The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population.Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total.A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning  also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function.Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.The online version contains supplementary material available at 10.1186/s12967-022-03460-1. Chronic Fatigue Syndrome (CFS) is a condition that could significantly reduce the opportunity to undertake normal daily activities, in more severe forms might lead to inability to undertake even part time work and being chronically bedridden. There are no specified diagnostic markers nor differing diagnostic criteria commonly established .The global prevalence of CFS ranges between 0.4% and 2.5% and is growing; CFS affects 0.3–3.3% of the US population, 2.6% in the UK and 3% in China. In Poland, in cohort of people suffering from chronic fatigue the prevalence of CFS is 5% from and is associated with a significant symptom burden and impaired quality of life  to 4.2 ± 0.2 after WBC + SS (p = 0.0006), while in control group LWVI decreased from 4.7 ± 0.3 mmHg*l/[min*m2] to 3.9 ± 0.2, (p = 0.0004) . Post-hoc test indicates significant decrease of SI in response to WBC + SS in CFS group  . In CFS group TFC tended to increase, while in control group TFC tended to decrease after WBC + SS however, results of post-hoc tests were not significant (p > 0.05). Significant interaction between effects of group and WBC + SS on mean systolic ejection rate (MSER) was noted . In both groups MSER tended do decrease, post-hoc test revealed significant decrease in CFS group 311.6 ± 69 ml/s before WBC + SS vs 290.9 ± 70.6 after WBC + SS, p = 0.04) . In CFS group ER tended to increase, while in control group ER tended to decrease after WBC + SS, post-hoc tests showed that ER decreased in control group  , which decreased in HC group , and increased in the CFS group without statistical significance (p > 0.05). LFnu-RRI was higher in the control group vs CFS patients before WBC + SS  , which increased in HC group , and decreased in the CFS group without statistical significance (p > 0.05). HFnu-RRI was lower in control group vs CFS patients before WBC + SS  : both values tended to decrease in control and increase in CFS group, however changes were not statistically significant (p > 0.05). LF/HF dBP changed by interaction of effects of WBC + SS and group : it tended to decrease in control group and increase in CFS, however post-hoc analysis revealed no significant results. HFnu-sBP changed by interaction of effects of WBC + SS and group : it tended to increase in the control group and decrease in CFS, however post-hoc analysis revealed no significant results. LF/HF sBP changed by interaction of effects of WBC + SS and group : it tended to decrease in control group and increase in CFS. Post-hoc analysis revealed a significant decrease of LF/HF sBP in control group in response to WBC + SS  . Post-hoc analysis revealed that TMT A result decreased in the CFS group  and the control group . Moreover, the result of TMT A was significantly lower (better) after WBC + SS in the CFS group compared to the control group before WBC + SS  . Post-hoc analysis revealed that TMT B result decreased in the CFS group  and the control group . Moreover, the result of TMT B was significantly lower (better) after WBC + SS in the CFS group compared to the control group before WBC + SS  . WBC + SS led to reduction (i.e. improvement) in the number of digits left in coding after 1st and 2nd minute . Post-hoc analysis showed that in CFS group number of symbols left after 1st minute decreased from 52.8 ± 9.5 symbols left before WBC + SS to 47.8 ± 6.2 after WBC + SS (p = 0.0001) and after 2nd minute decreased from 12.7 ± 11.5 symbols left before WBC + SS to 6.1 ± 7.9 after WBC + SS (p = 0.0001). In control group number of symbols left after 1st minute decreased from 55.2 ± 7.3 symbols left before WBC + SS to 49.3 ± 8.1 after WBC + SS  and after 2nd minute decreased from 15.1 ± 11.1 symbols left before WBC + SS to 8.1 ± 9.1 after WBC + SS (p = 0.001). Results after I and II minute after WBC + SS in CFS group were better than in control group before WBC + SS  , to our knowledge, this is one of very few studies assessing the impact of short-term exposure to extreme cold on cognitive function, and the first to include patients with CFS , 27. IntThe mechanisms related to cognitive improvement after short-term extreme cold application are largely unknown. The only study using fMRI showed an increase in the ventrolateral prefrontal cortex activity in response to cold stimuli, allowing some insight into potential mechanisms at the neural level . AnotherInterestingly, both in our, and previous studies, cryotherapy improved selected cognitive abilities, while others were unaffected. For example, Theurot et al.  showed aAn important aspect of cryotherapy is its high tolerability. While good tolerance of cryotherapy has been consistently seen in case of many conditions, our study is the first to show it in CFS, with all included participants completing the study . This isGiven the preliminary data showing the beneficial effect of cryotherapy on cognitive function, its relative ease of application, good tolerability, and proven safety, therapy with extreme cold appears to be an approach worth attention. Further exploration of cryotherapy as a potential treatment for cognitive dysfunction in CFS is particularly important in light of the lack of effective therapeutic options for these common and often disabling symptoms.A WBC programme might also be considered as physical exercise programme mimetics due to the fact that it induces a pulsative expression of myokines  . AuthorsBoth pre-, per- and post cooling methods are applied in sport to improve athletes’ performance. Prolonged, intensive physical exercise sessions in high ambient temperature could lead to hyperthermia. Pre-cooling of subjects with physical exercise-induced hyperthermia has been shown to be beneficial for both aerobic and aerobic and cognitive performance, which are disturbed by hyperthermia . The undIn physical medicine, a variety of cooling methods can be applied, such as WBC, water immersion partial body cryotherapy, local cooling, etc. It seems, that there are differences in the physiological responses to those methods. For instance, a more pronounced decrease in blood flow and tissue temperature were noticed in response to cold water immersion in comparison to WBC  and coldIn addition, ATP is maintained at a similar level for at least a day between 10 to 37 degrees of Celsius, however, both utilization and synthesis are negatively corelated with temperature below 37 degrees of Celsius .Further studies should examine the effects of combined therapies in the management of symptoms in ME/CFS. As Senczyszyn et al. have noted, combinations of Computerized Cognitive Training (CCT), psychoeducation and WBC might be more effective in the reduction of depressive symptoms than Computerized Cognitive Training (CCT) and psychoeducation only . In addiWe have noted a decrease in daytime sleepiness, however sleep efficacy was not measured objectively in this study. Therefore, the above study results should be replicated on larger sample size with applied long-term follow-up, before recommending WBC as a supportive therapy in CFS.This study took place from January 2018 to July 2018 and was approved by the Ethics Committee, Ludwik Rydygier Memorial Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń (KB 660/2017). Written informed consent was obtained from all participants.A total of 250 individuals who identified themselves as fatigued, were recruited to the initial evaluation. Individuals who fulfilled the Fukuda criteria for CFS were eligible to enter the study if they were (1) age between 25 and 65 years, (2) fatigue more than 6 months, were severely fatigued, operationalized as scoring more that 36 on the Fatigue Severity Scale, (3) had at least four of additional symptoms: malaise after exertion, headache, impaired memory and/or concentration, unrefreshing sleep, sore throat, tender lymph nodes , muscle or joint pain, (4) the fatigue must not be the result of an organic disease . Patienthttps://glimmpse.samplesizeshop.org/#). Power was set on 0.9, alpha was set on 0.05. Hotelling Lawley Trace test was chosen, as it was advised to choose that option because of similarity with mixed effect linear model. Main effect of WBC + SS on score in FIS was chosen as the primary outcome of the study and decrease from 93.59 to 61.68 and standard deviation of 24.86 points in the CFS group was assumed based on our observation in a previous non-pharmacological intervention based study on CFS patients , systolic blood pressure [sBP], diastolic blood pressure [dBP], mean blood pressure [mBP], stroke index [SI], cardiac index [CI], total peripheral resistance index [TPRI], index of contractility [IC], acceleration index [ACI], left ventricual ejection time [LVET], left ventricular work index [LVWI], total fluid content [TFC], Heather index [HI], total artery compliance [TAC]; autonomic parameters: low frequency (LF), high frequency (HF) of heart rate variability (HRV) and blood pressure variability (BPV), ratio of LF to HF [LF/HF], baroreceptor slope mean. TFM automatically provides a power spectral analysis for HRV BPV which is conducted using the adaptive autoregressive model. All parameters were automatically measured at rest  and during an active standing test (AS).p-values for the main effects and their interaction are derived using the Satterthwaite approximation [p-values are provided and post-hoc tests analysis was conducted. Result of post-hoc tests were adjusted using Holm correction using lsmeans and multcomp packages [All data are presented as mean ± SD. Applicability of parametric tests were verified with the Shapiro–Wilk test and by visual inspection of histograms. To test the effects of WBC (before vs after) in CFS group on variables which values did not meet the normality of distribution assumption, were analysed using Wilcoxon signed-rank test, otherwise paired t-test has been used. To analyse the effects of WBC (before vs after) in groups (HC vs CFS), a linear model with random effect was applied using R statistical packages (Lme4 and LmerTest) were used  with a fximation . Resultspackages .Additional file 1: Table S1. Basic characteristics of the CFS/ME group and HC group. Table S2. Clinical characteristics of the CFS/ME group. Table S3. Details of presenting complaints of CFS/ME group. Table S4. Mean ± SD resting values of cardiovascular function indicators for subjects with CFS and HC. Table S5. Mean ± SD resting values of autonomic measures for subjects with CFS and HC. Table S6. CFS group mean values ± SD before-, after, and follow-up WBC + SS intervention for cognitive function


