and “The estimated dietary and health impact of implementing the recently approved ‘high in' front-of-package nutrition symbol in Canada: a food substitution scenario modeling study” examines the potential impact of recently introduced dietary regulations on promoting healthy diets and reducing deaths in the Canadian population . Using different contrafactual scenarios, both studies show that Front-of-Pack Labeling (FOLP), by significantly reducing sodium, total sugar, and saturated fat intakes among Canadians, has the potential to prevent or postpone ~70% of diet-related NCD deaths in the country. This studies' findings provide critical evidence for policymakers and health authorities from all over the world considering the potential implementation of FOPL regulations.The papers, titled “Health economic impacts associated with the consumption of sugar-sweetened beverages in Brazil” and “Chronic diseases attributable to a diet rich in processed meat in Brazil: burden and financial impact on the healthcare system” were based on ecological studies using data the Global Burden of Disease (GBD) to estimate the direct economic costs and the burden of non-communicable diseases associated with selected dietary risk factors in Brazil . Both studies demonstrated the relevant health and epidemiological impact of these dietary risk factors among Brazilian adults. In addition, it brings interesting methodological alternatives for modeling country data such as using the GBD estimates at the country and subnational levels. Their results represent relevant subsidies for evidence-based policies to tackle NCDs.Two other papers from this supplement, entitled “Bi-objective goal programming for balancing costs vs. nutritional adequacy” to deal with optimum lowest-cost and highest-quality diet planning . In their work, they present a method to find all trade-offs between any two linear objectives in a dietary linear programming context focusing on the trade-off between the costs of a diet and its nutritional adequacy. This method helps not only practitioners to understand better the possibilities for a diet that is as nutritious as possible within budgetary restrictions but the design of low-cost dietary interventions.An innovative approach was introduced in the paper “Economic and health impacts of the Change4Life Food Scanner app: findings from a randomized pilot and feasibility study” developed a pilot randomized controlled trial for evaluating clinical outcomes in children and economic effectiveness of the UK's Food4Life Food Scanner app, which is aimed at providing the nutritional content of packaged foods to families in order to encourage healthier diets among children . Although modest mean differences between study arms were found over a short follow-up period, the study brought lessons on the feasibility of the strategy, yet it faces difficulties in obtaining data on app costs, and highlighted the importance of long-term economic modeling compared to short-term outcomes that may not be captured.Finally, the paper “In summary, different methodologies for modeling the health and economic impact of risk factors and interventions can contribute to producing evidence for decision-makers in order to support more effective and cost-effective health policies in different countries that face common challenges in controlling and preventing diet-related diseases.EV: Conceptualization, Writing—original draft. IM: Conceptualization, Writing—original draft. EN: Conceptualization, Writing—original draft.


Hearing loss is the most common human sensory deficit. Severe-to-complete sensorineural hearing loss is often treated by electrical cochlear implants (eCIs) bypassing dysfunctional or lost hair cells by direct stimulation of the auditory nerve. The wide current spread from each intracochlear electrode array contact activates large sets of tonotopically organized neurons limiting spectral selectivity of sound coding. Despite many efforts, an increase in the number of independent eCI stimulation channels seems impossible to achieve. Light, which can be better confined in space than electric current may help optical cochlear implants (oCIs) to overcome eCI shortcomings. In this review, we present the current state of the optogenetic sound encoding. We highlight optical sound coding strategy development capitalizing on the optical stimulation that requires fine-grained, fast, and power-efficient real-time sound processing controlling dozens of microscale optical emitters as an emerging research area.  Neuroscience; Bioengineering Most currently used sound coding strategies for eCIs are based on filter-bank processing and interleaved stimulation at a constant stimulation rate B. In genn-of-m type strategies were developed .,,,,,,,,,The continuous interleaved sampling (CIS),Efforts to improve speech recognition include model-based coding strategies, which started with auditory-model-based ACE versions (EZ-ACE and IHC-ACE).,Thanks to the development in the miniaturized light-emitting, -focusing, and -delivering components, oCIs can be implemented with either an array of intracochlear optoelectronic emitters  is another emitter candidate for the active oCI implementation. Integration of OLEDs on top of the complementary metal oxide–semiconductor substrates (OLED-on-CMOS technology)Finally, microscale lasers such as vertical-cavity surface-emitting lasers (VCSELs) have been employed for active oCIAlthough the active oCI implementation is currently the most technologically ready, passive oCIs represent an attractive option with a favorable safety and stability profile. In this design, all electrically active components are hermetically enclosed in the titanium housing of the implant in analogy to the current sources in eCI systems,,,Light delivered from optical fibers chronically implanted into the round window for single-channel stimulation of the cochlea drove a behavioral response in awake gerbils and proved an auditory percept due to optogenetic stimulation.n channels for broadening neural excitation at a specific tonotopic position for encoding loud sounds.Just like for eCI, the oCI hardware design determines the features available for coding strategy. Considerations for oCI design include single vs. multiple wavelength(s), e.g., for diversified excitation or combined excitation and inhibition, as well as number, type and