Physical activity is an integral part of healthy aging; yet, most adults aged ≥65 years are not sufficiently active. Preliminary evidence suggests that web-based interventions with computer-tailored advice and Fitbit activity trackers may be well suited for older adults.Active for Life, a 12-week web-based physical activity intervention with 6 web-based modules of computer-tailored advice to increase physical activity in older Australians.The aim of this study was to examine the effectiveness of γ distribution and log link to compare MVPA and self-reported physical activity changes over time within each trial arm and between each of the trial arms.Participants were recruited both through the web and offline and were randomly assigned to 1 of 3 trial arms: tailoring+Fitbit, tailoring only, or a wait-list control. The computer-tailored advice was based on either participants’ Fitbit data (tailoring+Fitbit participants) or self-reported physical activity (tailoring-only participants). The main outcome was change in wrist-worn accelerometer (ActiGraph GT9X)–measured moderate to vigorous physical activity (MVPA) from baseline to after the intervention (week 12). The secondary outcomes were change in self-reported physical activity measured by means of the Active Australia Survey at the midintervention point (6 weeks), after the intervention (week 12), and at follow-up (week 24). Participants had a face-to-face meeting at baseline for a demonstration of the intervention and at baseline and week 12 to return the accelerometers. Generalized linear mixed model analyses were conducted with a P=.05). There were no significant within-group changes for MVPA over time in the tailoring+Fitbit group  or the tailoring-only group ; however, a significant decline was seen in the control group . The tailoring+Fitbit group participants increased their MVPA 59% (95% CI 6%-138%) more than those in the control group. A significant time by group interaction was observed for self-reported physical activity (P=.02). All groups increased their self-reported physical activity from baseline to week 6, week 12, and week 24, and this increase was greater in the tailoring+Fitbit group than in the control group at 6 weeks .A total of 243 participants were randomly assigned to tailoring+Fitbit , tailoring only , and wait-list control . Attrition was 28.8% (70/243) at 6 weeks, 31.7% (77/243) at 12 weeks, and 35.4% (86/243) at 24 weeks. No significant overall time by group interaction was observed for MVPA (A computer-tailored physical activity intervention with Fitbit integration resulted in improved MVPA outcomes in comparison with a control group in older adults.Australian New Zealand Clinical Trials Registry ACTRN12618000646246; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618000646246 Physical activity is important for healthy aging. Physical activity improves health and well-being and reduces the risk of chronic disease ,2. OlderWeb-based physical activity interventions are effective in young and middle-aged adults , and theTailored web-based interventions that provide automated personalized physical activity advice based on participants’ characteristics, physical activity, motivation, and environment are effective and may be particularly suited to older adults . This isTailored web-based interventions typically provide participants with personalized advice based on self-reported physical activity data; as such, it is possible that inaccurate advice is delivered because of overreporting of physical activity and social desirability bias . HoweverThe primary aim of the study was to test the effectiveness of a web-based computer-tailored physical activity intervention with Fitbit (Google LLC) integration at increasing objectively measured moderate to vigorous physical activity (MVPA) from before to after the intervention compared with a web-based computer-tailored physical activity intervention without Fitbit integration and a control group in adults aged ≥65 years. The secondary aims were to compare the web-based computer-tailored intervention with and without Fitbit integration and the control group on objectively measured sedentary behavior from before to after the intervention and to compare subjectively measured physical activity and sitting time changes at the midintervention point, after the intervention, and at follow-up.We hypothesized that the web-based computer-tailored physical activity intervention with Fitbit integration would lead to increased objectively measured MVPA and self-reported physical activity over time and decreased objectively measured sedentary behavior and self-reported sitting time over time compared with the web-based computer-tailored physical activity intervention without Fitbit integration and a control group.A 3-arm randomized controlled trial was conducted where participants were randomized into one of three groups: (1) tailoring+Fitbit, (2) tailored advice only, and (3) wait-list control. Participants completed web-based surveys at baseline (week 0), at the midintervention point (week 6), after the intervention (week 12), and at follow-up (week 24). Objective physical activity and sedentary behavior were collected by means of wrist-worn accelerometry at baseline and week 12. More detail of the methods can be found in a protocol paper of the trial .Participants were recruited in Rockhampton , Bundaberg , and Adelaide , Australia, through paid Facebook advertising, email lists, flyers, and local newsletters. Recruitment was carried out between April 2018 and March 2019, and data collection was completed in November 2019. Eligible participants were English-speaking adults aged ≥65 years who had internet access and basic internet confidence, could attend 2 face-to-face appointments at one of the project locations, and could safely increase their physical activity as determined by the Physical Activity Readiness Questionnaire  or generα at .05. The decision to end participant recruitment was made by the lead (SJA) and senior (CV) investigators because the trial was close to the sample size goal (n=243), the remaining funds were limited, and interest in the trial had slowed.To detect differences between the 2 intervention groups and the control group for accelerometer-measured MVPA from baseline to after the intervention, 100 participants per group were required. This was to detect an effect size of 0.37 based on the average effect size of web-based physical activity interventions for inactive adults . This acActive for Life intervention website and Fitbit participants were provided with a Fitbit activity tracker and shown how to sync it to the intervention website. After the 12-week intervention, participants attended another face-to-face follow-up appointment to return the week 12 accelerometer. Participants received up to 3 email reminders for each research survey. If the surveys were still incomplete after the reminders, participants were offered a voucher worth Aus $20 (US $15) to complete them within the next few days. Participants received a voucher worth Aus $50 (US $37) after completing all research surveys. Wait-list participants were given access to the intervention after completing the week 24 research survey.Advertising materials directed prospective participants to the landing page of the intervention website, which had more details about study participation and access to the participant information sheet and eligibility survey. Prospective participants were automatically notified of their eligibility upon completion of the survey, and eligible participants received a welcome email. Participants were asked to complete web-based research surveys at baseline, week 6, week 12, and week 24 through the intervention website. Participants indicated their informed consent through a check box at the beginning of the baseline survey. If participants missed a survey, they were still asked to complete later surveys. Participants were posted an accelerometer to wear on their wrist for 7 consecutive 24-hour days, including when sleeping and showering, at baseline and week 12. The blinded accelerometers were only used for research evaluation and were not part of the intervention. Participants attended a baseline appointment to return the baseline accelerometer and were randomly allocated to one of the three trial arms . Randomization lists were created by the lead investigator (SJA) using computer-automated block randomization with block sizes of 15 and a 1:1:1 ratio. Randomization was stratified by sex  and age (<75 years and >75 years) to ensure an equal distribution of men and women in different age groups over the intervention arms. Using the randomization lists, the research manager (DP) and research assistants (CW and NW) assigned the participants by date of baseline appointment. Because of the nature of the intervention, neither the researchers nor the participants were blinded to group allocation. During the appointment, after randomization, intervention group participants were shown through the Active for Life intervention is a 12-week web-based program with 6 modules of tailored advice delivered biweekly. The modules of tailored advice are computer automated and use participant data to select appropriate messages from a database of messages using if-then algorithms . The advice is based on the theory of planned behavior [Are you meeting the guidelines?, Losing weight, and Exercise with arthritis). Some sections include a graph or a picture  for being active in the following fortnight. The intervention website also includes an exercise library where participants can access strength and flexibility exercise plans, written by a