Few long‐term reports have been published on the epidemiology of respiratory viruses despite their frequent involvement in extremely common infections. The aim here was to determine the frequency and distribution of respiratory viruses in a temperate climate area  throughout a 24‐year period.We collected data on all respiratory viruses detected from 1997 to 2020 in our institution. Clinical specimens were analyzed mainly by conventional techniques, and molecular techniques were also used.Of the 59,579 specimens analyzed, 21,382 (35.9%) were positive for at least one virus. The number of positive samples during cold months was significantly higher than in warm months. Respiratory virus infections were detected in patients of all ages, above all in children under 3 years of age, who were most frequently infected with the respiratory syncytial virus, whereas Influenza A virus predominated in the other groups, especially in adults. A clear demographic and seasonal pattern was established for some viruses. Circulation of other respiratory viruses during the FLUAV H1N1pdm09 and SARS‐CoV‐2 pandemics was observed.This long‐term study provides new knowledge about the prevalence of respiratory viruses in a Mediterranean region. Throughout the study period, the frequency of some viruses remained constant, whereas others varied with the year. A clear demographic and seasonal pattern was established for some viruses. Patients suffering from severe respiratory infections should be examined for a range of respiratory viruses regardless of gender, age, or season. They have a wide range of clinical presentations, ranging from common colds to severe lower respiratory tract infections. As the same clinical presentation may be caused by different viruses and the same virus may manifest with different symptoms, microbiological diagnosis is essential to determine the etiological agent causing the infection.The few long‐term studies on respiratory virus epidemiology published to dateThe aim of the present study was to determine the frequency and distribution of respiratory viruses in a Mediterranean area throughout a 24‐year period, including the first months of the SARS‐CoV‐2 pandemic.22.1Hospital de la Santa Creu i Sant Pau approved the research  and waived the need for consent.We collected all the available data on respiratory viruses detected from January 1997 to March 2020 in our institution, a tertiary referral teaching hospital covering an area of 407,550 inhabitants in Barcelona (Spain). We analyzed the circulation of respiratory viruses, including frequency and seasonal distribution, the relationship between the different viruses detected, and two baseline parameters of patients (age and sex). The Ethics Committee of Patients were grouped according to their age: groups A (under 6 months), B (6–12 months), C (1–2 years), D (3–5 years), E (6–17 years), F (18–29 years), G (30–39 years), H (40–59 years), and I (over 60 years). All patients under 18 years of age were assigned to the pediatric population. Patients were classified as of unknown age when this information was unavailable.The clinical specimens analyzed were nasopharyngeal aspirates, nasal and pharyngeal exudates, bronchoalveolar lavages, and lung biopsies. The conventional techniques routinely used to identify respiratory viruses were immunochromatography, immunofluorescence (IF), and cell culture (CC), as described in the literature.Specimens received from March 2020 were only studied for the presence of SARS‐CoV‐2 due to the exceptionality of that year, and they were analyzed separately.2.2t test and Chi‐square test, respectively.Statistical analysis was performed by means of SPSS v26 . Continuous data and categorical data were analyzed using the 33.1p < 0.001).In the 1997–2019 period, 59,579 respiratory specimens were received by the laboratory, with a median of 2,590 per year . Of these, 49,712 samples were processed by conventional methods and the other 9,867 only by molecular methods. A total of 21,382 samples (35.9%) were positive for at least one virus. Overall, 21,939 virus detections were made, with more than one identified in 551 specimens (2.6%). The rate of positivity was significantly higher in samples acquired during the cold versus warm months, matching the seasonal distribution of samples received  respiratory virus detections were made. All specimens received after the WHO declaration of the SARS‐CoV‐2 pandemic were analyzed only for SARS‐CoV‐2. A total of 6,566 samples were positive for SARS‐CoV‐2 in 2020.3.2The different respiratory viruses identified throughout the study period are shown in Table p < 0.001); FLUAV ranged from 4% to 56.4%, with rates highest in 1999, 2000, 2014, and 2019 (p < 0.001); AdV, 4.3% to 20.7%, with a peak in 2007 (p < 0.001); EV, 1.6 to 20%, being highest in 2001 and 2010 (p < 0.001); and PIV3, 1% to 7.2%, with the highest rate in 2004 and 2006 (p < 0.001). After the introduction of routine testing for hMPV, this virus was detected every year (2008–2019) at rates ranging from 2.7% to 7.9%, with the highest in 2010 and 2011 (p < 0001) ; RV ranged from 0.1% to 12.6%, with the highest rate observed in 2004 (p < 0.001); PIV‐1, 0.1% to 6.6%, with peaks in 2001 and 2004; and PIV‐2, 0.1% to 4.6%, peaking in 1997 (p < 0.001) . Among the viruses detected in the cold months, RSV detection was highest from November to January, reaching a maximum in December. The prevalence of FLUAV was highest from December to March, normally reaching a peak in January, whereas for FLUBV, it was from January to March, with a peak usually 1 month after FLUAV. hMPV was most prevalent from February to May, and PIV‐2, from September to December, with a peak usually in November.The monthly distribution of each respiratory virus and their seasonal patterns during the 23 years prior to the SARS‐CoV‐2 pandemic are shown in Figures The other respiratory viruses in this study were detected throughout the year: AdV was most prevalent from November to May; EV and RV usually peaked in autumn and spring; PIV‐1, from September to April with a peak in October; and PIV‐3, from April to June and October to December.3.3The circulation of other respiratory viruses during the FLUAV H1N1 pdm09 pandemic (April 2009 to March 2010) was analyzed. Overall, 3,512 samples were screened for respiratory viruses during this period, 1,068 of which tested positive (30.4%) with a total of 1,080 virus detections (Table 3.4p < 0.001). Maximum virus detection occurred in patients of groups B and C , with 51.7% and 51.3% of samples testing positive, respectively. At least one virus was detected in 38.9%, 44.8%, and 32.1% of the samples from groups A, D, and E, respectively. RSV was the most frequently detected virus in patients under 3 years of age. FLUAV was predominant in the other groups, especially in patients over 18 years of age.The highest number of samples was collected from patients over 60 years (group I) and the lowest from those between 18–29 years (group F). The detection frequency for each respiratory virus varied between the different age groups Table , the difp < 0.001), with 43.1%  of all RSV cases identified in this group. The frequency of hMPV was highest in infants of group C  and group A  (p < 0.001). Of all FLUAV cases, 30.4%  and 15.3%  corresponded to groups I and C, respectively, and 34.7% of FLUBV detections  to group I. AdV was detected most frequently in group C (p < 0.001), with 40.1%  of all positive samples corresponding to this group of infants. Detection of EV and RV was higher in pediatric patients than in adults (p < 0.001). Both EV (n = 1461) and RV (n = 1003) were most frequently detected in group A . Detection of parainfluenza viruses was also higher in pediatric patients than in adults (p < 0.001), with the highest rates obtained in group A: 41.8% PIV‐1 (69/165), 34.6% PIV‐2 (44/127), and 37.2% PIV‐3 (204/548).The distribution of each virus was analyzed within the different age groups Figure . RSV wasn = 32,587) and 44.8%  of specimens were from males and females, respectively. Respiratory viruses were detected in 11,394 samples from males and 9,873 from females. Although more specimens were received from male patients, the percentage of positivity was higher for females (36.9%) than for males (34.9%) (p < 0.001). Differences in the positivity rates between the genders stemmed from the groups of patients more than 18 years old.Regarding the gender of patients, 54.6% (3.5n = 401), FLUBV (n = 223), RSV (n = 104), AdV (n = 46), hMPV (n = 28), RV (n = 16), EV (n = 13), and PIV‐1 (n = 1). In the second period, 905 specimens were analyzed for the presence of respiratory viruses other than SARS‐CoV‐2, and 30 (3.3%) of them were positive: FLUAV (n = 9), AdV (n = 8), RV (n = 7), FLUBV (n = 3), hMPV (n = 1), EV (n = 1), and PIV‐1 (n = 1). The results from 2020 were not included in the statistical analysis.The circulation of other respiratory viruses besides SARS‐CoV‐2 was recorded in 2020. This year was analyzed separately and divided in two periods, before and after the WHO declaration of the SARS‐CoV‐2 pandemic on March 15, 2020. In the first period, 2,903 specimens were analyzed for the presence of respiratory viruses other than SARS‐CoV‐2, and 832 (28.6%) of them were positive: FLUAV . However, over half of the respiratory viruses detected during the 2009/2010 pandemic corresponded to viruses other than FLUAV, in agreement with other regional laboratories.Overall, the highest positivity rates were observed in the pediatric population. All respiratory viruses may cause mild and self‐limited reinfections throughout a lifespan without requiring medical consultation, and therefore, the majority remains undetected. RSV was mainly diagnosed in children under 3 years of age, which may be partially explained by the high percentage of pediatric specimens (71.5%) included in our study, but also reflects that RSV infections are the main cause of respiratory infection (bronchiolitis) in infants.We observed an increasing tendency in FLUAV detection with patient age, as described in the literature.Our results showed that children aged 5 to 18 years were the population with most FLUBV infections, which is in agreement with other studies.Infections caused by PIV‐1 and PIV‐3 were mainly observed in infants under 6 months, whereas those caused by PIV‐2 were predominant not only in these patients but also in children aged 1 to 3 years. These results are comparable to those of Henrickson,The overall rate of virus detection in the present study was higher in females than in males, in contrast with previously reported data.In our study, using antigen detection and viral isolation methods, co‐detections were obtained in 2.6% of positive samples. These data are similar to those obtained by other studies based on conventional methodsIn this work, the most frequent co‐detection was of RSV and FLUAV, as reported in the literature,The impact of the COVID‐19 pandemic, declared during the preparation of this manuscript, on society and the medical network changed the study of respiratory viral infections. Accordingly, the highest number of specimens for the detection of respiratory viruses received in our laboratory in 1 year during the previous 23‐year period was 4,883, whereas in 2020, it was 66,616. That year, the number of specimens processed for the detection of respiratory viruses other than SARS‐CoV‐2 was 3,808, and 862 such detections were made, 96.5% of them before the pandemic declaration (data not published). Little information is available about the circulation of respiratory viruses other than SARS‐CoV‐2 during the rest of 2020 because all efforts were directed to SARS‐CoV‐2.A strength of this study is the use of gold standard methods, namely, viral culture and antigen detection immunofluorescence, together with the high number of samples and the long study period, as they provide a global vision of the prevalence of respiratory viruses in the area. A limitation of our study is that it was not based on systematic surveillance. Additionally, conventional methods are not the most suitable to detect certain viruses , although they are more reliable than molecular methods for the detection of an infection in progress. The changes in methodology  during the study period could have affected the number of detections, but the detection rates of the viruses in question were very similar in years when only conventional methods were used.This long‐term study therefore broadens our knowledge of the prevalence of respiratory viruses in a Mediterranean region. The frequency of some viruses was constant throughout the study period, whereas others varied with the year. Clear demographic and seasonal patterns were evident for some viruses. During the influenza A pandemic, other respiratory viruses were detected in more than half of patients suffering respiratory infections. Other respiratory viruses were also detected during the first year of the SARS‐CoV‐2 pandemic.This work was supported by own funding.https://publons.com/publon/10.1111/irv.12972.The peer review history for this article is available at