operation of emitters and their addressing. The latter is relevant for independent operation of channels as required for parallel stimulation of multiple sites. Power consumption is another important consideration as current estimates of required pulse energy of oCI exceed that of eCI (see below). Hence, maximizing efficiency of emitter operation such as driving laser diodes with large current but ultrashort pulses that are then integrated by optogenetically modified SGNs is important and will also serve the oCI heat management. Efficient integration of injected currents by SGNs has been demonstrated for direct current injection,,,,Future oCIs directly trigger firing of SGNs that express channelrhodopsins , i.e., bypassing dysfunctional or lost IHCs. Wavelength, kinetics, and energetics of optogenetic stimulation need to be tuned to the action spectrum, light sensitivity, conductance, and gating kinetics of the ChR employed. To a first approximation the temporal fidelity of optogenetic SGN stimulation is limited by deactivation time constants of the channelrhodopsins. For example, the blue-light-activated ChR2,,Ultrafast red-light-activated ChRs such as f-Chrimson and vf-Chrimson seem to be good candidates for clinical translation given suitable kinetics and the lower risk for phototoxicity for the lower energy photons. As the energy requirement of optogenetic stimulation is another important consideration and more favorable for f-Chrimson than for vf-Chrimson, f-Chrimson might be the better choice as it lends to comparable temporal fidelity of SGN firing.,,,,,,,,,Current preclinical work often involves early postnatal intracochlear injection of adeno-associated virus (AAV) which routinely achieves transduction of ≥70% of the SGNs,Optical sound coding strategies need to consider several constraints such as limited temporal fidelity of coding reflecting ChR kinetics, increased number of stimulation channels relative to electrical CI system, requirements for the power-efficient operation of optical emitters, maximal current consumption, and battery lifetime. The minimal duration and intensity of a light pulse sufficient for optogenetic SGN activation depends on the level of ChR expression (see above), the single channel conductance of the ChR, as well as on the ChR’s closing kinetics. Taking advantage of the expected greater frequency selectivity of the oCI, parallel stimulation by a number of emitters selected from 50 to ≥100 emitters, could be considered, which seems feasible given the current technology. Recruitment of neighboring emitters for increasing the population of activated SGNs at a given tonotopic position will likely help mimic physiological loudness coding that relies on increasing the number of activated SGNs and their firing rate.,To evaluate advantages of parallel stimulation over interleaved stimulation, we employed custom scripts in MATLAB R2016a (The MathWorks Inc.) to generate electrodograms or “emittograms” for a ten-channel implant, state-of-the-art eCI or e.g., LED-based active oCI used in proof-of-concept studies of oCI systemin silico evaluation approaches will be beneficial for the future development of the entire system and smooth translation into clinical trials. They ideally complement animal experiments and help to focus these studies, thereby reducing the number of animals required for preclinical evidence. Existing speech intelligibility metrics could be used for analysis of in silico results . The evaluation was implemented in MATLAB R2016a (The MathWorks Inc.) and used publicly available code of Analysis & Resynthesis Sound Spectrograph (ARSS)While several studies support that the hearing performance of eCI users improves with increasing number of spectral channels,,,Recently, the combined use of electrical and optogenetic stimulation was studied.,,Pioneering work of Djourno and Eyriès in France inspired House and Doyle in Los Angeles, and just 4 years later, in 1961, two human patients were implanted with the first prototype of a “real” eCI.,However, as the number of physical channels in eCI, as well as speech recognition in quiet reached steady state for over a decade,,The main objective of oCI development is an increased number of non-overlapping stimulation channels inside the cochlea to enable higher spectral resolution than in eCI. Technological feasibility is suggested for active oCIs that could integrate 144 μLEDs on 12 mm . The insertion of active oCIs into explanted mouse cochlea—5-fold smaller than human cochlea—with 93 μLEDs inside Scala tympani covering a tonotopic frequency range of 72.2 kHz (base) to 2.5 kHz (apex) was reported.,,Due to the trade-off between ChR open time and energy requirements, sound coding strategies of the first generation oCIs will likely operate at lower stimulation rates than eCIs. This could compromise the temporal fidelity of sound encoding such as for sound localization, which however, is limited also for eCI . With a vector strength of 0.5 for stimulation rate of ≥200 Hz we would expect the temporal precision of oCI coding to enable temporal fine structure coding, which has been implemented for low frequency eCI channels with subtle improvements in speech understanding.,In order to meet current standards, oCIs will need to function for many years without failure ideally covering lifespan of patient. In reality, the survival rate of eCIs strongly depends on device and patient age and reaches up to 30 years in a 30-year analysis window with MED-EL devices reaching 10-year cumulative survival rate of 99% in adults and 97% in children.Longevity of the entire concept of optogenetic hearing restoration also depends on stable expression of ChRs. Unleashing the full potential of optogenetic hearing restoration will be best served with a rich complement of light-sensitive auditory nerve fibers.in silico study of intracochlear light propagation.,,,,Another critical point concerning oCI function is the orientation of emitters for optimal optical stimulation. Irradiance at the level of the SGN somata in Rosenthal’s canal was recently investigated as a function of emitter distance and orientation in an ,Considering energy consumption, a custom-built preclinical CI system managed to achieve similar time of operation of single-channel stimulation with eCI and oCI based on μLEDs  using general purpose commercial out of shelf components.