physiotherapist, suitable for the beginner and intermediate levels. The plans are 4 weeks in duration, and participants can view videos of the exercises through a link to an external website (Physitrack PLC).Both the tailoring+Fitbit and the tailoring-only participants were given access to the same intervention, including the 6 modules of computer-tailored advice, action-planning tool, and exercise library. Both groups completed a brief questionnaire at the start of each module to inform the computer-tailored advice. The only difference was that the tailoring+Fitbit participants were required to sync their Fitbit activity tracker with the website to measure their physical activity over the past 2 weeks, whereas the tailoring-only group answered a few additional questions that asked them to recall how many minutes of physical activity they had completed in the past 2 weeks. All other questions  were identical. Participants in the control group initially only received access to the research surveys, but after completing the week 24 survey, they also received access to the tailored advice modules, action-planning tool, and exercise library.Objective measurement of physical activity and sedentary behavior was carried out by means of wrist-worn ActiGraph GT9X accelerometers at baseline and week 12. Accelerations were recorded at 30 Hz. Accelerometer data were processed through ActiLife and valid wear time was set at 16 hours each day on a minimum of 5 days. Nonwear time was assessed based on vector magnitude using the Choi et al  algorithr=0.35) in older adults [Physical activity was also assessed in all groups at baseline, week 6, week 12, and week 24 by means of the Active Australia Survey , which mr adults .r=0.22-0.46, men: r=0.18-0.29) for both work and nonwork days [Sitting time was assessed at baseline, week 6, week 12, and week 24 by means of the Workforce Sitting Questionnaire . The queork days .strongly agree) to 1 (strongly disagree). Items are added together to produce a summary score; higher scores indicate higher internet self-efficacy.Participant demographics, including sex, age, marital status (single or married or de facto relationship), height and weight , English as main language (yes or no), education level , employment , pretax household income , and current health diagnosis (yes or no) were measured at baseline. Internet self-efficacy as assessed by means of the valid and reliable Internet Self-efficacy Scale was also assessed at baseline . The Intγ distribution with log link was used for the analyses on accelerometer-measured MVPA and self-reported physical activity because of positively skewed distributions. A normal distribution with identity link was used for the analyses on accelerometer-measured sedentary behavior and self-reported sitting time. Group  by time (baseline and week 12) interactions on accelerometer-measured MVPA and sedentary behavior were analyzed. These analyses controlled for accelerometer wear time. Group  by time  interactions on self-reported physical activity and sitting time were analyzed. A sensitivity analysis was conducted to determine the effect of missing data on analysis outcomes. Under the assumption of missing at random, missing values were imputed through chained equations. The fully conditional specification was used to create 20 imputed data sets that were used to conduct the sensitivity analysis. Analyses were conducted using SAS  with an α of .05.Analyses of primary and secondary outcomes followed the intention-to-treat principle. Separate generalized linear mixed model analyses were conducted to test the primary outcome of changes in accelerometer-measured MVPA by group and to test the secondary outcomes of changes in self-reported physical activity, accelerometer-measured sedentary behavior, and self-reported sitting time by group. A Ethics approval was received from the Central Queensland University Human Ethics Committee before data collection commenced (H16/12-321).2 (overweight), and the average internet self-efficacy was good at 44 (SD 47.00) out of 56 [2) than participants who did not . No other differences were observed for demographics, health, or internet use between participants who completed the week 12 outcomes and those who did not.ut of 56 . ParticiP=.05). No significant improvements in accelerometer-measured MVPA were observed from baseline to after the intervention within any group; however, the control group participants significantly decreased their MVPA by 35%. A pairwise difference was observed between the tailoring+Fitbit group and the control group, where the tailoring+Fitbit group participants increased their MVPA between baseline and week 12 by 59% more than those in the control group. This effect remained in the sensitivity analysis; however, the magnitude was reduced (43% difference). An overall time by group interaction was observed for self-reported total physical activity. All groups increased their self-reported physical activity from baseline to week 6, week 12, and week 24, and pairwise group comparisons revealed that this increase was 61% greater in the tailoring+Fitbit group than in the control group at 6 weeks. The effect was smaller in the sensitivity analysis (34% difference) and did not meet the criterion for significance.No overall time by group interaction was observed for accelerometer-measured sedentary behavior. The tailoring+Fitbit and control groups significantly increased their accelerometer-measured sedentary behavior from baseline to after the intervention . The magnitude of these effects was lower in the sensitivity analysis  and did not meet the criterion for significance in the tailoring+Fitbit group. No pairwise group differences were observed. No overall time by group interaction was observed for self-reported sitting time. The tailoring+Fitbit group participants decreased their self-reported sitting time between baseline and week 6, 12, and 24 . The tailoring-only group participants decreased their self-reported sitting time between baseline and week 6 and 24 . These effects remained in the sensitivity analysis; however, the magnitudes were reduced. Pairwise group comparisons revealed that the tailoring+Fitbit group participants decreased their sitting time between baseline and after the intervention 133 minutes per day more than those in the control group. However, the magnitude of effect was lower in the sensitivity analysis (98-minute decrease per day) and did not meet the criterion for significance.The main aim of the study was to determine the effectiveness of a computer-tailored physical activity intervention with Fitbit integration compared with a tailoring-only group and a control group at increasing MVPA from before to after the intervention. The second aim was to determine the effectiveness of a computer-tailored physical activity intervention with Fitbit integration compared with a tailoring-only group and a control group at increasing self-reported physical activity from before the intervention to the midintervention point, after the intervention, and follow-up. The findings showed that there were no significant MVPA changes in the tailoring+Fitbit group or tailoring-only group, whereas there was a decrease in the MVPA of the control group. MVPA increased more in the tailoring+Fitbit group than in the control group. All groups reported increasing their self-reported physical activity, and this increase was greater in the tailoring+Fitbit group than in the control group at the midintervention point. Together, these findings support past studies that have demonstrated that face-to-face, telephone, SMS text messaging, and email physical activity interventions using activity trackers are effective in older adults compared with a control group -27. MostThe effectiveness of the tailoring+Fitbit intervention compared with a control group may be further improved by increasing the frequency of the feedback provided. Larsen et al  conducteThis study found no significant difference in accelerometer-measured MVPA or self-reported physical activity in the tailoring+Fitbit group compared with the tailoring-only group. This is not consistent with the findings of Vandelanotte et al , who fouThis study did not observe a difference in self-reported physical activity or accelerometer-measured MVPA over time between the tailoring-only and control groups. Previous research has demonstrated the overall effectiveness of computer-tailored physical activity advice in middle-aged adults , but theThe increase in objectively measured sedentary behavior in the tailoring+Fitbit group is not in line with a meta-analysis that found no intervention effect on sedentary behavior outcomes for either interventions targeting physical activity alone or those targeting both physical activity and sedentary behavior . HoweverThe strengths of this study include the 3-group randomized design to determine individual effects of a tailored web-based physical activity intervention with and without Fitbit integration compared with a wait-list control group. The study objectively assessed physical activity at baseline and after the intervention. Although attrition at week 12 was moderate , this is comparable to many other trials examining web-based interventions -52. AlthIn conclusion, computer-tailored advice based on Fitbit measurement of physical activity in older adults is likely to lead to improved physical activity outcomes compared with no advice but not compared with advice based on self-reported physical activity. More research is needed to investigate ways to further improve effectiveness of computer-tailored advice based on Fitbit measurement in older adults.