Pregnancy is a time of great physical and psychological change. As well as prominent changes in the external appearance of the body, such as the baby bump, there are also substantial changes taking place within the body. Our awareness of, and attention towards, internal bodily signals (interoception) is thought to have a direct impact on how we feel about our bodies. Therefore, understanding how our experience of these interoceptive signals might change during pregnancy may have important implications for maternal wellbeing. This study examined body satisfaction and interoceptive sensibility (subjective experience of interoception) in pregnant and non-pregnant women with and without children. Feelings towards pregnancy-specific changes in body satisfaction and interoceptive sensibility were also examined in women in their first pregnancy (primigravida) and subsequent pregnancies (multigravida). It was found that pregnancy did not directly impact levels of body satisfaction, instead pregnant and non-pregnant women with children reported less satisfaction with their bodies compared to those without children. Primigravida women were more satisfied with the appearance of pregnancy specific bodily changes compared to multigravida women. Interestingly, these differences in body satisfaction in those with children (pregnant and non-pregnant) were mediated by the extent to which women trusted their bodies (measure of interoceptive sensibility). All other pregnancy related changes in interoceptive sensibility and body satisfaction were either non-significant or had small effect sizes. These results may suggest body trust as an important factor to support during the transition to parenthood in order to improve body satisfaction in mothers. Much of the research to date examining women’s experiences of the body during pregnancy focuses on such external bodily changes, and how that makes her feel about herself and the fetus. For example, how women feel about and adapt to external bodily changes during pregnancy is thought to impact on mental health5 and physical health behaviours6. In addition, pregnancy body satisfaction is found to influence infant wellbeing through the development of antenatal attachment7 and breastfeeding intentions and duration8, which are important for infant development10.During pregnancy, an expectant mother experiences vast physiological and psychological adjustments in a relatively short period of time (approximately 40 weeks). Many of these changes are externally visible, such as the abdominal area protruding increasingly through the duration of the pregnancy (baby bump), weight gain11, which has a physiological basis correlating directly with activation in the anterior insular cortex12. There are three distinct mechanisms which are considered to form interoception13; interoceptive accuracy (or sensitivity), interoceptive sensibility and interoceptive awareness. Interoceptive accuracy refers to how accurate an individual is at detecting and interpreting interoceptive signals when compared with objective measures14. Conversely, interoceptive sensibility refers to the subjective experience of interoception, or how interoceptive signals are experienced irrespective of their objective reality15, primarily measured with self-report questionnaires. Finally, interoceptive awareness refers to the correspondence between objective interoceptive accuracy and subjective reports; metacognitive awareness of one’s own interoceptive accuracy13. Dysfunction in interoception is increasingly recognised as an important component of mental ill-health, including eating disorders18, depression and anxiety20 and schizophrenia21. Recent research suggests this is also the case during pregnancy22.There is noticeably less literature investigating the changes in internal bodily signals through pregnancy, and how such changes influence psychological wellbeing. The awareness of internal bodily signals such as heart rate, hunger and thirst is widely referred to as interoception23 and the heightened importance of hydration24. There are also changes in perception and experience of fatigue during the three trimesters25 and increased cardiac output26 resulting in increased body temperature27. Cardiac output, and notably detection of strength and speed of heartbeat are considered key markers of interoceptive accuracy13. Moreover, there are physiological experiences unique to the gestational period, such as pregnancy related pain28.During pregnancy women may experience many visceral changes, such as increased hunger and thirst due to greater required energy intake29, with advice from healthcare professionals to recognise and monitor fetal movements due to the importance for detecting potentially life threatening fetal anomalies30. Although movements of the fetus do not originate from the women's own body so may not constitute interoception in themselves, detecting such movements is likely to change the way women attend to their body. Additionally, fetal movements are also likely to impact interoceptive signals by additional noise or by directly affecting visceral organs such as the bladder. The way women attend to their body is also likely to change during pregnancy, with women listening to and trusting their body more when pregnant7. Feelings of trusting the body are thought to be important during pregnancy, specifically trusting the body to support the safe development of the fetus, which women have reported is a critical part of late pregnancy31, and trusting that the body will undertake the necessary requirements during labour32, such as knowing when to push.Awareness and understanding of these bodily signals may be important during pregnancy for the safety of the mother and fetus. There is an increased emphasis on listening to signals from within the body, such as fetal movements33, however, such scales have not been validated for pregnancy and do not dissociate between different aspects of body satisfaction. For this study we will use a body satisfaction scale that has been developed explicitly for pregnancy body satisfaction, the Body Understanding Measure of Pregnancy scale (BUMPs)7. This measure captures three separate aspects of pregnancy body satisfaction: Appearance, measuring satisfaction with the appearance of being pregnant; Weight, measuring concerns about pregnancy weight gain; and Physical, measuring frustrations with the physical burdens of pregnancy. Previous studies have suggested that changes in body satisfaction through pregnancy vary depending on the construct being measured. For example, women report feeling less fat during later stages of pregnancy, whilst other aspects are more stable34. Considering that perceived fatness is contrary to social ideals, and that women are more likely to look distinctly pregnant (opposed to overweight) the closer they are to birth, we predict that appearance dissatisfaction and weight concerns would decrease with gestational age. Conversely, due to the increasing size of the baby bump we would predict that frustrations with physical burdens of pregnancy would be higher for women further through pregnancy.The other aspect of bodily experience to be examined in the current study relates to how women feel about their external appearance (body satisfaction). Many studies examining body satisfaction in pregnant samples use scales which ask about satisfaction with different aspects of the body, such as the Body Cathexis Scale35 and lower self ratings of health36 than primigravida women (women in their first pregnancy). Primigravida women are also found to report lower levels of attention regulation (measure of interoceptive sensibility), which suggests that they are less able to sustain and control attention to their body than multigravida women, and this is associated with higher levels of anxiety22. In terms of exteroceptive body appearance, multigravidae women have been found to feel more negatively about their body than primigravidae31. For first time mothers, pregnancy involves many previously unexperienced bodily changes, and adjustments in awareness of her own physical state. Multigravida women, on the other hand, have already undergone perinatal bodily changes, and thus may know what changes to expect in their body37. Additionally perception of, and satisfaction with, bodily changes may depend on a comparison with the pre-pregnant self37. For primigravidae the pre-pregnant self could be very different to multigravidae’s pre-pregnant self, whose bodies have already been changed by previous pregnancies38 and may have experienced permanent changes to body shape and function40. Furthermore, non-pregnant women with children have been found to have a more positive relationship with food41, but less positive attitudes about bodily appearance42, suggesting that being a mother may have an impact on our experience of the body even outside of pregnancy.Because of the physical nature of pregnancy and birth, having already experienced this may impact on interoceptive and exteroceptive bodily experience. Multigravida women (women who have been pregnant before) report increased fatigue43. The MAIA consists of eight subscales capturing different constructs of interoceptive sensibility, including noticing and listening to signals from the body, not worrying about and not distracting from internal signals, body trusting, attention regulation, self regulation and emotional awareness. A recent study has suggested that many of these constructs change during pregnancy and into the postpartum period44.The current study aimed to assess changes in interoceptive sensibility and body satisfaction during pregnancy in primigravidae and multigravidae, as well as by comparing to non-pregnant women with and without children. Interoceptive sensibility will be assessed using the Multidimensional Assessment of Interoceptive Awareness (MAIA)44, we also predict that primigravida will report less attention regulation compared to multigravida women. Evidence suggesting that pain and interoceptive sensibility changes between early and late pregnancy47 leads to the prediction that there will be differences in the aforementioned constructs of interoceptive sensibility between women across gestation, specifically women will notice, listen and worry about signals more and distract less from internal signals (i.e. pain and discomfort) the closer they get to birth. We will also examine potential differences in the remaining interoceptive sensibility constructs  due to recent research suggesting these are greater during pregnancy compared to postpartum44. We also predict that permanent bodily changes from previous pregnancy/ies and birth will drive body satisfaction. Thus, women with children (pregnant and non-pregnant) will have lower body satisfaction compared to women in their first pregnancy and those without children.It is predicted that due to increased emphasis on bodily signals throughout pregnancy, pregnant women will report that they notice changes in their body, listen more to their body and trust their body more compared to non-pregnant women. Due to the increased importance of attending to the body, we also anticipate pregnant women will demonstrate less interoceptive avoidance and greater worrying, particularly amongst primigravida. In line with previous findings48. This inextricable relationship may suggest that changes in one aspect of the body can impact on the other. For example, those with poor interoceptive sensibility are also thought to have more negative experiences of their own body, and this has been found to be specifically linked with pregnancy body dissatisfaction7. Indeed, this relationship may be particularly important when pregnant due to the dramatic physiological changes occurring at this time. Therefore, it is crucial to understand if and how any interoceptive sensibility changes during pregnancy relate to exteroceptive bodily experience. Examining these aspects during pregnancy not only tells us something specifically about the prenatal bodily experience, but it may also help us better understand the mechanistic relationship between interoceptive and exteroceptive bodily signals and wellbeing more generally.A single coherent representation of the bodily self comprises both interoceptive and exteroceptive signals from the body, the latter of which includes body satisfaction7 and non-pregnant49 populations this subscale is predicted to play an important role in both general and pregnancy specific body satisfaction.Therefore, we also seek to examine how the link between interoception and external experience of the body (body satisfaction) might change as a result of pregnancy. This will be examined relative to pregnancy specific body satisfaction, and how this compares to non-pregnant women, considering body satisfaction more generally. It is anticipated that pregnancy induced changes in interoceptive signals, which are thought to be primarily driven by supporting the growing fetus, along with changes about how we feel about these signals in pregnancy, may weaken the relationship between body satisfaction and interoception and as such being pregnant will remain the strongest predictor for body satisfaction over and above interoceptive sensibility. Finally, due to the body trusting subscale on the MAIA being found to correlate most strongly with body satisfaction in both pregnant7 that consisted of women who had completed all the relevant measures (see below). The non-pregnant women were recruited to complete a separate survey to provide a control sample. Pregnant respondents were also categorised as being pregnant with their first baby  or a subsequent pregnancy , see Table The study was approved by the university departmental ethics committee at The University of York, and all procedures were performed in accordance with relevant named guidelines and regulations. Pregnant and non-pregnant women responded to separate