A large and consistent literature converges in pointing out how hippocampus-dependent memories benefit from slow wave activity during non-rapid eye movement sleep (NREM). The declarative memory traces are repeatedly reactivated during slow-wave sleep (SWS), promoting long-term storage at the cortical level , 2. SleeAnother gap in the literature addressing the relationship between REM sleep and memory function is represented by the common practice of considering paradoxical sleep as a homogeneous state, especially in human studies . HoweverSLEEP, van den Berg and collaborators [n = 20 per group) performed the Tower of Hanoi task before and after (1) an undisturbed 8-hour period of sleep, or (2) a same-length wake period. Each group also took part in another similar condition  in which a non-learning control task was performed. The study [In the August issue of borators  addressehe study  adopted he study  classifiBesides confirming the beneficial effect of sleep on problem-solving performance , 4, the Overall, the presence of post-learning variations in the EEG activity time-locked to EMs during REM sleep indicates an engagement of the cortical processes that occur during EMs in the procedural memory consolidation. This evidence involves both phasic and tonic REM periods, albeit only those changes that occurred during phasic REM periods were predictive of the improvement in cognitive performance, suggesting a different functional role of the two substates in the sleep-dependent consolidation processes.sensorimotor rhythms (SMR), although others have defined the same activity as Mu [theta rhythm, thus including low frequencies (2–4 Hz) belonging to the delta band. Following this choice, the discussion of the findings involving the < 8 Hz activity has been mainly focused on the available evidence linking REM theta oscillations to memory consolidation, although in most human studies a standard 5–8 Hz definition of the theta band has been adopted. From a different perspective, it could be interesting to provide an alternative interpretation of the post-learning increase in the 2–4 Hz activity found in the prefrontal region. We might look at these results in light of the possible implication of the 2–4 Hz EEG rhythms during phasic REM sleep in memory consolidation. Recent studies indeed demonstrated the existence of slow oscillations in this frequency range during paradoxical human sleep, and defined them as sawtooth delta waves [In discussing the results, the authors  interprety as Mu . Moreoveta waves , 17. Theta waves . In thisIn conclusion, this study provides tantalizing clues about the role of paradoxical sleep EMs and their concomitant neocortical activations in the consolidation of problem-solving skills.The application of the ERSP approach to sleep EMs paves the way for future investigation to explore the involvement of EMs and their correlates in several sleep-dependent cognitive domains, disentangling the differential contributions of tonic versus phasic REM states not only in memory consolidation, but also in dreaming or REM-related sleep disorders.The present study raises as many questions as it answers, highlighting the need for future research. What drives the differential involvement of delta, theta, and SMR activity during phasic and tonic REM sleep? Can these findings be generalized to other types of procedural learning? What are the implications for sleep disorders or conditions characterized by REM sleep alteration, such as in aging , post-tr


Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention. We present ModelAngelo, a machine-learning approach for automated atomic model building in cryo-EM maps. By combining information from the cryo-EM map with information from protein sequence and structure in a single graph neural network, ModelAngelo builds atomic models for proteins that are of similar quality as those generated by human experts. For nucleotides, ModelAngelo builds backbones with similar accuracy as humans. By using its predicted amino acid probabilities for each residue in hidden Markov model sequence searches, ModelAngelo outperforms human experts in the identification of proteins with unknown sequences. ModelAngelo will thus remove bottlenecks and increase objectivity in cryo-EM structure determination. Knowledge of the three-dimensional atomic structures of proteins and nucleic acids is pivotal for our understanding of the molecular processes of life. In recent years, considerable advances have been made in the determination of structures of biological macromolecules by electron cryo-microscopy (cryo-EM), culminating in cryo-EM maps of proteins with sufficient resolution to resolve individual atoms ,2. AccorOver two-thirds of last year’s (2022) structures had resolutions better than 4 Å. Although individual atoms are not resolved at resolutions between 2-4 Å, reliable atomic models can be built by exploiting prior knowledge of the chemical structures of the proteins and nucleic acids in the sample, including their amino acid and nucleic acid sequences. Typically, atomic model building in cryo-EM maps is performed using manual procedures in three-dimensional computer graphics programs , 6. AtomStructure determination by cryo-EM is also an increasingly important tool for the discovery of new subunits in biological complexes. Because of its relaxed requirements for sample quantity and purity compared to other structural biology techniques, cryo-EM is capable of determining structures of complexes purified from endogenous sources. Many such complexes contain subunits of unknown identities. Without prior knowledge of the amino acid sequence, identifying the chemical identity of individual amino acids in cryo-EM maps is difficult, and requires relatively high resolutions. Yet, provided one can build stretches of several consecutive amino acids, database searches with the sequence fragments can lead to the identification of the corresponding protein. Recent examples