Textured breast implants have been used in aesthetic breast surgery to decrease rates of malposition and capsular contracture. Recent concerns regarding breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)’s link to textured devices have prompted many physicians to reevaluate their use.The authors aimed to create an algorithm for when to use smooth vs micro-textured breast implants and provide their rationale for when micro-textured implants may be more beneficial.In total, 133 patients received primary augmentations performed by a single surgeon from January 2018 to December 2020; 84 patients received smooth implants and 49 patients received micro-textured implants. All surgeries were performed in the dual plane using an inframammary incision. Implant-related complications and scar malposition were recorded and compared between groups.P-value 0.621257; 95% CI −0.06100 to 0.007467]). There were no cases of BIA-ALCL. A comparison of scar malposition rates between the smooth and micro-textured groups also revealed no statistically significant difference . Patients in the micro-textured group proportionately had more anatomical risk factors for malposition.No significant difference in the prevalence of implant-related complications was found (3.57% for smooth devices and 2.04% for micro-textured devices [Micro-textured breast implants continue to be a safe and effective choice for patients. Micro-textured implants show a trend toward decreased scar malposition, although not statistically significant. Patients at high risk for malposition with micro-textured breast implants give similar results to patients at average risk for malposition with smooth implants. The scrutiny led to the FDA’s 2019 request to Allergan  to voluntarily recall their line of Biocell  macro-textured breast implants in the United States; locally, many surgeons have discontinued their use of textured implants, and globally there are discussions about the safety of textured breast implants.Modern plastic surgery no longer relies on a cookie-cutter approach to breast augmentation. Plastic surgeons now have a multitude of implant options available to them to customize results while considering each patient’s breast anatomy, desired aesthetic results, and available options. Given the pros and cons of available implants, the authors have compiled their rationale for when the use of micro-textured silicone gel breast implants may be more beneficial.A cohort analysis was conducted using data collected from 133 primary augmentation mammaplasty cases performed between January 2018 and December 2020. All surgeries were performed by the senior author (S.S.K.) and were consecutive patients. A total of 133 surgeries were performed with bilateral silicone gel breast implants, of which 84 cases utilized smooth breast implants and 49 cases utilized micro-textured breast implants. All patients were female, ranging from ages 18 to 64 years (mean patients age in this study was 32 years). Implant surface (micro-textured or smooth) and shape  were selected for each patient at a consultation or preoperative appointment according to SSK’s Breast Augmentation Implant Selection Algorithm  based on7 Intravenous antibiotics were administered to patients at the start of the anesthetic . All patients in the study received an inframammary incision for dual-plane breast augmentation. Careful atraumatic dissection with electrocautery was performed to have a bloodless field. Pocket irrigation was performed in all cases, with the preferred irrigation being a triple antibiotic solution containing Cefazolin, Bacitracin, and Gentamicin,8 except when patients had an allergy or if supplies of ingredients for the triple antibiotic were unavailable, in those situations.In all breast implant cases, techniques to reduce the risk of bacterial contamination of the breast implants during surgery were employed.PhaseOne  hypochlorous acid (HOCl) or 50% betadine solution was used. The use of an introduction sleeve, new gloves before handling the implants, and careful attention to sterile technique were all employed to minimize the bacterial burden. Three-layered suture closure was used for all cases. Drains were never used. Postoperative antibiotic prophylaxis was employed, with all patients receiving a cephalosporin antibiotic  for 10 days except in the case of a known allergy.Patients were monitored from the time of implant placement with the typical in-person follow-up schedule of 1 week post-surgery, 1 month post-surgery, 3 months post-surgery, 6 months post-surgery, and yearly follow-up appointments for each subsequent anniversary. Patient photographs were reviewed at minimum 2 months follow-up and beyond, and an assessment was made of the patient’s outcomes from their latest available follow-up at the time of the study. Complications related to breast implants including skin infection, wound dehiscence, hematoma, seroma, capsular contracture (Baker Grade III-IV), and need for reoperation were recorded. Implant malposition was also gauged by comparing inframammary scar migration in postoperative appointment photographs.t-tests, and 95% CIs were constructed.The average length of follow-up for each group’s scar assessment was comparable to left-skewed distributions: 7.4 months for the smooth group and 8.2 months for the micro-textured group. For both groups, the mean follow-up was less than a year, and the maximum follow-up was 2 years. Measurements were taken on a computer by a single independent evaluator from the scar position to the visible inframammary crease in photographs. This was used as a gauge of displacement because all incisions were made directly in the inframammary crease during surgery and were secured there upon closure. A study scale was developed to classify scar malposition into 3 categories : minor . The scaled complication rate for the smooth group was 3.57% (3) compared with 2.04% (1) for the micro-textured group . The micro-textured cohort demonstrated a reduced severity of scar malposition when it did occur, with a higher proportion of its malposition cases classified as minor compared with the smooth implant group. The textured implant group had no cases of major scar malposition and only one case of moderate scar malposition.The mean follow-up time period was 9.3 months (SD 1.23) for the smooth devices alone cohort, and 8.6 months (SD 1.04) for the micro-textured devices cohort. No significant difference in the prevalence of implant-related complications was found between the smooth and micro-textured groups  and has been linked to higher rates of double capsule formation, late seroma, and BIA-ALCL. A significant reduction in scar malposition rates may have been observed if implants with a higher grade of texture had been used, but the authors chose to use only micro-textured implants due to safety considerations given the existing data on these shells.This study found no significant difference in the prevalence of clinically significant malposition between the smooth and micro-textured implant groups. This was contrary to the expected result of a decreased rate of malposition for the textured subset; it is possible with a larger sample size that a statistical benefit of micro-textured implants could have been seen. Additionally, this study utilized only micro-textured implants as these are the only textured devices available in the US market. Due to data showing higher incidence of double capsule formation and BIA-ALCL linked to Allergan’s macro-textured Biocell implants,16 This resistance to movement is the main implant selection consideration when choosing between smooth and micro-textured implants for individual patients17-19  as the senior author tended to use Allergan implants exclusively for larger implant sizes not available by Sientra. Larger breast implants have been found to be more likely to develop malposition or ptosis due to their greater mass placing strain on the pocket over time.20 Thus, the authors concluded that this difference was likely not due to a true distinction in the clinical performance of the 2 brands’ smooth implant surfaces, but rather the trend in implant size selected by the patients.With deeper analysis, the smooth implant group trended toward a slightly higher rate of scar malposition in patients who received Allergan’s Natrelle Inspira SoftTouch Smooth Round Gel implants (17.3%) compared with the patients who received Sientra’s HSC + Opus Luxe Smooth implants (12.9%), though this difference was not statistically significant. Of note, patients who were selected to receive Allergan smooth round implants tended to be opting for larger implants (average volume = 458 mL) compared with the patients selected to receive Sientra smooth round implants (average volume = 402 mL); this was a statistically significant difference , and the opportunity to ask the surgeon questions about capsular contracture, BIA-ALCL, and any other potential complications associated with a primary breast augmentation.21. One current theory for this correlation is that the texture of the implant surface causes degradation of the contracted capsule that is beneficial to preventing advanced capsular contracture, while another theory posits that the breast tissue grows into the texture and increases friction over a greater surface area, which reduces synovial-type metaplasia observed in the capsules formed around smooth breast implants and disrupts the planar arrangement of fibroblasts, altering the vectors of contraction.21-23 A variety of risk factors for capsular