advertisements to complete online surveys about bodily experience, and whether they had children, hosted on Qualtrics . The advertisements were distributed via social media sites , university staff newsletters, parenting websites, groups and classes, a local maternity ward and a maternity retailer. Informed consent was gained from all participants before commencing the study. The sample of 259 pregnant women was selected from a larger sample52. To eliminate possible confounds women in the postnatal period (up to 12 months postpartum) were also excluded. This non-pregnant subsample included women who reported having had children (n = 133) and those who reported not to have children . The majority of respondents from all groups were white, in a relationship and had an undergraduate degree or higher , under the age of 18 (n = 1), over the age of 41 (n = 131), had a baby within the last 12 months (n = 120) or had incomplete responses (n = 171), leaving a final sample of 241 women who were not currently pregnant at the time of the research. Women over the age of 41 were excluded in order to make the age range equivalent to the pregnant sample. Literature suggests there may be some residual effects of pregnancy associated with interoception such as changes to pain threshold and to levels of fatigue, that continue for several months after birth7. Each item relates to satisfaction with a part of the body or bodily functions, for instance: hands, body build, eyes, health, and weight. Responses are scored on a 5-point Likert scale, ranging from 1 (very dissatisfied) to 5 (very satisfied) and scored by summing all items. Higher scores indicate higher levels of body satisfaction. The scale has good test–retest reliability (0.89) and internal validity53 (α = 0.78–0.87). In the current study the internal validity is high for both pregnant (α = 0.92) and non-pregnant (α = 0.93) samples.The BCS is a self-report questionnaire that measures satisfaction with the body. For the current study an adapted version of the BCS was used consisting of 43-itemsThe MAIA is a 32-item self-report questionnaire measuring independent constructs of interoceptive sensibility. The scale consists of eight subscales, as outlined in Table 43. Internal reliability is good for all subscales in both pregnant (α = 0.65–0.90) and non-pregnant (α = 0.66–0.91) samples.Responses are made on a 6-point Likert scale, in which participants indicate how often each statement applies to them generally in daily life, with responses from 0 (never) to 5 . The score for each subscale is calculated by the mean of its individual items, with no global score. The MAIA is found to have good convergent and discriminant validity and acceptable internal consistencyBUMPs is a 19 item self-report questionnaire designed to capture body satisfaction specifically in pregnant women. The scale consists of three subscales, as illustrated in Table 7. The current sample is good for all scales (α = 0.74–0.90).Scores are calculated by summing items for individual subscales and all 19 items for a global score. Higher scores indicate higher levels of dissatisfaction. The measure is suitable for women across all three trimesters, with good internal consistency across all scales (α = 0.71–0.91) and good test–retest reliability (0.78–0.93)All participants completed the BCS and the MAIA, and the pregnant women additionally completed the BUMPs.Our hypotheses were tested using mixed ANCOVA and follow-up Bonferroni corrected independent t tests and Pearson’s correlations. Bayes factors are included for all follow-up t tests. To examine if interoception can predict both pregnancy specific and general body satisfaction we used hierarchical multiple regression. These analyses were also followed up with mediation analysis.p2 = 0.000, BF = 0.216) and no pregnancy * having children interaction  = 2.76, p = 0.097, ηp2 = 0.006, BF = BF = 1.1e+14). However, the main effect of having children was significant  = 82.3, p < 0.001, ηp2 = 0.143, BF = 1.76e+15) as those with children  were older than those without children . Therefore, age was used as a covariate in subsequent analyses.An ANOVA with the factors pregnancy (pregnant vs not pregnant) and having children (with children vs without children) was used to determine if age differed between groups. There was no main effect of pregnancy  = 0.19, p = 0.664, η7 and differing ways to compute the stage of pregnancy in the literature [e.g.54], we decided to analyse gestational weeks as a continuous variable and enter it as a covariate along with age.First, to test our hypothesis that multiparous women would have lower body satisfaction compared to primiparous and that dissatisfaction with appearance and weight concerns would reduce with gestation, whilst frustrations with physical burdens would increase, a 2 × 3 mixed ANCOVA was conducted on BUMPs subscale scores. The between factor was parity (primiparous vs multiparous) and the within factor was BUMPs subscale . Due to the under-representation of women in the first trimesterp2 = 0.071) although this was meaningless due to the inherent differences in subscale items and subsequent summed scores. There was also a significant main effect of parity  = 9.11, p = 0.003, ηp2 = 0.034). Both the main effect of gestation  = 1.32, p = 0.252, ηp2 = 0.005) and the main effect of age  = 3.0, p = 0.085, ηp2 = 0.012) were non significant. The main effects were further described by significant interactions.There was a main effect of BUMPs subscale  = 19.45, p < 0.001, ηp2 = 0.017). There was also a significant interaction between BUMPs subscale and gestation  = 3.59, p = 0.028, ηp2 = 0.014). There was no significant interaction between BUMPs subscale and age  = 1.59, p = 0.205, ηp2 = 0.006).As anticipated, there was a significant interaction between BUMPs subscale and parity  = 4.34, p = 0.013, η*  parity interaction and to determine which of the pregnancy body satisfaction constructs differed as a function of parity, three independent t tests were conducted correcting for multiple comparisons . In line with our hypotheses, there was a significant effect of parity on BUMPs appearance subscale supported by the Bayes factor (t(257) =  − 2.96, p = 0.003, d =  − 0.37, BF = 8.21) with multiparous women having greater dissatisfaction (M = 26.7) than primiparous (M = 24.1). Contrary to predictions there was no effect of parity on BUMPs weight subscale (t(257) =  − 1.29, p = 0.198, d =  − 0.16, BF = 0.30) or BUMPS physical subscale (t(257) =  − 0.96, p = 0.338, d =  − 0.12, BF = 0.21). These results suggest that parity does influence pregnancy specific body satisfaction in terms of satisfaction with appearing pregnant, such that women in their first pregnancy have higher body satisfaction than women in subsequent pregnancies. See Table To follow up the BUMPs subscale actor . No significant relationships were found between gestation and either BUMPS appearance subscale  or BUMPS weight subscale . These results suggest that gestation impacts pregnancy specific feelings towards the body in terms of the physical burdens of pregnancy, with which women become less satisfied the closer they get to birth.To follow up the BUMPs subscale To examine our next hypothesis that previously having children would drive dissatisfaction with the body more than pregnancy a two-way ANCOVA was conducted on BCS scores. Independent variables were pregnancy (pregnant vs not pregnant) and having children (with children vs without children).p2 = 0.029, BF = 39.9) such that women who have had children reported lower body satisfaction  compared to women without children . There was also a significant effect of pregnancy  = 3.95, p = 0.047, ηp2 = 0.008, BF = 1.23), with pregnant women having higher body satisfaction  than non-pregnant women . The interaction between pregnancy and having children was not significant  = 1.65, p = 0.20, ηp2 = 0.003). The effect of age was also not significant  = 3.45, p = 0.064, ηp2 = 0.007).As anticipated, there was a significant main effect of having children,  = 14.67, p < 0.001, ηIn order to examine our prediction that parity and gestation will impact interoceptive sensibility during pregnancy we conducted a 2 × 8 mixed ANCOVA. The between factor was parity (primigravida vs multigravida) and the within factor was MAIA subscale . Gestation was entered as a covariate along with age. See Table 2 = 0.02) and age  = 9.272, p = 0.003, ηp2 = 0.035). There was no significant main effect of MAIA subscale  = 1.58, p = 0.003, ηp2 = 0.006) or gestation  = 0.221, p = 0.638, ηp2 = 0.001).These main effects were better described by the interactions below.There was a significant main effect of parity  = 5.74, p = 0.017, ηp* parity interaction  = 2.72, p = 0.008, ηp2 = 0.011). There was also a significant interaction between MAIA subscale and gestation  = 2.87, p = 0.006, ηp2 = 0.011). There was no significant MAIA subscale * age interaction  = 0.56, p = 0.788, ηp2 = 0.002).There was a significant MAIA subscale * parity interaction eight independent t tests corrected for multiple comparisons  were conducted. As anticipated there was a significant effect of parity on body trusting (t(257) = 2.89, p = 0.004, d = 0.36, BF = 6.78). with primiparous women having greater body trusting  compared to multiparous .To follow up the MAIA subscale d = 0.25, BF = 0.94), not-distracting (t(257) =  − 0.52, p = 0.604, d = 0.065, BF = 0.16), not-worrying (t(257) =  − 1.25, p = 0.213, d = 0.15, BF = 0.29), attention regulation (t(257) = 0.066, p = 0.507, d = 0.08, BF = 0.17), emotional awareness (t(257) =  − 0.173, p = 0.863, d = 0.02, BF = 0.14), self regulation (t(257) = 1.78, p = 0.08, d = 0.22, BF = 0.61) or body listening (t(257) = 1.59, p = 0.112, d = 0.20, BF = 0.46) - see Supplementary Material Contrary to predictions, there were no significant effects of parity on noticing (t(257) =  − 2.02, p = 0.04, * gestation interaction eight Pearson’s correlations were conducted with a bonferroni critical alpha of 0.0063. Contrary to predictions, none of the relationships between the MAIA subscales and gestation survived corrections for multiple comparisons: noticing , not distracting , not worrying , attention regulation , emotional awareness , self regulation , body listening  and body trusting . See Table To follow up the MAIA subscale To specifically examine if interoceptive sensibility is influenced by being pregnant or already having children we conducted a 2 × 2 × 8 ANCOVA controlling for age as a covariate. The between factors were pregnancy (pregnant vs not pregnant) and having children (with children vs without children). The within factor was MAIA subscale .2 = 0.001), having children  = 10.20, p = 0.017, ηp2 = 0.02) and age  = 5.34, p = 0.021, ηp2 = 0.011). There was no significant main effect of pregnancy  = 1.01, p = 0.314, ηp2 = 0.002) .There was a significant main effect of MAIA subscale  = 5.93, p < 0.001, ηp2 < 0.001), MAIA subscale and age  = 0.85, p = 0.544, ηp2 = 0.002) or MAIA subscale, pregnancy and having children  = 3.22, p = 0.002, ηp2 = 0.006). There was a significant interaction between MAIA subscale and pregnancy  = 3.22, p = 0.002, ηp2 = 0.006), and between MAIA subscale and having children  = 3.22, p = 0.002, ηp2 = 0.006).There was no significant interaction between pregnancy and having children  = 0.217, p = 0.642, ηp* pregnancy interaction eight independent t tests corrected for multiple comparisons . These analyses allowed us to directly examine the hypothesis that interoceptive sensibility would be different in pregnant women compared to non-pregnant women. As expected, there was a significant effect of pregnancy on not distracting (t(498) =  − 2.99, p = 0.003, d =  − 0.27, BF = 7.42). Pregnant women reported higher scores  compared to non-pregnant women , suggesting that pregnant women avoid signals less compared to non-pregnant women.To follow up the MAIA subscale d = 0.21, BF = 1.37), not worrying (t(498) =  − 0.969, p = 0.333, d =  − 0.09, BF = 0.16), attention regulation (t(498) =  − 1.27, p = 0.204, d = 0.11, BF = 0.22), emotional awareness (t(498) = 1.16, p = 0.247, d = 0.10, BF = 0.19), self regulation (t(498) =  − 1.75, p = 0.08, d =  − 0.16, BF = 0.44), body listening (t(498) =  − 0.70, p = 0.488, d =  − 0.062, BF = 0.46) or body trusting (t(498) =  − 1.11, p = 0.269, d =  − 0.10, BF = 0.18).Contrary to predictions, there were no significant effects of pregnancy on noticing (t(498) =  − 2.33, p = 0.02, To follow up the MAIA subscale × having children interaction eight independent t tests corrected for multiple comparisons . These analyses allowed us to directly examine the hypothesis that