include the identification of TMEM106B in amyloid filaments from human brains -11 and tHere, we introduce a machine-learning approach, called ModelAngelo, for the automated building of atomic models and the identification of proteins in cryo-EM maps. Machine learning approaches often require large amounts of training data. For example, recent protein language models were trained on tens of millions of sequences  and AlphThe sudden availability of atomic models for millions of proteins from protein structure prediction by AlphaFold2 , 16 has Automated model building of proteins and nucleic acids in ModelAngelo comprises three steps . Detailsα atom of amino acids and the phosphor atom of nucleic acids are predicted using a convolutional neural network (CNN). This CNN is a modified feature-pyramid network  is used to optimise the positions and orientations of the residues, to predict their amino or nucleic acid identity, and to predict torsion angles for their side chains or bases. The GNN consists of three modules: a cryo-EM module, a sequence module, and an invariant point attention (IPA) module . Each noThe cryo-EM module incorporates information from the cryo-EM map and comprises two parts. Firstly, the input feature vector is passed through a multi-layer perceptron (MLP) network to generate query and value vectors. These vectors are used for cross-attention  with keyThe sequence module performs cross-attention for each residue with the user-provided amino acid sequences, which are embedded using the pre-trained protein language model, ESM-1b . This inThe IPA module incorporates information from the geometry of the nodes in the graph and was inspired by the module with the same name in AlphaFold2 . An MLP The residue feature vectors are post-processed to generate an atomic model. The feature vectors are used as inputs into two separate MLPs to predict new positions and orientations for each residue, as well as torsion angles for amino acid side chains and nucleic acid bases. They are also used to predict a confidence score for each residue, which is based on the network’s predicted root-mean-square deviation (RMSD) for the backbone atoms with the deposited structure. In addition, the predictions for the amino or nucleic acid identities from the cryo-EM and sequence modules are averaged to generate probabilities for each possible identity for all residues. These vectors are converted into a hidden Markov model (HMM) profile (see below) that is used for a search against the input sequences using HMMER . MatchedFinally, chains shorter than four residues are pruned from the model, and a full atomic model is generated from the predicted positions and orientations of each residue and their corresponding amino acid or nucleic base torsion angle predictions, using idealised geometries. The predicted backbone RMSD values are mapped to a score between 0 and 1, corresponding to a linear range for RMSDs between 1.2 and 0.5 Å, respectively. This score is stored in the B-factor column of the output coordinate file as a measure of local confidence in the backbone geometry.A profile HMM is a probabilistic model representing the multiple sequence alignment (MSA) of a set of related sequences. The parameters of a profile HMM are normally estimated from the MSA it strives to model, however, here, they are instead estimated from ModelAngelo predictions. There are three types of states in the profile HMM. For each position of the MSA’s consensus sequence, there is a match  took 2 minutes; the largest structure  took 53 minutes. The output coordinates from ModelAngelo were refined against the cryo-EM map using a standard refinement cycle in Servalcat , and theα atom within 3 Å of the deposited model and with the correct amino acid assignment. As with backbone RMSD, completeness improves for residues with higher Q-scores . . Scytonehofmanni , we obsehofmanni . Users shofmanni -49. Nonehofmanni  and Cryohofmanni . ModelAnhofmanni .in situ in the red alga Porphyridium purpureum , photosystem I and II (PSI and PSII), and the transmembrane light-harvesting complexes (LHCs) that was imaged urpureum . The secom cilia ,13.PP1 (linker of PBS–PSII 1); CNT (for “connector”); PsbW and Psb34 (two of the core subunits of PSII); LRH (a linker protein); and LPS1 (photosystem linker protein 1). To identify these chains, we ran ModelAngelo without using its sequence module (using the build_no_seq option) to calculate an initial atomic model with HMM profiles for all chains, and we searched these profiles against the proteome constructed in (hmm_search option). Because of local pseudo-symmetry, all six unidentified proteins occur more than once in the cryo-EM map. This allows us to bootstrap weaker individual hits by cross-referencing their matches to the other instances. Specifically, the same six protein chains were identified for all instances, with E-values in the range of 5.8e-66 to 6.4e-2. Using the backbone traces in the deposited model, findMySequence  consists of 158,730 residues in 81 unique protein chains, including six chains for which the authors were unable to identify the corresponding protein. The unidentified chains were termed Lucted in   and 48 different CA proteins  was identified from a fragment of just 33 residues, demonstrating the power of ModelAngelo to identify proteins from small sections of well-resolved density. Both CA proteins (FAP92 and FAP374) bind directly to the microtubule surface and have tertiary structures poorly predicted by AlphaFold2  and radial spoke complexes isolated from proteins , 13, theproteome  (Figure proteome . Using Mproteome  was unabphaFold2 ; sidechaphaFold2 . The ideModelAngelo automates atomic modelling in cryo-EM maps, building protein models of comparable quality to those built by human experts and nucleic acid models with near-complete and accurate backbones. ModelAngelo outperforms existing approaches for the automated modelling of both proteins and nucleotides. Furthermore, ModelAngelo