contracture in addition to the use of smooth implants have also been identified, including subglandular placement, the use of a periareolar incision, device size (<355 mL), and surgical bra usage.24Decreased incidence of Baker grades III and IV capsular contracture with textured shells has been observed, though some studies exist to contradict the relationship between texture and decreased capsular contracture10 The elimination of the option for board-certified plastic surgeons to utilize micro-textured implants in proper applications would undermine the goal of providing the best outcomes to patients with each individual’s unique history and risk factors properly weighted and taken into account.BIA-ALCL would be a tragic sequela of an elective procedure; however, there are also numerous risks associated with reoperation necessitated by the incidence of major implant malposition or capsular contracture. Regimented follow-up with the patient post-surgery can allow for a quick evaluation and treatment of any sudden expansion or pain that may be associated with a possible complication related to a textured breast implant. Case studies of BIA-ALCL show that it is treatable when detected early, with most cases treated by total capsulectomy yielding a favorable prognosis.26 While both capsular contracture and BIA-ALCL are linked with bacterial contamination, Gram-positive bacteria are associated with capsular contracture, whereas Gram-negative bacteria are associated with BIA-ALCL cases.27 The current hypothesized reason for this difference is that Gram-positive bacteria provide a pathway toward inflammation and fibrosis, leading to capsular contracture, whereas Gram-negative bacteria trigger lymphocyte stimulation.13 Thus, the current approach to minimizing the risk of BIA-ALCL is reducing Gram-negative bacterial burden through pocket irrigation with antibiotics.While the textured shell may provide a protective effect against capsular contracture, they pose a small risk of BIA-ALCL compared with no risk with the use of smooth implants. Current theories for cancer’s pathogenesis include a possible immune reaction to the silicone of the implant or inflammation caused by the surface texture, with the higher surface area of macro-textured implants providing a larger area available for bacterial growth and subsequent inflammatory response.This study cohort was small and took place over less than 2 years and thus did not record any cases of BIA-ALCL or capsular contracture as these conditions typically take years to develop. The main purpose of this study was to evaluate micro-texture’s protective benefit against implant malposition rather than investigate the development of these implant-related complications. Taking into account the current literature defining the risk level of BIA-ALCL with micro-textured implants, the authors believe that their results provide a rationale for the standard use of smooth implants whenever anatomy permits; however, the use of micro-textured implants in more complex augmentations  may present benefits that outweigh the relative risk of BIA-ALCL, such as a reduced risk of reoperation.In patients where a similar aesthetic and functional outcome could be achieved using round smooth silicone gel breast implants, the senior author always opted to use the smooth shell unless a micro-textured breast implant was requested by the patient. Reasons cited by patients for requesting a micro-textured implant included more durable and long-lasting results through better pocket control , 7. Case28As can be seen, the majority of devices implanted by the senior author were smooth-surfaced implants, because, in a majority of situations, a smooth device can probably yield an equivalent outcome to a textured device with less risk for anaplastic large cell lymphoma; however, the option of a micro-textured implant for select patients was an important tool for meeting individual patient needs. The authors also believe that adherence to a frequent follow-up schedule with all patients, regardless of the implant surface, is crucial in maintaining patient safety so that the development of implant-related complications may be caught early. The patients in this cohort were seen according to the regular follow-up schedule previously described and, after this remedial period, are monitored lifelong with the exception of patients lost to follow-up. Ultimately, the authors believe that this minimizes the risk of using micro-textured implants in qualifying patients. Future studies looking at greater control with internal support matrices may be considered as alternatives to micro-textured implants.A board-certified plastic surgeon has greater tools in their armamentarium in the modern era—this comes with a responsibility to understand and maintain the proper usage of these techniques and options. There is a balance to be struck between meeting patient expectations and achieving durable and safe outcomes. We believe that, with proper surgical technique, patient counseling, and implant selection, the micro-textured implants can still be safely used in modern breast augmentation surgery and should be maintained as an option for board-certified plastic surgeons in order to provide individualized results on a patient-by-patient basis.


Dispersion management plays an important role in improving the output performance of a mode-locked fiber laser. Therefore, dispersion management is carried out by introducing the grating pair in our experiment. Through adjusting the distance between the grating pair, mode-locked pulses corresponding to different dispersion regimes can be realized, which typically range from soliton state in the anomalous dispersion regime to the dissipative soliton format in the normal dispersion regime. Furthermore, tunable spectrum distribution can be achieved by adjusting two intra-cavity polarization controllers. The proposed dispersion management method complements mode-locking techniques based on nonlinear multimode interference (NL-MMI). The laser can operate with self-start mode locking stably and is useful for practice applications. Ultrafast fiber lasers have been developed rapidly in the fields of science, industry and healthcare because of their compactness and efficiency ,2. Due tIn all-normal-dispersion (1 μm waveband) ,26,27,28In this work, dispersion management is carried out by introducing the grating pair. The different mode-locked states ranging from soliton state in anomalous dispersion to dissipative soliton format in the normal dispersion regime have been realized experimentally. Furthermore, tunable spectrum distribution can be achieved by adjusting two intra-cavity PCs. The proposed dispersion management method complements mode-locking techniques based on MMI.The experiment scheme of the Yb-doped fiber laser is presented in 00 mode in the GIMF to that of the fundamental mode in the SMF, so that the transmission of laser in SMF-SIMF-GIMF-SMF structure does not depend on the length of the GIMF. The SIMF has a 105 μm core diameter and GIMF has a 50 μm core diameter. The nonlinear transmittance properties of SA are measured by a, centered at 1030 nm, ultrashort pulse fiber laser with 10 ps pulse duration at 45 MHz repetition rates. The experimental values are fitted by the following formula: Theoretically, achieving a mode-locking operation can only be done by controlling the length of the GIMF (L) to exact values , but this is difficult to be precise in practice. In the experiment, we can increase the number of higher-order modes by adding a 0.5 m SIMF segment between SMF and GIMF. Bending SIMF can change the ratio of the mode field diameter of the LG2. The fundamental mode-locking operation can be obtained with the pump power of 914 mW and two appropriate PC adjustments. The characteristics of the traditional soliton are shown in We study the ytterbium-doped passively mode-locked fiber laser with a distance between the grating pair of 50 mm, which corresponds to the net dispersion in the cavity of −0.18472 psWe compare the output performance of dispersion management Yb-doped mode-locked fiber laser proposed with that of other researchers using NL-MMI as SA from the aspects of center wavelength, 3 dB bandwidth, modulation depth, pulse width, repetition rate and output power, as shown in 2 from −0.15252 ps2 when the orientations of two PCs are maintained. In In addition to the experimental study discussed above, we also studied the influence of intra-cavity net dispersion on NL-MMI mode-locked fiber laser. With the distance between the grating pair decreasing, the intra-cavity net dispersion can reach 0.0439 ps2 fit. Furthermore, the 3 dB bandwidth of tunable spectrum can be achieved from 15.7 to 17 nm with a distance between the grating pair of 14.5 mm and two appropriate PC adjustments. In In conclusion, dispersion management was carried out by introducing the grating pair in our experiment and we successfully studied the effect of dispersion on the performance of the laser. By slowly adjusting the distance between the grating pair, the different mode-locked states ranging from soliton state in the anomalous dispersion regime to the dissipative soliton format in the normal dispersion regime have been realized experimentally. Furthermore, we also realized that the 3 dB bandwidth of tunable spectrum from 15.7 to 17 nm by slightly adjusting two intra-cavity PCs. The ytterbium-doped fiber laser with dispersion management can operate with self-start mode locking stably and is useful for practice applications.