interoceptive sensibility would be different in women with children compared to women without children.d = 0.36, BF = 189.8). Those without children reported greater body trusting  compared to those with children .As anticipated, there was a significant effect of having children on body trusting (t(498) =  − 3.98, p < 0.001, d = 0.20, BF = 1.04), not distracting (t(498) =  − 1.8, p = 0.073, d = 0.16, BF = 0.48), not worrying (t(498) = 0.251, p = 0.802, d = 0.02, BF = 0.10), attention regulation (t(498) =  − 0.405, p = 0.685, d =  − 0.04, BF = 0.11), emotional awareness (t(498) = 0.419, p = 0.675, d = 0.04, BF = 0.11), self regulation (t(257) =  − 1.72, p = 0.086, d = 0.15, BF = 0.42) or body listening (t(498) =  − 1.79, p = 0.075, d = 0.16, BF = 0.47). See Table Contrary to predictions, there were no significant effects of having children on noticing (t(498) =  − 2.20, p = 0.028, To examine predictions that constructs of interoceptive sensibility, particularly body trusting, would be significant predictors of feelings toward pregnancy specific body changes, we ran a forced entry hierarchical multiple regression on our pregnant participants with BUMPs total score as the outcome variable  = 0.574, p = 0.449). In stage two we entered gestation and parity, the model was significant  = 3.30, p = 0.021) accounting for 2.6% or the variance. Whether or not women were in their first pregnancy was the only significant predictor  = 3.02, p = 0.003). In stage three we added MAIA subscales: noticing, not distracting, not worrying, attention regulation, emotion awareness, self regulation, body listening and body trusting. The model was significant  = 8.08, p < 0.001) accounting for 23% of the variance. The only significant predictor was body trusting  = − 7.03, p < 0.001). Whether or not the women were in their first pregnancy was no longer significant.lavaan package). The regression coefficients between parity and body trusting  and between body trusting and pregnancy body satisfaction (BUMPS) were significant  as well as the indirect effect . The regression coefficient between parity and body satisfaction (BUMPs) was not significant . See Fig. To follow up the significant effect of the body trusting subscale on pregnancy specific body satisfaction (BUMPS) we conducted a mediation analysis, with parity as the independent variable, BUMPs as the outcome variable and body trusting as a potential mediator. The mediation analysis was conducted in Rstudio = 0.039, p = 0.844). In stage two we entered whether or not the women were pregnant and whether or not they had children already. The model was significant, accounting for 2.8% of the variance  = 5.84, p < 0.001). The only significant predictor was having children  = 3.77, p < 0.001). In the third stage we added MAIA subscales: noticing, not distracting, not worrying, attention regulation, emotion awareness, self regulation, body listening and body trusting The model was significant  = 26.12, p < 0.001) accounting for 35% of the variance. Significant predictors were noticing  =  − 2.94, p = 0.003), not distracting  = 2.02, p = 0.044) and body trusting  = 13.73, p < 0.001). Whether or not the women had children was no longer a significant predictor.lavaan package). The regression coefficients between children and body trusting  and between body trusting and body satisfaction (BCS) were significant  as well as the indirect effect . The regression coefficient between children and body satisfaction (BSC) was not significant . The results suggest that the effect of having children on body satisfaction is fully mediated by body trusting, see Fig. To follow up the significant effect of the body trusting subscale on body satisfaction we conducted a mediation analysis, with having children (with vs. without children) as the independent variable, BUMPs as the outcome variable and body trusting as a potential mediator. The mediation analysis was conducted in Rstudio. Body trusting was found to be reduced in women with children and was the strongest predictor of both general and pregnancy specific body satisfaction. Additionally, there was a difference in interoceptive avoidance between pregnant and non-pregnant women, such that pregnant women distracted less from feelings of pain and discomfort compared to non-pregnant women. During pregnancy there was a significant effect of gestation on feelings towards the physical burdens of pregnancy, with women feeling more frustrated/negative about pregnancy related physical constraints the closer they got to birth. None of the other constructs of interoceptive sensibility and body satisfaction were significantly different between pregnant and non-pregnant samples or with those who have children. Age had no significant effects on individual constructs of body satisfaction or interoceptive sensibility.56, some a worsening58 and others suggesting relative stability in body satisfaction59. It has been proposed that these mixed findings represent a heterogeneous experience during the perinatal period7, which is often reflected in qualitative studies (e.g.60). Here, we found that pregnant women were less dissatisfied with their body than non-pregnant women. However, we also suggest that the parental status of both the pregnant and the comparison group may be an additional contributing factor to the prior (seemingly contradictory) results. Rather than body satisfaction being specifically related to pregnancy, it seems that whether or not women already have children is a stronger factor influencing how women feel about their body, with women who have had children reporting lower body satisfaction than women without children. Such decreases in body satisfaction may be due to permanent changes to the body as a result of pregnancy40, changes in social status, such as motherhood not being associated with attractiveness61, as well as changes in self identity and social role62. Furthermore, women with children also have less time to meet their own needs, at least when the child(ren) is young63, resulting in women having less time to focus on their own appearance and thus negatively impacting body satisfaction. This suggests that findings of relative differences in body satisfaction would depend, at least in part, on parity status of a pregnant sample as well as parental status of a control sample.There are mixed findings in the literature regarding body satisfaction during pregnancy, with some studies suggesting an improvement40 and thus undermine trust. The act of birth itself may also influence body trust. Health practitioners’ observations of signs of birth trauma suggest that trauma in relation to birth could impact over a third of new mothers, with ongoing implications on wellbeing64. Moreover, recent qualitative research found that as much as 65% of new mothers feel some sort of failure in relation to birth65. The authors suggested that feelings of self-perceived failure surrounding birth are driven by self-imposed and societal expectations. For many women deviation from what is perceived as an ideal ‘natural birth’, such as involvement of medical interventions, can be seen as failing to birth ‘properly’ and even failing their baby. Such medical interventions can range from emergency c-sections to following medical protocols or taking pain medication. Some of the participants reported that agreeing to such medical interventions was felt as a personal weakness, that they were not tough enough or lacked the mental and/or physical strength to birth naturally but also that their body didn’t work properly and was out of their control. Given that the act of giving birth is so physical, feelings of failure or trauma from birth may serve to undermine women’s trust in their body and thus may make women who have children more vulnerable to negative feelings about their body. Although these interpretations are speculative, these current results may have important implications on how women are supported through their transition to parenthood to assist their ongoing wellbeing and facilitate body trust and thus body satisfaction. Whether or not the reported lower body satisfaction and body trusting in women with children is driven by physical or social changes, or a combination of these, we suggest that such factors need to be considered when examining differences in bodily experience before, during and after pregnancy.Although both the social and physical factors are likely to play a role in how mothers feel about their body, the significant role of body trusting on levels of body satisfaction may suggest that physical aspects are more important. Indeed, for both general and pregnancy specific body satisfaction, the relationship between feelings towards the body and having had children was fully mediated by body trusting. This means that the mechanism through which women with children (pregnant or not) have lower body satisfaction may be via changes (worsening) in body trusting. One reason for a reduction in body trusting could be physical consequences of previous pregnancy and birth. Many women experience permanent physical changes as a result of previous pregnancy and birth, which may impact the way in which the body functions67. Therefore, the sort of discomfort captured by the MAIA may be anticipated during pregnancy and thus may not lead to additional worry. On the other hand, the experience of worry may relate to an intuitive link to the wellbeing of the fetus, but demonstrate a heterogeneous experience across women, similar to that observed with body satisfaction. Therefore, considering the individual experience, or longitudinal changes may be more important rather than studying global differences between pregnant and not pregnant samples.Somewhat surprisingly, pregnant women demonstrated equivalent worry about their bodily signals compared to non-pregnant women. Intuitively it might seem that pregnant women would show more worry when attending to their body because of the additional concern regarding the wellbeing of the fetus. However, when considering the nature of the questions in the not worrying subscale of the MAIA, the focus is on pain and discomfort, for example, “I can notice an unpleasant body sensation without worrying about it”. Pain is a common and intrinsic part of pregnancy; it has been suggested that the prevalence of lower back and pelvic pain in pregnant women is over 70%44. Although the listening subscale of the MAIA includes an item which may be very relevant to pregnancy and labour/birth “I listen to my body to inform me about what to do”, the other two items focus on attention to the body in relation to emotions; “I listen to information from my body about my emotional state” and “When I am upset, I take time to explore how my body feels”. Therefore, the MAIA may not be able to capture specific changes in how we attend to our bodies during pregnancy and the way in which pregnant women respond to these items may not be equivalent to responses outside of the perinatal period. Similarly we did not find a significant effect of noticing and indeed, for the majority of our predictions involving the MAIA subscales, we did not find significant differences in interoceptive sensibility between pregnant and non-pregnant samples as well as finding no evidence for changes relative to gestational age. This may be that the scale does not capture relevant constructs or it may well reflect a stability of subjective interoceptive experience throughout the perinatal period, with individual differences in the measures being potentially more important for wellbeing.Pregnant women reported reduced distracting from bodily signals  compared to non-pregnant women. This suggests that women avoid feelings of pain and discomfort less when they are pregnant. This may be due to health concerns for the fetus, wanting to be aware of early signs of labour or just being allowed to feel uncomfortable during pregnancy due to the clear visual marker of discomfort (baby bump) and a social expectation of discomfort during pregnancy. Contrary to our predictions, we did not find a significant effect of pregnancy or gestation on body listening. It was anticipated that pregnant women may listen to their body more for signals relating to the fetus, such as fetal movement, hunger and even signs of labour later on in pregnancy. A previous longitudinal study did find increased listening during later compared to early pregnancy and compared to the postpartum34, whereas other research suggests that body image worsens in the third trimester58. The current results suggest that women later in pregnancy have more negative feelings about physical burdens of