builds these models within hours on a modern GPU, thereby removing an important bottleneck in cryo-EM structure determination. Future incorporation of ModelAngelo into automated cryo-EM image processing pipelines -61, willBy introducing objectivity in the model-building process, ModelAngelo also informs which parts of the map can be confidently interpreted with an atomic model and which should be left uninterpreted. In this way, ModelAngelo will not only reduce the number of errors in atomic models but also play a role in making cryo-EM structure determination more accessible to the large numbers of newcomers that the field has experienced in recent years. Still, some degree of human supervision and intervention will remain necessary. Models from ModelAngelo will still need refinement, for example in Servalcat  or PheniBesides accelerating cryo-EM structure determination and providing objectivity in atomic modelling, ModelAngelo also identifies protein chains in cryo-EM maps better than human experts. The reason why ModelAngelo outperforms the human expert in this task likely lies in the implementation of its sequence searches. While human experts typically base their identifications on discrete assignments of individual amino acids to various residues in unknown chains, ModelAngelo exploits predicted probabilities for all twenty amino acids for every protein residue and combines this information with its predicted confidence in each residue in a full HMM search. This not only allows better identification of unknown chains but also helps ModelAngelo during the building of atomic models with known sequences, where it may potentially outperform human experts in placing protein chains for which ambiguity exists, for example when multiple homologous chains coexist in a single structure. The ability to identify proteins in cryo-EM maps will increase in importance as ongoing advances in sample preparation, microscopy, and image processing allow ever more structures to be determined for samples purified from native sources or visualised in situ by electron tomography of frozen cells or thin tissue sections.


The Agrobacterium-Mediated Transformation has been used for genetic engineering of Tree Fruit Crops for more than three decades. Much progress has been made in this field  although many obstacles remain for utilization of this technology at levels used for herbaceous and annual plants. In the second volume of this Research Topic, there are papers describing approaches different research groups are taking to facilitate genetic transformation of recalcitrant tree species and on a more basic level understand mechanisms of insertion of T-DNA into the genome of host cells.Gelvin et al. investigated formation of T-circles as a proxy for understanding T-DNA integration. In this work, regions associated with the LB-RB junction were characterized in detail from T-circles formed in transgenic plants of Nicotiana benthamiana or Arabidopsis thaliana. It was shown that RB-LB junctions in T-circles were similar to junctions between T-DNA and the plant DNA where integration took place. Similarities included: higher frequency of deletions and more extensive changes in sequence at the LB in comparison to RB; presence of microhomology at junction sites; presence of filler DNA originating from Agrobacterium or plant genome; concatemeric organization of multiple copies of T-DNA with RB-RB and LB-LB junctions being more frequent than RB-LB junctions. Furthermore, the authors have shown that T-circles formation proceeded without Ku80 and ω mutation in VirD2 gene of Agrobacterium had an effect similar to the effect exerted on T-DNA integration. Based on their data the authors suggested that formation of T-circles can be used to study all aspects of T-DNA integration into host’s genome.In an elegant study Dominguez et al.) developed a method that should facilitate transformation of 14 citrus cultivars. They have achieved this by addition of supplements such as spermidine, and lipoic acid to media used in transformation protocol and by using a helper plasmid pCH32 containing additional copies of VirG and VirE genes. Presumed role of the supplements was to lessen the oxidative stress in explants incubated with Agrobacterium whereas VirG and VirE genes were supposed to enhance integration of T-DNA. Transformation efficiency for some cultivars was increased to 11% (as percentage of GUS-positive shoots produced per number of explants used in the experiment) and the period for production of soil-acclimated transgenic plants was shortened to six months for some cultivars. Based on Southern blot analyses, the number of integrated T-DNA copies ranged from one to four. This method has a potential to help researchers using Agrobacterium-mediated transformation achieve higher productivity.Most of the work published on citrus transformation, utilized material from only a few cultivars that were relatively easy to transform . Mandadi’s group at TAMU  summarize the progress in application of transgenic technology to apples and offer possible directions for the future research. The non-browning Arctic® apples remain a single achievement of research in apples where final product found its way to the market. However, in recent years use of various starting materials and media for transformation, refinement of agroinfiltration conditions, as well as pre-transformation with a BABY BOOM transcription factor led to improved transformation efficiency in apple. New strategies for gene silencing have also been used for apples. Those include RNAi-based silencing by stable transformation with hairpin gene constructs, virus-induced gene silencing (VIGS) and artificial micro RNAs (amiRNAs). The targeted genome editing (GE) in apples resulted in production of a homohistont GE line into which a biallelic mutation was specifically inserted in a target gene. Finally, this review discusses methods in which genetically modified plants are used