Salmonella enterica is capable of invading different host cell types including epithelial cells and M cells during local infection, and immune cells and fibroblasts during the subsequent systemic spread. The intracellular lifestyles of Salmonella inside different cell types are remarkable for their distinct residential niches, and their varying replication rates. To study this, researchers have employed different cell models, such as various epithelial cells, immune cells, and fibroblasts. In epithelial cells, S. Typhimurium dwells within modified endolysosomes or gains access to the host cytoplasm. In the cytoplasm, the pathogen is exposed to the host autophagy machinery or poised for rapid multiplication, whereas it grows at a slower rate or remains dormant within the endomembrane-bound compartments. The swift bimodal lifestyle is not observed in fibroblasts and immune cells, and it emerges that these cells handle intracellular S. Typhimurium through different clearance machineries. Moreover, in these cell types S. Typhimurium grows withing modified phagosomes of distinct functional composition by adopting targeted molecular countermeasures. The preference for one or the other intracellular niche and the diverse cell type-specific Salmonella lifestyles are determined by the complex interactions between a myriad of bacterial effectors and host factors. It is important to understand how this communication is differentially regulated dependent on the host cell type and on the distinct intracellular growth rate. To support the efforts in deciphering Salmonella invasion across the different infection models, we provide a systematic comparison of the findings yielded from cell culture models. We also outline the future directions towards a better understanding of these differential Salmonella intracellular lifestyles. Salmonella enterica subsp. enterica that includes both typhoidal and non-typhoidal Salmonella (NTS) serovars. Infection leads to different symptoms encompassing enteric fever, self-limiting gastroenteritis, septicemia, focal infections and, in the case of some typhoidal strains, an asymptomatic carrier state. NTS-caused gastroenteritis is generally self-resolving in healthy adults, but it can also cause systemic infection in immunosuppressed humans as well as very young and older individuals. Salmonella pathogenicity has been mostly studied by using Salmonella enterica serovar Typhimurium (hereafter referred as S. Typhimurium). It starts in the intestine, and then it can spread to other organs, such as the spleen or liver. A hallmark of this pathogen is its capacity to actively induce its internalization in a wide range of host cells and avoiding destruction by professional phagocytic cells. The interaction with the different host cells leads to the formation of specific intracellular niches with diverse growth rates and clearance efficacies , Caco-2 , HT-29 , T84 (colon carcinoma from lung metastasis) and MDCK (transformed dog kidney cells). The above-mentioned cell lines are selected as model systems based on two primary criteria: the representation of key biological features during an infection and the compatibility towards the experimental setup and procedures  and its injecting bacterial effectors   within epithelial cells. Formation of spacious vacuole-associated tubules (SVATs) shrinks the SCV while the fusion with macropinosomes increases its size  . Passivent (SCC) . The SCCits size . These tS. Typhimurium shifts gears from the expression of Salmonella Pathogenicity Island (SPI)-1 encoded genes to the expression of SPI-2 encoded genes. This transcriptional reprogramming changes the bacterial physiology from the invasion mode into that of intracellular niche formation through the SPI-2 encoded T3SS-2 bacterial effectors , a highly dynamic membrane network that extends and helps maintaining a replicative niche by allowing vacuolar bacteria to access nutrients from endocytosed material  pathway that subsequently restricts the S. Typhimurium growth  that recruits caspase-4 to the bacterial surface , mouse 3T3-Swiss albino fibroblasts (3T3 fibroblast), normal rat kidney fibroblasts (NRK-49F) and immortalized human foreskin fibroblasts (BJ-5ta) . The non-replicative Salmonellae are also linked to the differential secretion of a set of expressed T3SS-2 effectors that potentially modulates the bacterial dissociation from the aggresome , immortalized BMDMs, THP-1 and human monocyte-derived macrophages (hMDMs)  and M2-activated macrophages, while M1-activated cells killed intracellular S. Typhimurium  . RAW264. (hMDMs) . The BMDhimurium . A more t manner . THP-1 iSalmonella-susceptible professional immune cells are phagocytic, which enables dual entry routes of the pathogen through active or passive machineries. This contrasts with the interaction of S. Typhimurium with the epithelial cells or fibroblasts. First, S. Typhimurium can passively enter the macrophage simply by being phagocytosed within a phagosome. Second, S. Typhimurium can also actively enter macrophages by injecting the T3SS-1 effectors, which induces membrane ruffling and bacterial uptake that morphologically resembles the uptake within epithelial cells and fibroblasts. S. Typhimurium entering through the action of the T3SS-1 machinery is localized in a host endocytic compartment expected to have a distinct identity and composition from the phagosome containing passively engulfed bacteria. Drecktrah et al. have described the distinct features of the two routes of entry, including the modes of intracellular survival, SCV maturation, as well as the virulence gene expression from SPI-1 and SPI-2  cascade. It was found that the SPI-2 bacterial effectors SseK1 and SseK3 inhibit the MLKL-mediated cell death through GlcNAcylation of different host proteins to counteract the host defense . It was found that the pyroptotic corpses trap the S. Typhimurium within the cell remnants without killing and recruit the neutrophils for cell corpse clearance . Even mText Box 1S. Typhimurium interactions with the host. However, both of them cannot be linked easily to provide a satisfactory and comprehensive physiological representation, while remaining accessible for experimental interventions. Desirable intermediate models bridging the cellular scale with tissue and full body scale are not only demanded by academic scientists to close our knowledge gap, but also by the pharmaceutical industry to obtain more reliable drug screening data prior to later phases of animal and clinical trials.Recently, biologists and bioengineers have harnessed the knowledge in multicellular tissue culture and advanced micro-fabrication techniques to establish in vitro models that better recapitulate the in vivo environment, including the cellular micro-environment, biomechanical forces and multicellular interactions. Dwelling in endogenous tissues, cells are subjected to different degrees of cell constraints as compared to unconstrained cells grown on plates, which alters cellular physiology, including interactions between the host cell and S. Typhimurium  International PhD Program. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 665807. CHL is a recipient of the Doctoral Fellowship from the Croucher Foundation and 4th year Doctoral Award from Fondation pour la Recherche Médicale. JE acknowledges the support from the European Union (ERC-CG-grant: EndoSubvert), and the ANR (program: HBPSensing and PureMagRupture). JE is part of the IBEID and the Milieu Interieur LabExes.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