pregnancy. Together, these results suggest that the point during pregnancy at which measures were taken could also affect outcomes of the measurements.We also found evidence for differences in frustrations with physical burdens of pregnancy across gestation. Previous studies have also reported that different aspects of our bodily experience change in different ways during the course of pregnancy. For example, it has been found that during the final trimester of pregnancy, women felt less fat compared to at any other time in pregnancy and their retrospective account prior to pregnancy71, therefore these aspects should be considered in future research.When considering the current findings we have to do so in the context of the study limitations. Firstly, it should be noted that as this was a cross-sectional study, changes in interoceptive sensibility can only be inferred. Therefore, although we find evidence for differences between groups and throughout gestation, to assess whether these experiences change over the perinatal period our findings should be further examined in longitudinal studies. Additionally, a main factor examined by this study is comparing women with and without children with the assumption that those with children had undergone the experience of pregnancy and childbirth. The survey asked participants how many children they had, not whether they had previously been pregnant before or if they had given birth, which in some circumstances could be ambiguous for example for women who have adopted, or used surrogacy. Likewise having been pregnant before does not necessarily mean the same as having children, due to adoption, miscarriage or stillbirth. Future work examining these questions in women who have children, but without ever giving birth and women who have been pregnant, but without raising children, may help tease apart the relative roles of social and physical factors to interoceptive sensibility and body satisfaction. The current sample is also compromised by a lack of inclusiveness, such that the sample consists predominantly of white, middle class, cis-gender women. We know that culture, ethnicity, gender and socioeconomic status can be important for social norms, body satisfaction and even maternity care72 and interoception75, particularly with women76 and in relation to high BMI and obesity77. A key physical symptom during pregnancy is weight gain therefore such measures as pre-pregnancy BMI and pregnancy related weight gain may play a key role in interoceptive experience during the perinatal period as well as body satisfaction. Future studies should aim to capture this information to specifically examine how it relates to the link between body trusting and body satisfaction. This may be particularly important relating to body trusting and weight gain. A previous study found that the weight subscale of BUMPs correlated with body trusting, which was interpreted as a greater trust in the body would mean that women would trust any weight gain to be essential for the healthy development of the fetus7. However, this relationship is likely to be moderated by actual weight gain, such that excessive weight gain in pregnancy may compromise body trust. Thus, future research should specifically examine this relationship.Another limitation with the current study is the absence of Body Mass Index (BMI) data. BMI and body size are thought to relate to both body satisfaction78, which may draw into question how meaningful some of the above mentioned effects are. However, more recently it has been suggested that even small effect sizes can be valuable especially in complex fields such as mental health, including body (dis)satisfaction, and the effect sizes found were comparable with other meaningful texts related to bodily experience in pregnancy (e.g.79). With such complex phenomena it is unlikely that single constructs or mechanisms underlie individual differences, and even small effects can have a big impact on those who are already vulnerable80. Additionally, due to the fact that the MAIA is not developed for, or validated in, pregnant women, we may also be missing important interoceptive changes, which are not captured by this measure, and thus underestimating interoceptive changes at this time. Much of the MAIA scale focuses on pain and discomfort, and whilst this is relevant in pregnancy, other aspects of interoception, such as hunger and thirst, may be attended to differently during pregnancy and may also have implications on body satisfaction through weight gain. Likewise it is important to consider which elements of body satisfaction measures such as the BCS are capturing. This is particularly the case during pregnancy, given that the BCS asks specifically about satisfaction with certain body parts. It has been proposed that there is a change in emphasis concerning the body during pregnancy60, it is therefore conceivable that pregnant women are responding more in terms of satisfaction with the function of certain body areas, whereas non-pregnant women may respond more in terms of appearance and so we may not be comparing equivalent constructs between the groups. Another potential issue to consider is in relation to current definitions of what sensations interoception refers to. Many of the MAIA subscales refer to pain and discomfort: whilst all types of pain are included in recent liberal definitions of interoception81, it is conceivable that these sensations may derive from an exteroceptive source. Accepted definitions of interoception have moved from very restrictive, only involving the viscera, to more inclusive criteria, including all sensations which follow specific ‘interoceptive’ neural pathways81. Such inclusive definitions not only include all types of pain, but also certain types of touch82. Scales, such as the MAIA focus predominantly on these more liberal constructs of interoception opposed to traditional elements like hunger and thirst and as such may be missing key elements of the interoceptive experience, particularly during pregnancy. Moreover, particularly when considering interoceptive sensibility, broad interoception definitions may be even more difficult to truly capture, given potential individual differences in the subjective experience of their body as well as item interpretation (i.e. we do not know what sort of pain they are referring to). This is also impeded by the observations that interoceptive sensibility measures like the MAIA do not tend to correlate with more objective measures of interoception83 and this also seems to be the case during pregnancy22, which means these measures are difficult to fully validate. However, despite these shortcomings, the MAIA is an accepted and well used measure of interoceptive sensibility. Future work should specifically aim to examine interoceptive experience in pregnancy and the suitability of scales like the MAIA to capture such constructs.Finally, it is important to note that some of the effect sizes of the current results are relatively small. Even though our key findings are supported by Baysian statistics, thus suggesting they are unlikely to be false positives, it has been suggested that small effect sizes do not provide information that is relevant to everyday thoughts and feelingsDespite these limitations, our current results suggest that body satisfaction is reduced in women who already have children, with a higher impact than pregnancy status, thus parental status should be examined in studies assessing level and impact of body satisfaction in pregnant and non-pregnant samples. Importantly, this relationship between having had children and body satisfaction is mediated by body trusting and thus highlights a key area of future research for body satisfaction interventions. Avoidance of interoceptive signals was also found to vary during pregnancy. However, existing measures are limited in scope of interoceptive signals, which may not be relevant to pregnancy and thus may be underestimating interoceptive changes during the perinatal period.Supplementary Information.


Janus kinase (JAK) inhibitors have become promising treatments for atopic dermatitis (AD), however no study directly comparing JAK inhibitors with each other has been reported. We conducted this network meta‐analysis to determine the comparative efficacy and safety of three common oral JAK inhibitors including abrocitinib, baricitinib, and upadacitinib for moderate‐to‐severe AD. We first identified eligible studies from published meta‐analyzes, then we searched PubMed to obtain additional studies published between February and July 2021. Clinical efficacy and safety were evaluated as primary and secondary outcome, respectively. After extracting data and assessing methodological quality, we utilized ADDIS 1.4 software to conduct pair‐wise and network meta‐analyzes. Ten eligible studies were included in the final analysis. Pooled results that abrocitinib, baricitinib, and upadacitinib obtained higher investigator global assessment (IGA), eczema area, and severity index (EASI) response, however abrocitinib and upadacitinib caused more treatment‐emergent adverse events (TEAEs) regardless of doses, compared with placebo. Network meta‐analyzes revealed that upadacitinib 30 mg was superior to all regimens and upadacitinib 15 mg was better than remaining regimens except for abrocitinib 200 mg in terms of IGA and EASI response. Moreover, abrocitinib 200 mg was superior to abrocitinib 100 mg, baricitinib 1 mg, 2 mg, and 4 mg for clinical efficacy. However, upadacitinib 30 mg caused more TEAEs. Abrocitinib, baricitinib, and upadacitinib were consistently effective therapies in adult and adolescent patients with AD; however, upadacitinib 30 mg may be the optimal option in short‐term studies. More efforts should be done to reduce the risk of TEAEs caused by upadacitinib 30 mg. Two independent reviewers conducted the literature search. Details of search query for PubMed were summarized in Table 2.2We first imported records from PubMed and published meta‐analyzes into EndNote software, and then removed duplicates. Next step, we removed irrelevant records through screening the titles and abstracts of records. Finally, we accessed the full text of all potentially eligible studies and determined eligible studies through checking eligibility. Two independent reviewers conducted study selection in order to avoid selection bias. In the event of any disagreement, a third senior reviewer contributed to the discussions.2.3We only included randomized controlled trials (RCTs) in this network meta‐analysis in order to avoid potential selection and confounding bias.2.4According to a previous meta‐analysis, the efficacy outcomes2.5Two independent reviewers conducted data extraction. The following data were extracted from eligible studies including: general information , patient characteristics , details of the targeted JAK inhibitors , and outcomes (efficacy and safety). Details of the risk of bias were also extracted to assess the methodological quality. In the event of any disagreement, a third senior reviewer contributed to the discussions.2.6Two independent reviewers assessed the risk of bias with the CC risk of bias assessment tool.2.7www.drugis.org) to conduct all statistical analyzes, and network meta‐analysis was conducted based on Markov Chain Monte Carlo (MCMC) simulation. The following parameters were used to estimate results of network meta‐analysis including 4 chains, 20,000 tuning and 50,000 simulation iterations, thinning interval of 10, 10,000 inference samples, and variance scaling factor of 2.5.We utilized the aggregate data drug information system (ADDIS) software , (b) ineligible participant (n = 1), and (c) unrelated to topic (n = 37). On the other hand, we obtained 12 potentially eligible publications from published meta‐analyzes, and 9 studies were considered to meet our selection criteria after excluding 3 ineligible studies according to 2 reasons including (a) ineligible participant (n = 1) and (b) ineligible treatment regimens (n = 2). Finally, a total of 10 studies  meta‐analysis , the Department of Science and Technology of Sichuan Province (Grant No. 20YFS0435), the Health Care of Sichuan Provincial cadres (2020–227), Science & Technology Bureau of Chengdu (YF05‐00198‐SN and YF05‐00060‐SN) and the Sichuan Academy Medical Science & Sichuan Provincial People Hospital (2018LY01).The authors declare that they have no conflict of interest.Table S1: Search strategy of PubMedTable S2. Pooled results from network meta‐analysis after conducting subgroup analysis according to the most common doses.Click here for additional data file.