for the rapid crop cycle breeding system.Researchers working with apples face similar challenges as those working on citrus transformation include low efficiency. In the review paper (Pyrus pyrifolia Nakai.) is regulated by complex interaction of multiple transcriptional regulators where BBX (B-box) plays the important role. However, the upstream regulation of BBX genes has not been well characterized. It was known from recent work that PpBBX18 interacts with PpHY5 via two B-box domains and then forms a heterodimer. The PpHY5 binds to the G-box motif of PpMYB10 and PpBBX18 provides the trans-acting activity, thus inducing transcription of PpMYB10 as well as anthocyanin biosynthesis . In the work by Zhang et al. PpZAT5, a cysteine2/histidine2-type transcription factor, was discovered as the upstream negative regulator of PpBBX18. PpZAT5 expression was inhibited by light, which is converse to the expression pattern of anthocyanin-related structural genes. The results of this study showed that PpZAT5 functions as a transcriptional repressor which can directly bind to the CAAT motif of PpBBX18 and inhibit its expression thereby inhibiting anthocyanin biosynthesis.Anthocyanin biosynthesis in the peal of red pear (Capriotti et al. have combined somatic embryogenesis and organogenesis to facilitate transformation of the Vitis vinifera cultivars Ancellotta and Lambrusco Salamino, in comparison with the model cultivar Thompson Seedless. Plantlets obtained through from somatic embryogenesis from flowers were used as starting materials to obtain explants for transformation experiments. Cotyledons and hypocotyls were incubated on media with different combination of growth regulators to estimate their competence for shoot organogenesis. While explants from both Ancellotta and Lambrusco Salamino produced high number of GFP-expressing calli, this approach has produced only one transgenic plant of the Ancelloto cultivar. Definition of novel protocols combining in vitro regeneration and genetic transformation of grapevine including the wine grape and table grape varieties will be essential for the application of emerging methods aimed at improvement of agronomic and commercial traits.Genetic transformation of grapevine cultivars can be considered extremely difficult. VO wrote the Editorial. HP read and approved the text.


To compare and assess the enamel surface roughness by Atomic Force Microscopy between ceramic and metal brackets after adhesive removal with 3 different methods.  90 extracted premolars were collected and divided equally into 3 groups G, Y, and R. With group G bonded with metallic brackets (using primer and Transbond XT), group Y with ceramic brackets (primer and Transbond XT), and group R with ceramic brackets (silane and Transbond XT). Each group was subdivided into 3 sub-groups (10 premolars each) based on the resin removal method as A: 12- flute tungsten carbide (TC) bur (high speed), B: 12- flute TC bur (low speed), and C: 30 flute TC bur (low speed). Surface roughness values were calculated and compared before bonding and also after adhesive removal by atomic force microscope (AFM). Measured data were analyzed using paired student t-test, ANOVA, and Tukey’s tests. P<0.047). Whereas, within the subgroups, subgroup A  with Rq showed increased surface roughness which was found to be statistically significant (P<0.042).Among the groups, group G showed increased surface roughness after debonding compared to group Y and group R, with Rq value showing a statistically significant difference ( None of the adhesive removal methods was capable to restore the enamel to its earlier morphology; a statistically significant increase in surface roughness parameters was reported with a high-speed 12 flute TC bur for Rq and Rt. Due to the increase in demand for orthodontic care, orthodontists preferred to provide their patients with better and aesthetically pleasing appliances and bonding techniques. The bonding technique was developed not only to reduce the metallic appearance of bands but also as an initiation to improvise the acceptance and aesthetic appearance of the orthodontic appliance. the only disadvantage of this technique is that it can lead to irreversible alterations on the enamel surface.Although there are many advantages of the direct bonding technique in orthodontic therapy, like maintenance of healthy gingiva, better patient compliance and enhanced clinical effectiveness, Gross enamel damage was manifested after debonding with a few of the initial generations of ceramic brackets; the bonding strengths acquired with ceramic brackets are of chemical-mediated adhesion. A silane coupling agent containing a bi-functional molecule with a reactive silanol group at one end that binds firmly to glass and another molecule reacts with adhesive resins and undergoes polymerization, forming a cohesive bond with the adhesive material.As more adults started taking orthodontic therapy, this promoted the development of ceramic brackets. Ceramic bracket undergoes bond fracture primarily at the adhesive-enamel interface whereas in metallic brackets bond failures occur frequently at the adhesive-bracket interface. The bond strength of ceramic and adhesive is stronger than the bond strength of the adhesive and the enamel. During de-bonding, bracket failure, particularly with the ceramic bracket, occurs in adhesive failure ie.; at the resin and enamel but enamel fracture can also occur with metal bracket.With the advancement and improvement in newer generations of ceramic brackets, the possibility of enamel alterations is reduced. Although quantitative evidence to prove such a claim is very less. Incomplete removal of these resin leftovers can lead to unesthetic discoloured surfaces on tooth and plaque accumulation due to irregular finished surfaces, ultimately leading to enamel demineralization.With contemporary advancements in bonding materials , after debonding, the clean-up of residual resin has become a clinical