While the global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still ongoing and new virus variants are emerging, there is a universal need for vaccines to protect individuals from severe complications and ideally control the pandemic by enabling herd immunity. Several vaccines against SARS-CoV-2 have been approved and are widely used to stem the recurring waves of coronavirus disease 2019 (COVID-19). Post-marketing surveillance is essential to record even rare safety issues related to these new vaccines. Among these issues, several autoimmune phenomena have been recorded in temporal association with and feasibly triggered by a vaccination. Acquired haemophilia A (AHA) is a rare condition characterized by new-onset haemorrhagic diathesis caused by an inhibitor of blood clotting factor VIII (FVIII), often in the elderly and most commonly associated with autoimmune or malignant disease. There have been a small number of AHA cases triggered by vaccinations, including those against SARS-CoV-2. We report the first case of AHA in temporal association with an mRNA-1273 booster vaccination. The diagnosis was made promptly, and the patient received appropriate care including immunosuppression using glucocorticoids, cyclophosphamide (CYC) and rituximab (RTX). The haemorrhage ceased after escalation of treatment, and the patient is recovering. Concurrent malignancy was initially ruled out using a wide scope of diagnostic tests, but pleomorphic dermal sarcoma (PDS) of the forehead occurred after initiation of specific AHA immunosuppressive treatment. Since large vaccination programs are ongoing worldwide and potential adverse events during post-marketing surveillance have been reported following vaccination against SARS-CoV-2, this case illustrates challenges in rare events occurring in association with SARS-CoV-2 vaccination and to proof a causal relationship. Therefore, there is an urgent need for reporting any events in association with SARS-CoV-2 vaccination, but also a crucial discussion about possible concurrent triggers and follow-up information about individual patients. As the coronavirus pandemic is ongoing and new variants of SARS-CoV-2 emerge, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity , 2. The 3/µL, normal range: 150-500×103/µL) and leukocyte counts . The coagulation profile revealed a normal international normalized ratio (INR) of 0.9 , but a distinctly prolonged aPTT of 164.6 seconds . Both fibrinogen  and antithrombin III  were within normal limits. The patient was transfused two units of packed red cells (PRC) and then admitted to the intermediate care ward (IMC) at our tertiary centre for further treatment of what was suspected to be AHA. Upon admission, the complete blood count confirmed anaemia  with normal platelets and leukocyte counts. A differential blood count showed normal distribution of lymphocytes , monocytes , eosinophils , basophils  and neutrophils  and carpal tunnel syndrome, a 50 pack-year smoking history, and no documented history of COVID-19 received homologous BNT162b2 vaccinations (05/2021 and 06/2021) and an mRNA-1273 booster vaccination against SARS-CoV-2 (12/2021). The patient had no allergies, no history of immune deficiency, no recent infections or fevers, and no personal or family history of any bleeding disorders. Nine days after mRNA-1273 booster vaccination, the patient started to notice several bruises appearing on his arms, left leg and trunk (2) on day 27 (The patient was started on recombinant activated FVII (rFVIIa) and received oral prednisone (100 mg per day) as per the recommendations of the German Society for Thrombosis and Haemostasis Research (GTH) and international treatment guidelines , 8. A prThe patient underwent further diagnostic testing in order to rule out active malignancy as another potential trigger for AHA. In view of the past medical history of BPH, prostate-specific antigen was measured, which was within normal limits  and hence gave no indication of prostatic cancer. A CT scan of the neck, chest, abdomen and pelvis was performed, which yielded a 4 cm mass on the left adrenal gland as the sole pathological finding. A dedicated adrenal CT with arterial and portalvenous contrast phase confirmed the mass to be a lipid adenoma. An MRI of the cranium was completed and showed no evidence of an intracranial lesion. During the further hospital stay, a small nodule (1 cm in diameter) was discovered on the patient’s forehead. A punch biopsy revealed a pleomorphic dermal sarcoma (PDS), and the patient was presented to the multidisciplinary tumour board at our tertiary centre. Surgical excision was recommended. The patient did present to the surgical clinic earlier than scheduled and described a now rapidly growing nodule on his forehead, so that the date of surgery had to be expedited with complete resection. In summary, we herein present the course of a patient with AHA in close temporal association with both, mRNA-1273 booster vaccination against SARS-CoV-2 as well as the diagnosis of a PDS. The case was reported to the Federal Institute for Vaccines and Biomedicines (Paul-Ehrlich-Institute). According to current recommendations, the patient will be followed-up after complete remission, monitoring FVIII activity monthly during the first 6 months, every 2-3 months up to 12 months, and every 6 months during the second year and beyond .2) in a slightly accelerated version of the current recommendations of the German Society of Thrombosis and Haemostasis Research (GTH). The algorithm of the GTH working group on AHA suggests corticosteroid treatment for three weeks or until partial remission (PR) is achieved, which is defined as FVIII activity >50% without blood products and with no active bleeding. If PR is not achieved, the guidelines recommend CYC (week 4-6) followed by RTX (week 7-10)  . Our litBecause of the frequently observed parallel occurrence of AHA and malignancies, our patient was worked-up in-depth regarding a possible malignant trigger for AHA and specific AHA treatment with immunosuppression including steroids, CYC and RTX was initiated . BecauseAs wide-ranging vaccination programmes are ongoing worldwide, post-marketing surveillance is essential for the safe delivery of the different SARS-CoV-2 vaccines. The detection and transparent communication of any adverse events including rare complications is important. This is especially relevant since these unusual but severe complications require specific diagnostic work-up and treatment. This case illustrates that a thorough diagnostic work-up for malignancy is mandatory at the diagnosis of AHA, even if other immune-mediated triggers seem equally likely. Moreover, oncological follow-up should be guaranteed, seeing as the severe immunosuppressive treatment that can be required leads to an increased risk of new or newly un-masked, rapidly proliferating malignancy. Our report aims to sensitize clinicians in the field to this rare but potentially severe complication to encourage prompt recognition and diagnosis of AHA, a thorough investigation of possible concurrent triggers, as well as timely treatment once found.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.MP and BT conceived the case report, collected and analyzed data and co-wrote the manuscript. MP, CS, and BT were directly involved in the treatment of the patient. CM performed histological evaluation. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Combined with the deconvolution algorithm, we demonstrated the good capabilities of scene reconstruction and depth imaging using a theoretical simulation and achieved a depth measurement error of only 3.42%.Depth imaging is very important for many emerging technologies, such as artificial intelligence, driverless vehicles and facial recognition. However, all these applications demand compact and low-power systems that are beyond the capabilities of most state-of-art depth cameras. Recently, metasurface-based depth imaging that exploits point spread function (PSF) engineering has been demonstrated to be miniaturized and single shot without requiring active illumination or multiple viewpoint exposures. A pair of spatially adjacent metalenses with an extended depth-of-field (EDOF) PSF and a depth-sensitive double-helix PSF (DH-PSF) were used, using the former metalens to reconstruct clear images of each depth and the latter to accurately estimate depth. However, due to these two metalenses being non-coaxial, parallax in capturing scenes is inevitable, which would limit the depth precision and field of view. In this work, a bifunctional reconfigurable metalens for 3D depth imaging was proposed by dynamically switching between EDOF-PSF and DH-PSF. Specifically, a polarization-independent metalens working at 1550 nm with a compact 1 mm The emergence of optical imaging has greatly enriched our lives and enhanced the human ability to perceive and reform the world. However, traditional cameras can only display two-dimensional plane projections of real 3D scenes without any depth information. With the rapid development of many emerging fields, deep imaging has attracted extensive attention in numerous vital applications, such as obstacle avoidance , productSome distinctive PSFs