Forced‐diuresis during cardiopulmonary bypass (CPB) can be associated with significant electrolyte shifts. This study reports on the serum electrolyte changes during balanced forced‐diuresis with the RenalGuard® system (RG) during CPB.2, anticipated CPB time >120 min, Log EuroScore >5)—were randomized to either RG (study group) or managed as per current practice (control group).Patients at risk of acute kidney injury (AKI)—. Mean urine output was significantly higher in the RG group during surgery . The serum potassium levels were maintained between 3.96 and 4.97 mmol/L for the RG group and 4.02 and 5.23 mmol/L for the controls. Median potassium supplemental dose was 60 (0–220) mmol (RG group) as compared to 30 (0–190) mmol for control group over first 24 h (p < .001). On Day 1 post‐op, there were no significant differences in the serum sodium, potassium, calcium, magnesium, phosphate, and chloride levels between the two groups. Otherwise, postoperative clinical recovery was also similar.The use of RG reduced AKI rate (10% for RG and 20.9% in control, Balanced forced‐diuresis with the RG reduced AKI rates after on‐pump cardiac surgery compared to controls. Although the RG group required higher doses of IV potassium replacement in the postoperative period, normal serum levels of potassium were maintained by appropriate intravenous potassium supplementation and the clinical outcomes between groups were similar. AKIacute kidney injuryCICUcardiac intensive care unitCINcontrast induced nephropathyCONSORTConsolidated Standards of Reporting TrialsCPBcardiopulmonary‐bypass machineCVPcentral venous pressuree‐GFRestimated‐glomerular filtration ratei.vintravenousKDIGOKidney Disease: Improving Global OutcomesKIDNEYstudy Kidney protection using the RenalGuard® system in cardiac surgeryMAPmean arterial pressureNKCC2sodium potassium chloride co‐transporterORoperating roomRGRenalGuard® systemRIFLERisk, Injury, Failure, Loss of kidney function, End‐stage renal diseaseR & DResearch & DevelopmentSDstandard deviationTALthick ascending limb1The development of acute kidney injury (AKI) after cardiac surgery has been reported to be associated with significant postoperative morbidity and mortality both in the short‐term and the long‐term.The principles and components of RG have been extensively described in previous reports.It is well recognised that diuresis, especially by loop diuretics, is associated with electrolyte losses. The loop diuretics block the NKCC2 (sodium potassium chloride co‐transporter) channels present on the apical membrane of the thick ascending limb of the loop of Henle causing sodium and potassium excretion in the urine.This randomised control trial assessed the electrolyte changes (secondary outcomes) between patients treated with balanced forced‐diuresis (RG group) compared to controls, during cardiac surgery and within the first 24‐h post‐op, along with the clinical impact during the in‐hospital stay.22.1Kidney protection using the RenalGuard® system in cardiac surgery) was reviewed and approved by the Institutional Research Committee (16CARD13) before seeking Ethical committee  approval and was registered on ClinicalTrials.gov website (NCT02974946). The study was also supported by the National Institute of Healthcare Research, Clinical Research Network, United Kingdom (NIHR ID: 32769). All recruited patients gave written informed consent to partake in the study. Trial patients were treated according to the Declaration of Helsinki 2013.The KIDNEY study  in patients undergoing cardiac surgery. Baseline creatinine was defined as latest creatinine level available before surgery. Secondary aims included the electrolyte changes during surgery and within 24‐h post‐op as well as their impact on clinical outcomes during hospital stay. The primary outcome has already been published2.32, (iii) Logistic Euroscore of 5 or above, (iv) haemoglobin level of 12.5 g/dl or below and (v) cardiac procedures when CPB time was likely to exceed 120 min.The inclusion criteria for recruited patients were one or more of the following: (i) diabetics (insulin or noninsulin dependent diabetes mellitus), (ii) eGFR of 20–60 ml/min/1.73 m2.42. Bypass was performed at mild to moderate (32–34°C) hypothermia and patients were warmed to nasopharyngeal temperature of 36.5–37°C and bladder temperature of >35°C before discontinuation of CPB. The cardioplegia soution  had the following constituents: sodium—147 mmol/l, potassium—84 mmol/l, calcium—2 mmol/l, magnesium—80mmol/l, procaine—5 mmol/l and chloride 400 mmol/l. This was mixed with cold blood in a ratio 1:4 for myocardial protection during surgery.A research‐independent person based in the Research & Development department devised and managed a sealed opaque envelope system for randomisation of consented patients. In patients randomised to the RG system, balanced forced diuresis was started in anaesthetic room after patient intubation and continued throughout the cardiac procedure in the operating room (OR) and for up to 6 h after cardiac intensive care unit (CICU) admission. Forced‐diuresis was initiated with 20 mg bolus of IV furosemide. In some patients, the urine output rate was maintained by a furosemide infusion which was titrated to 10 mg/hour during surgery, with the aim of achieving a urine output of at least 200 ml/hour. This infusion was stopped in the OR at the end of procedure. In this study, patients were managed at a zero balance i.e. volume of urine output was matched in real‐time to the volume of Hartmann's fluid replacement infusion given through the RG system. On CICU, the RG system was continued for 6 h (matching Hartmann's i.v infusion rate to urine output rate). Additional furosemide bolus (20 mg i.v) was administered whenever the urine output fell below the 200 ml/hour threshold within the first 6‐h postadmission to CICU. Control group patients were managed as per current medical practice. They did not receive i.v furosemide in the OR. Otherwise, the management of the patients was similar including the anaesthetic technique and cardiopulmonary bypass run including the need for inotropic support to maintain a mean arterial pressure (MAP) >65 mmHg. CPB‐flow was calculated and maintained at a cardiac index of 2.4 l/min/m2.5χ2) test of independence. Continuous variables are expressed as median  or mean (SD) for skewed and Gaussian distributed data, respectively. Group comparison was carried out using two‐tailed t test or Mann–Whitney U test accordingly. Repeated measures were analysed via the generalised linear model for the changes in the variables  across the various time points between the two groups and adjusted for any differences by the Bonferroni corrections. The tests were considered significant at p < .05. SPSS version 26.0 (IBM SPSS statistics 26) was used for statistical analyses.To achieve the primary end‐point with a power of 0.8 and an alpha of 0.05, 110 patients per group were deemed adequate as per the power calculations. Categorical data are expressed as percentages and differences between the two groups assessed using the chi square .A total of 220 patients were randomised to the study (110 patients per group). Pre and intraoperative patients' data were not significantly different between the two groups (Table p < .001).The secondary aims of mean volumes of urine produced during surgery (2366 ± 877 ml vs. 765 ± 549 ml) and within first 24‐h post‐op on CICU (3310 ± 1303 ml vs. 2052 ± 804 ml) were significantly higher in RG group (p = .8). Patients in RG group received a median dose of 28  mg i.v furosemide in the OR. On the CICU 61% of study group  and 53% of control group  received i.v furosemide within the first 24 h of CICU admission (p = .99). There were no statistically significant differences between the groups in terms of the MAP and CVP during surgery and on the CICU. Similarly, there was no significant difference between (a) the haemoglobin levels during and after surgery , inclusive of intraoperative transfusions.The median volumes of cold blood cardioplegia used were 2070 995, 5381) ml and 1933  ml, respectively ( ml and 1p < .001). The serum potassium levels were maintained between 3.96 and 4.97 mmol/L for the RG group and 4.02 and 5.23 mmol/L for the controls. The changes in the strong ion difference ([Na+ + K+ + Ca2+ + Mg2+ levels] minus [Cl− + lactate levels]) are shown in Figure Patients in the study group required significantly higher doses of i.v potassium supplementation to maintain normal serum levels, with median potassium supplemental dose being 60 0–220) mmol for RG as compared to 30 0–190) mmol for control group over 24 h , postoperative cerebro‐vascular events rate and median durations of CICU stays between the two groups. The median in‐hospital stay was 6 days for both groups.One patient in RG group and two patients in control group died before hospital discharge. Causes of death were not related to the use of device and included cardiogenic shock, cardiac failure and sepsis (pneumonia) respectively.4The primary aim of this study was confirmedPolderman reported electrolytes depletion in patients undergoing surgery with the CPB machine. The author suggested that these could be due to the intracellular shifts of electrolytes which are induced by hypothermia as well as urinary excretion of these electrolytes which was independent of the use of perioperative diuretics.Another important aspect which could influence electrolytes shifts is the acid–base status of the patient in particular, alkalosis.+, K+ , Ca2+ , Mg2+ levels minus the sum of Cl− and lactate levels). As for the weak‐acid, it consists of albumin and phosphate in the extracellular fluid, whereas within erythrocytes, it is primarily haemoglobin. An isolated increase in weak‐acid or a decrease in strong ion difference creates a metabolic acidosis. Changes in opposite directions, respectively, cause a metabolic alkalosis. In normal individuals not undergoing surgery a strong ion difference of around 40–45 mEq/L is considered normalThe use of CPB circuit is recognized to lead to metabolic acidosis possible as a consequence of bicarbonate dilution.The CPB circuit also causes significant haemodilution, hypomagnesaemia, and hyponatraemia. Haemodilution, as also discussed, causes acid–base changes. The degree of haemodilution can be minimized by using the retrograde autologous priming technique (RAP) where the priming volume is kept to around 1 L.4.1This was a single centre study. Moreover, as the study was not blinded, the management of the control group could have been influenced by some aspects of the Hawthorne effect.5In patients at‐risk for AKI, undergoing cardiac surgery with CPB, balanced forced‐diuresis as provided by the RG system significantly reduced the incidence of AKI. Compared to the control group, serum potassium levels were lower in the RG group. However, normal levels could be maintained by administration of IV potassium replacement in the postoperative period, thus maintaining similar clinical outcomes, with no adverse safety concerns.The authors declare that there are no conflict of interests.Concept and design: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Lawrence Beare, Alan Nevill. Data analysis and interpretation: Alan Nevill, Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Lawrence Beare. Drafting article: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare, Alan Nevill. Critical revision of article: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare, Alan Nevill. Approval of article: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare, Alan Nevill. Statistics: Alan Nevill. Funding secured by: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley. Data collection: Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare. Project administration: Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Emma Sharman.


Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is now widely used in procedural sedation and analgesia. This study was designed to observe and compare the efficacy and safety of DEX administered in two different modes.In total, 100 patients were randomly divided into two groups to receive intravenous DEX 1 µg/kg over 15 min followed by 0.4–0.7 µg/kg/h infusion or DEX 1 µg/kg over 30 min followed by 0.4–0.7 µg/kg/h infusion. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), bispectral index (BIS), Ramsay Sedation Scores (RSS scores), the lowest respiratory rates (LRR), incidences of respiratory adverse events and frequencies of body movements were recorded. Recovery time, recall of intraoperative events, pain scores in PACU and satisfaction of patients and surgeons were assessed.p < 0.05). The RSS scores at time points from 5 min after anesthesia to immediately after induction with DEX were significantly higher in the intervention group (p < 0.05). The HR at time points from the beginning of surgery to 30 min after local anesthesia, the MAP at time points from 30 min after local anesthesia to the end of surgery, and the RR at time points from 5 min after anesthesia to the end of surgery were significantly higher in the intervention group (p < 0.05). Patients in the intervention group had higher LRR, lower incidences of respiratory adverse events, and shorter recovery time (p < 0.05).The BIS at time points from 5 min after anesthesia to the end of surgery in the intervention group were significantly higher (Dexmedetomidine infused with a loading dose over 30 min had less impact on patients’ hemodynamics and respiration and could shorten the recovery time after anesthesia in procedural sedation and analgesia.ClinicalTrials.gov, identifier: ChiCTR1900027958. Dexmedetomidine (DEX) has been used extensively in various superficial surgical procedures and sedation radiographic tests as it induces sedation, analgesia and anxiolysis without significant respiratory depression . DEX is Previous research reported that omitting the loading dose of DEX avoided hemodynamic side effects without compromising sedation and analgesia . No inven = 50) using a computer-generated list of random numbers. Exclusion criteria were: bradycardia (HR < 50 beat/min), hypotension , severe disease , obesity (Body mass index [BMI] ≥30), obstructive sleep apnea/hypopnea syndrome, and known allergy to DEX.This randomized controlled trial was approved by Ethic Committee of Plastic Surgery Hospital, Chinese Academy of Medical Science (2016–12) and registered in the Chinese clinical trial registry (ChiCTR1900027958). A total of 100 patients from December of 2019 to December of 2020, American Society of Anesthesiologists (ASA) physical status class I or II, aged 18–60 years, and scheduled for elective plastic surgery under procedural sedation and analgesia were enrolled in this trial. The patients were allocated randomly to one of the two groups (2) . Respiratory rate (RR) was monitored by a nasal end-tidal CO2 cannula. The bispectral index (BIS) was also continuously monitored . A peripheral intravenous (IV) catheter was inserted by nurse.No premedication was given to any of the patients. After being taken to the operating room, standard monitoring included electrocardiogram (ECG), noninvasive blood pressure (BP), HR and oxyhemoglobin saturation (SpOTable 1) and the BIS. The goal of sedation was to achieve an RSS of 3–5 or BIS of 60–80. Therefore, local anesthesia was performed. The patients’ MAP and HR were maintained at a range of baseline ±20%. Atropine (0.3 mg) and ephedrine (6 mg) were intravenously administered for bradycardia (HR < 50 beats/min for >60 s) and hypotension (MAP < 60 mmHg for >60 s), respectively. A facial oxygen mask (6 L/min) was used for hypoxia (SpO2 < 90%). If airway obstruction occurred, the patient was treated by thrusting the jaw. Midazolam (2 mg) was administered as a rescue drug when the infusion rate of DEX was increased to a maximum of 0.7 µg/kg/h and the depth of sedation was not achieved. The infusion of DEX was stopped 30 min before the end of surgery, and the infusion of remifentanil was turned off at the end of the surgery.All patients received an IV of midazolam (0.04 mg/kg) and a continuous infusion of remifentanil (0.1 µg/kg/min) at the beginning of anesthesia. Patients in the control group received IV DEX 1 µg/kg over 15 min followed by 0.4–0.7 µg/kg/h infusion and patients in the intervention group received IV DEX 1 µg/kg over 30 min followed by 0.4–0.7 µg/kg/h infusion. During the surgery, the level of sedation status was assessed using the Ramsay Sedation Scores (RSS)  (Table 10), 5 min after anesthesia (T1), 10 min after anesthesia (T2), immediately after induction with DEX (T3), the beginning of local anesthesia (T4), the beginning of surgery (T5), 30 min after local anesthesia (T6), 60 min after local anesthesia (T7), immediately after turning off DEX infusion (T8), and the end of surgery (T9). The lowest respiratory rates (LRR), incidences of respiratory depression (RR < 10 breaths/min), incidences of oxygen supplementation by facial mask and thrusting the jaw, frequencies of body movements, and additional rescue drug administrations were also recorded throughout the procedure. After surgery, recovery time, recall of intraoperative events, and pain scores using a numerical pain scale (0 = no pain to 10 = the worst pain) (Table 1).HR, MAP, RR, BIS, RSS were evaluated and recorded before anesthesia (baseline) . The normality of distribution was assessed with the Shapiro-Wilk test. Normally distributed data are presented as mean ± SD, and skewed data were presented as a median with an interquartile range [IQR]). Independent t-test was used to examine the difference of normally distributed continuous variables between groups. Skewed data were analyzed by Mann-Whitney U-test. Categorical data are presented by frequency and analyzed by chi-square test. A Figure 1). No significant differences were observed in patient demographic data including gender, age, ASA classification and BMI (Table 2). The surgery time did not differ between groups.The procedure was successfully performed in each of the 100 patients recruited in the study . Patients in the intervention group also had higher RSS scores compared with the control group at time points from 5 min after anesthesia to immediately after induction with DEX (p < 0.05).Figure 2B–D displays the hemodynamic and respiratory parameters changes during the study. Patients in the intervention group had higher HR at time points from the beginning of surgery to 30 min after local anesthesia, higher MAP at time points from 30 min after local anesthesia to the end of surgery, and higher RR at time points from 5 min after anesthesia to the end of surgery (p < 0.05).p < 0.05) (Table 4).Compared with the control group, patients in the intervention group had higher LRR, lower incidences of respiratory depression, lower incidences of oxygen supplementation by facial mask and thrusting the jaw, and a shorter recovery time (p > 0.05) (Table 4).No significant differences were found in body movements, additional rescue drug administrations, recall of intraoperative events, pain scores and the satisfaction levels of patients and surgeons between groups (Due to its numerous advantages, DEX is one of the main anesthetics currently used for procedural sedation and analgesia. In this study, we found that although DEX infused with a loading dose over 15 min provided deeper sedation than DEX infused with a loading dose over 30 min, these two different DEX administrations could both be effectively applied in the surgery. In addition, DEX infused with a loading dose over 30 min resulted in more stable hemodynamics, less respiratory depression, and shorted recovery time for patients in procedural sedative and analgesic anesthesia.In order to achieve satisfactory sedation and analgesia, DEX is often used clinically in combination with other anesthetic drugs such as midazolam and opioids –11. MidaWhile enhancing the anesthetic effect, the combination of sedation and analgesic drugs may also increase the incidences of respiratory and circulatory depressions. Clinically, the safety of anesthesia can be improved by reducing the dose of drugs or adjusting the method of drug administration , 15. In et al. (With respect to hemodynamic stability, Bloor et al.  reportedet al. , 19. We et al. , 21. We DEX is seldom administered in clinical practice as a single agent for procedural sedation and analgesia. It is often administered in combination with analgesics. Though DEX provides sedation and analgesia without significant respiratory depression, respiratory changes needed to be measured in the case of drug combinations . The depThere are a few limitations to this study. The method of DEX administration in the control group is extensively applied in clinical practice. Though higher respiratory depression was observed in this group, the problem could be solved by oxygen supplementation with facial mask or thrusting the jaw. Before the study, we excluded patients with known obesity or obstructive sleep apnea/hypopnea syndrome. For patients with a predictable risk of respiratory depression, further research is needed to identify the safety of this method of DEX administration.In conclusion, our study demonstrated that DEX is an excellent drug when combined with other narcotic drugs in sedative and analgesic anesthesia. Prolonging the DEX loading dose infusion time from 15 to 30 min can provide sufficient sedation during the surgery with more stable hemodynamics, as well as less respiratory adverse reactions.