challenge especially in maintaining the enamel integrity.However, there is no universally approved protocol in the previous studies regarding this issue although routinely practised methods of residual adhesive removal from surface of enamel is by utilizing low-speed tungsten carbide (TC) bur accompanied by an appropriate polishing disc and subsequent polishing paste. Atomic force microscope (AFM) assessment is one of the methods that utilize numerous scans at a high level of resolution and is proposed for surface analysis with irregularities at a nanoscale. Such quantitative assessment helps in a better comparative assessment of enamel destruction resulting from different debonding and composite clean-up methods. Furthermore, it has a lot of other advantages over other methods, for example, minimum specimen preparation, simultaneous 2Dimensional and 3Dimensional imaging and probability of re-examining the samples.Assessment of enamel surfaces following residual resin clean-up with different rotary instruments evaluated by scanning electron microscope (SEM) and other optical imaging scanners have proven to be unreliable and subjective and do not render the exact quantitative results. Hence this research aimed to compare and assessment of enamel surfaces subjected to various bonding  and resin removal methods after debonding using an AFM.Ninety extracted premolars (orthodontic purpose) were collected from patients in an age range of 15-20 years and preserved at room temperature in the water till they were prepared and analyzed. The selected teeth were intact with no caries or restorations, teeth with no hypo-calcifications or fluorosis and teeth with no visual cracks. The specimen teeth were embedded in custom-made blocks of acrylic resin and stored in 0.9% normal saline solution, later which were randomly categorized into three different groups based on colour codes as   to anticGroup G = includes 30 premolars with metallic brackets (3M Unitek) bonded using primer and Transbond XT adhesive. Group Y = includes 30 premolars with ceramic brackets (3M Unitek) bonded using primer and Transbond XT adhesive. Group R = includes 30 premolars with ceramic brackets (3M Unitek) bonded using silane coupling agent and Transbond XT adhesive. All samples  were evaluated with the AFM before bonding for initial measurements . The AFM These measurements include roughness parameters given in nanometres:Ra value: Mean roughness values are the arithmetic average deviation of the surface heights (peaks) and depth  from a centre line of the assessment length Rq value: Root mean square roughness is the height deviation parallel to the centre line of assessment length Rt value: Maximum roughness height that designates the maximum profile on the surfaces . After mounting, the samples were cleansed with water followed by drying with pressurised air (oil-free). All the samples were etched with 37% ortho-phosphoric acid for 30 seconds, washed and air dried, till a frosty dull white appearance is observed on the etched surface. In groups G and Y, the adhesive primer was coated on the teeth and cured with LED light for 10 seconds, then both were bonded using Transbond XT orthodontic adhesive and in group R, a silane coupling agent along with the same adhesive was used. The brackets were seated in the centre of the tooth with firm pressure. With the help of the sharp explorer, excess flash is removed carefully and cured for 40 seconds as per the manufacturer’s instruction. Then cured specimens were preserved in isotonic saline solution for 7 days at room temperature before debonding. Debonding of the bracket was carried out by debonding pliers with the application of gentle compressing force on the tie wings. The resin leftovers are removed by three different methods, which were as follows:Sub-group A: Clean-up with high-speed 12-flute TC bur (10 teeth surfaces per group) Sub-group B: Clean-up with low speed 12- flute TC bur (10 teeth surfaces per group) Sub-group C: Clean-up with low speed 30 flute TC bur (10 teeth surfaces per group) After the full removal of the adhesive remnants from the teeth surfaces, the teeth were examined visually under operating light in both wet and dry environments, After that, all the specimens were once again assessed by AFM to determine different parameters of enamel surface roughness i.e. Ra, Rq and Rt. . All theP < 0.05 was determined for all analyses.The surface roughness values of enamel were tabulated and analysed with SPSS version 23 . The normality assumption of distributed variables was tested by the Shapiro-Wilk test. Roughness parameters  were assessed before bonding and after residual resin, removal using the paired student t-test. Roughness parameters for each group were analysed using ANOVA and for multiple comparisons within the groups, the Tukey test was used. The level of significance of P < 0.001) as shown in Comparing the initial values with values after all the 3 resin removal methods, showed an increase in enamel surface roughness. The roughness parameters  values in all the 3 groups showed statistically significant changes after enamel clean-up compared with the baseline values , and according to Tukey’s post hoc tests, Rq values are highly significant for group G between sub-group A and B (P = 0.042) i.e. between high speed 12- flute TC bur and low speed 12- TC bur  and statistically significant differences for Group Y (P = 0.024). Multiple comparisons of Rt values for Group G showed highly significant differences between Sub-groups A and B (P = 0.006) and significant differences between Sub-groups B and C (P = 0.049) i.e. between high speed 12-flute TC bur and low-speed 12-flute TC bur and between low-speed 12-flute TC bur and low-speed 30-flute TC bur respectively. Multiple comparisons of Rt values for Group Y showed a significant difference between Sub-groups A and B (P = 0.018) i.e. between high-speed 12-flute TC bur and low-speed 12-flute TC bur  bonded by different