that are different from those of the traditional lenses can also help to obtain the depth information of objects like DH-PSF ,11. DH-PMetasurfaces ,21 that 2 aperture. Because of the nanosecond-level conversion speed of GST, our metalens can provide the 3D depth imaging capabilities with almost a single snapshot in completely coaxial imaging. Through the theoretical simulation, we have shown the clear reconstructed depth images of scenes with both a single object and multiple objects using our method, with only a 3.42% depth measurement error.In recent years, research on the active metasurface , whose oOur bifunctional metalens is a co-aperture device that features two different and complementary PSFs obtained in the A-state and C-state GST, respectively. This enables simultaneous scene reconstruction and depth acquisition. As shown in Φcode as ,36:(1)Φ=For the depth-invariant EDOF metalens, the wavefront coding term of the cubic phase term ,37,38 isng depth ,40  , which bmetalens , and theThe metalens includes nanorods ,47,48. Snanorods ,49. Figunanorods ,50.The simulation of depth imaging of a single-object scene with different depths was carried out first for our bifunctional metalens. The incident light with the information of a university emblem pattern was illuminated and passed through the metalens, and two blurry images were captured in the focal plane (receiving screen) by convoluting the incident scene with the EDOF-PSF and DH-PSF, as shown in In the case of the single-object scene, the accuracy of our bifunctional metalens has been demonstrated, where its scene and reconstruction process is relatively simple and the off-axis imaging aberrations had little impact on the depth precision as a little rotation offset because the object was located near the center of the field of view. Then, we implemented the simulation on the scenes of two objects with different depths located off-axis with larger angles. The actual depth of the university emblem is We have demonstrated a new method for 3D depth imaging using an active bifunctional metalens, which can enable depth estimation in an ultracompact and coaxial optical system without having to take multiple exposures compared to various 3D depth imaging techniques existed. By integrating the imaging lens and two wavefront coding functions into a single metalens device, the size is reduced significantly. This comes at the expense of introducing a larger off-axis aberration than a refractive lens system, resulting in the focal shift and rotation offset. Performing the functionality of EDOF-PSF and DH-PSF using a single-aperture metalens not only eliminated the parallax errors induced by space multiplexing, but also avoided the requirement of scene separation previously experienced in PSF engineering methods that utilized two juxtaposed metalenses, which can further improve the field of view and depth precision of the metalens. Through the theoretical simulation of 3D depth imaging on both single-object and double-object scenes, we have demonstrated the good scene reconstruction capabilities and depth precision of our bifunctional metalens. Compared to other metasurface-based depth cameras, our design can also accommodate a wider depth detection range, which is not limited to the scope of our work. By adjusting the aperture, focal length, and phase function factors  The scene images were convoluted with the PSFs generated by the metalenses to simulate the blurred cubic and helical images. (2) The reconstructed scenes were calculated by deconvoluting the cubic images generated by the EDOF metalens to restore the clear images using a regularization-filter based deconvolution algorithm. (3) After reconstructing the image, we segmented the image into several subregions of each object for depth estimation. We used the depth estimation algorithm based on the Wiener filter to deconvolute the helical image generated by DH-PSF metalens to obtain the estimated DH-PSF of each object. (4) The depth of the object was estimated by examining the rotation angle of the DH-PSF, comparing this against the theoretical angle-depth curve. For more information on scene reconstruction and depth estimation, please refer to


Alternative plant-based meats have grown in popularity with consumers recently and researchers are examining the potential health effects, or risks, from consuming these products. Because there have been no studies to date that have specifically assessed the health effects of plant-based meats on biomarkers of inflammation, the purpose of this work was to conduct a secondary analysis of the Study With Appetizing Plantfood – Meat Eating Alternatives Trial (SWAP-MEAT). SWAP-MEAT was a randomised crossover trial that involved generally healthy adults eating 2 or more servings of plant-based meats per day for 8 weeks (i.e. Plant phase) followed by 2 or more servings of animal meats per day for 8 weeks . Results of linear mixed-effects models indicated only 4 out of 92 biomarkers reached statistical significance. The results were contrary to our hypothesis, since we expected relative improvements in biomarkers of inflammation from the plant-based meats. Based on a growing interest among consumers, several companies have created and marketed plant-based meat products to accelerate the shift away from traditional animal meats. In the United States, the sales of plant-based meat products were over $900 million in 2019, and more than doubled in 2020. The increased demand for plant-based meats is due to greater consumer interest in health, as well as environmental and animal welfare. Additionally, some individuals that are interested in reducing their meat consumption find substituting plant-based meats to be a more manageable dietary modification compared with completely abstaining from meat products,6.Alternative plant-based proteins (or plant-based meats) are vegan or vegetarian products designed to resemble the taste and appearance of traditional burgers, sausages or other meatsv. animal meats (mostly red meats) on emerging and traditional cardiometabolic risk factors among 36 generally healthy adults.Based on a paucity of data assessing the potential health benefits or risks of plant-based meats, we recently conducted a clinical trial to specifically compare the effects of consuming plant-based meats . Recent trials have reported that red meat intake raises serum TMAO levels–11. Observational research has indicated that vegans and vegetarians have lower TMAO levels compared with meat eaters–13. In the SWAP-MEAT study, TMAO concentrations were significantly lower during the 8 weeks participants substituted the plant-based meats in place of the animal meats. Because TMAO is associated with inflammation, we were interested in examining whether substituting plant-based meats over animal meats has a differential effect on other biomarkers of inflammation. While there is some evidence that consuming plant-based diets can improve inflammation–17, there are no data specifically on the consumption of plant-based meats. Therefore, the purpose of the present study was to conduct a secondary analysis of the SWAP-MEAT study that assessed the effects of consuming plant-based meats v. animal meats on a broad range of biomarkers of inflammation. We hypothesised that some of the biomarkers would be improved while consuming the plant-based meats.The primary outcome of the Study With Appetizing Plantfoods – Meat Eating Alternatives Trial (SWAP-MEAT) study was serum concentrations of trimethylamine-N-oxide (TMAO), a molecule generated through gut metabolism that is associated with an increased risk for cardiovascular disease. The animal meats used in the present study were supplied from a San Francisco-based organic foods delivery service; the red meat sources were grass-fed. The plant-based meats used in the present study were supplied from Beyond Meat. Both types of meats were provided to the participants throughout the study. Other than the study products, participants were instructed to keep all dietary habits as consistent as possible between the two phases, such that the only dietary changes were the consumption of the plant-based meat products or the animal-based meat products. Participants consented to allow any frozen and archived blood samples that were available after completing the main study analyses to be used to examine additional factors that were been specified in the original protocol. Complete details of the original study have been reported elsewhere. Participant enrollment began on 5 December 2018 and continued through 9 July 2019. The date of final follow-up data collection was on 5 December 2019.The SWAP-MEAT  was a randomised crossover design that involved participants eating at least 2 or more daily servings of plant-based meats for 8 weeks (Plant-based phase) followed by 2 or more daily servings of animal meats for 8 weeks  (or vice versa). A single serving size was 3–4 ounces per product. Complete details of the nutritional profile of the plant-based meat and animal meat products can be found in the published manuscript of the original studyTo be eligible for this trial, participants were required to have a stable dietary history, defined as neither introducing nor eliminating a major food group in their diet for at least the previous month.v. Animal→Plant) was performed in block sizes of 4 by an independent statistician. Pairs  were randomised in block sizes of 2. Participants did not learn of their diet sequence until they completed all baseline measures and surveys. Laboratory technicians and study staff conducting blood and stool analyses were blinded to the diet sequence.Randomisation to one of the two diet sequences , having a body mass index (BMI) >40, LDL-C >190 mg/dl, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >90 mmHg, clinically significant or unstable pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality, or pregnancy. Individuals were excluded or had their study start date delayed if within the past 2 months they took systemic antibiotics, antifungals, antivirals or antiparasitics, corticosteroids, cytokines, methotrexate or immunosuppressive cytotoxic agents known to affect the microbiome.2 . Specific inflammatory biomarkers were selected for primary analysis based on a review of previous literature regarding biomarkers that were both available within the Olink panel and that had been reported to change in response to increased consumption of plant-based foods: interleukin-6 (IL-6), interleukin-18 (IL-18) and tumour necrosis factor (TNF)–17. We also selected three additional biomarkers that were reported to improve in previous nutrition studies in response to dietary change. The other three biomarkers were: interleukin-12 subunit beta (IL-12B), interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) for the main analysis based on these being some of the most commonly analysed biomarkers of inflammation from the literature on dietary patterns and inflammation .Data for inflammatory biomarkers were collected from participants’ blood samples at baseline, week 8, and week 16. The data were analysed from Olink Proteomics using the 92 inflammation-related protein biomarker panel (ammation (19). The–23. Linear mixed-effects models were conducted to compare changes in the biomarkers of inflammation from baseline and the end of each dietary phase (weeks 8 and 16) to determine if the changes were significantly different for the Plant-based phase compared to the Animal phase, adjusting for the fixed effect of diet order (i.e. study arm).Data were analysed in R version 3.6.3. Primary used for modelling were ‘lme4’ and ‘lmerTest’. The participants ate similar amounts of calories, macronutrients and servings of plant-based meat or animal meat products  throughout the intervention. Complete details of adherence are available elsewhereP = 0·01), Neurotrophin-3 (NT-3) , changed from baseline to the end of the Plant-based phase (Supplementary Table S3). FMS-like tyrosine kinase 3 ligand (FLT3L)  (Supplementary Table S4). Interleukin-22 receptor, alpha 1 (IL22RA1) increased in both phases  and .For the paired within-phase scores, only four biomarkers reached statistical significance. Interleukin-7 (IL7)  concentrations for any of the studies that assessed vegetarian diets for a duration of 6 months or less. Their sensitivity analysis indicated that the impact of vegetarian diets on CRP was more obvious for participants following the diet for at least 10 years. While CRP is not included in the Olink panel, some of the other biomarkers in our analysis (IL-6 and TNF) were also reported to improve in previous meta-analyses–17; therefore, it is possible that the length of time for substituting plant-based meats in place of red meats within this study was too short to achieve detectable improvements in systemic inflammation.This secondary analysis of the SWAP-MEAT randomised crossover trial assessed changes in biomarkers of inflammation when participants ate two or more daily servings of plant-based meats . In general, highly processed foods are associated with increased weight gain and an increased risk for a number of leading chronic health conditions. The plant-based meat products used in our study would fit the definition of ‘ultra-processed’ foods, due to a number of added ingredients used to enhanced the flavor and texture of the meats. Therefore, it is possible that the plant-based meats may not have any benefit to improving inflammatory biomarkers due to the products being highly processed. However, others have noted that plant-based meats ‘are often perceived as low-quality, ultra-processed foods. However, we argue that the mere industrial processing of ingredients of plant origin does not make a PBMA product ultra-processed by default.’ Additionally, recent work conducted by van Valiet et al. on the metabolomic profiling that compared a plant-based beef substitute to grass-fed beef demonstrates the complexity in trying to compare and understand nutritional adequacy of plant-based meat products to animal meats, since both foods assessed both contained and lacked differing nutrients with potential benefits to health.A second explanation for the modest changes in biomarkers of inflammation is that the mere substitution of plant-based meats over animal meats is not sufficient enough by itself to improve systematic inflammation. Only replacing animal meats (which comprised ~25 % of our participants’ energy intake in this study), but keeping all other dietary components the same, may not be enough to improve chronic inflammation, since the majority of participants’ foods were self-selected and likely did not change during the intervention. An overall healthy, plant-based diet may have yielded different results, since the focus of plant-based diets is to maximise the consumption of nutrient-dense foods like fruits, vegetables, nuts, wholegrains and seeds, while minimising the consumption of processed foods and animal foods. Also, reductions in animal meat consumption, particularly red and processed meats, have been widely reported to have beneficial impacts on environmental sustainability.Other potential benefits of substituting plant-based for animal meats have been reported. A recent randomised clinical trial noted positive changes in the gut microbiome among participants that substituted ~4–6 servings of plant-based meats per week in place of animal meats,30. This may impact the generalizability and interpretation of our results. Finally, the present study utilised only Beyond Meat products. There are numerous plant-based meat products with different ingredients or formulations, therefore the findings may not be generalisable to the consumption of other plant-based meat products.The strengths of the SWAP-MEAT study were minimal missing data from all participants, the crossover design of this trial allowed each participant to serve as their own control, and the strong dietary adherence to both dietary conditions. There were also some limitations to the study. Only the plant-based meat and animal meat products were controlled, while the remainder of the diet was self-selected, which limits the researchers’ control over the portion sizes or specific food selection. However, this does allow for increased external validity and generalizability. Our sample was ~66 % female and existing research on gender differences in inflammation and immune functioning suggest that women have higher levels of inflammation and poorer immune functioning. Future research may benefit from longer study duration periods.In conclusion, while the results of the main trial indicated several improvements in CVD risk factors, including TMAO, for the plant-based meats, no differences in the selected biomarkers of inflammation were observed