techniques and also the effect of three composite removable procedures on enamel surface roughness.Recent advancements in dental materials resulted in superior bond strength between enamel and adhesive, minimizing bracket bond failure rate. Debonding and adhesive removal procedures are dependent on operated, so the results might differ among operators. To minimize the error, a single operator performed all the clinical procedures.In this experimental study, the assessment of surface roughness was subjected to AFM as it is a non-invasive approach and has proven to be an effective analysis for hard surfaces like enamel that illustrates micro-irregularities. Furthermore, AFM gives 3D data at the nanoscale level with perpendicular and asymmetrical resolutions, requiring minimum specimen preparation and also helps to re-examine the sample again. This cannot be utilized for comparative and correlative assessment of surface roughness between the groups. Thus, this study has an advantage as quantitative measurements from AFM help in better comparative assessment between groups.Previous studies have used SEM images to assess surface roughness; although, this method can provide only qualitative data i.e.; subjective information. Sigilião et al stated that all rotary instruments lead to alternation in enamel morphology.From the results, it was found that irrespective of the adhesive removal methods used (bur type), an increase in surface roughness values of enamel was observed after resin removal therefore none of the adhesive removal methods can fully restore the enamel to its earlier morphology as found in previous studies. TC burs have different shapes and various blade types. The regularly operated TC burs have 8-30 flutes. 12-30 flute TC burs were considered to cause less damage to enamel. Thus 12 and 30 flute TC burs were evaluated in this experimental study.TC burs are the most commonly used adhesive removal burs by clinicians. The findings were in agreement with those of Ahrari et al and Hannah and Smith. They have highlighted that low-speed TC burs would be less deleterious to the adjacent enamel compared to high-speed TC burs for resin removal.In this study after the residual resin removal between 12 flute TC bur at high-speed and 12 flute TC bur at low-speed it was observed, an increase in surface irregularities on the enamel surface which were significant for Rq group G,  and Rt  but not  which follows our study.Previous studies recommend the usage of low-speed 12-flute TC burs, which generate minute scratches with a lesser level of enamel loss who suggested that 30 flutes TC bur was the most efficient procedure of highly filled resin removal with less quantity of enamel scar, this concordance in the study might be due to the variation in resin removal methods and the type of investigation carried out as earlier was an SEM study.Multiple comparisons of Rq and Rt values in metal brackets with mechanical retention showed more enamel surface irregularities with high-speed 12 flute TC but when compared with low-speed 12 flute TC bur. Similar findings were observed in the ceramic bracket with mechanical retention for Rt. Rt values in the ceramic bracket with chemical retention showed more enamel surface roughness with low-speed 30 flute TC bur when compared with low-speed 12 flute TC bur. This study is not in agreement with Campbell et al reported that there was an increase in surface roughness parameters at Ra and Rz along Y-axis with 5-blade TC bur compared to the 30-blade group, it might be due to the cutting blades which are in a perpendicular direction at the scanned area, this was in accordance with our study.RadlanskiIn our study, the variation in burs cutting efficiency might be due to various factors which include, bur rotation speed, number of blades, pressure against the enamel during resin removal, and amount of time spent by the operator for the resin removal, that influence the changes that are observed here. previously advocated the use of burs at high speed in absence of water coolant. Subsequently, it resulted in heat in the pulp chamber followed by hyperaemia and sometimes ruptures of odontoblasts. Although, this phenomenon is temporary and reversible, thereby indicating healing of pulp tissue might occur within 20 days. Thus in this study, water cooling was used along with the TC burs during the resin removal procedures.Bicakci et alThis experimental study was conducted with laboratory conditions, so it is impossible to mimic the oral condition. The bond strength in in-vitro studies does not completely represent the oral environment. Although, with an increase in the number of samples, and the data showing parametric distribution, this standard experimental method was created to produce a laboratory condition that was as similar to the clinical scenario as possible, and thus extrapolation of the above in-vitro findings to the clinical situation is recommended for further in vivo and ex vivo investigations. Based on the results it could be concluded that:None of the composite removal methods was capable of re-established enamel to its earlier morphology. Application of low-speed 12 flutes TC bur found to be proven and the safe procedure for adhesive remnants removal irrespective of metal or ceramic brackets bonding techniques. An incremental increase in surface roughness parameters was reported after composite removal with a high-speed 12 flute TC bur, particularly for Rq and Rt measurements and which was statistically significant. However, the enamel loss observed was clinically insignificant, composite remnants removal by a high-speed 12 flute TC bur should be performed carefully. Application of low-speed 30 flute TC bur showed a moderate amount of surface roughness parameters in comparison with the other two burs.  No conflicts of interest. The study was approved by the institutional ethics committee in Albadar Rural dental college and hospital, Karnataka, India. No funding sources.