Purpose: Competency assessment standards for Critical Care Ultrasonography (CCUS) for Graduate Medical Education (GME) trainees in pulmonary/critical care medicine (PCCM) fellowship programs are lacking. We sought to answer the following research questions: How are PCCM fellows and teaching faculty assessed for CCUS competency? Which CCUS teaching methods are perceived as most effective by program directors (PDs) and fellows. Methods: Cross-sectional, nationwide, electronic survey of PCCM PDs and fellows in accredited GME training programs. Results: PDs and fellows both reported the highest rates of fellow competence to use CCUS for invasive procedural guidance, but lower rates for assessment of deep vein thrombosis and abdominal organs. 54% and 90% of PDs reported never assessing fellows or teaching faculty for CCUS competency, respectively. PDs and fellows perceived hands-on workshops and directly supervised CCUS exams as more effective learning methods than unsupervised CCUS archival with subsequent review and self-directed learning. Conclusions: There is substantial variation in CCUS competency assessment among PCCM fellows and teaching faculty nationwide. The majority of training programs do not formally assess fellows or teaching faculty for CCUS competence. Guidelines are needed to formulate standardized competency assessment tools for PCCM fellowship programs.  Goal-directed critical care ultrasound (CCUS) has become a necessary skill set for clinicians managing critically ill patients. The Accreditation Council for Graduate Medical Education (ACGME) includes CCUS among the core procedural requirements specifically for trainees in anesthesia and emergency medicine residencies Previous surveys of pulmonary and critical care medicine program directors demonstrated a heavy emphasis on informal bedside teaching of ultrasonography skills despite low reported levels of CCUS competency among faculty (i.e. PCCM attendings that routinely work and train fellows in the workplace setting) Better understanding of these gaps will allow for more transparency among pulmonary-critical care fellowship training programs regarding CCUS competency assessment of fellows and faculty, and allow for better standardization among programs nationwide. Our objectives were to investigate perceptions and methods utilized by fellows and teaching faculty in U.S. training programs to achieve and assess competency in CCUS.This study was approved by the New York University Grossman School of Medicine (NYUGSOM) Institutional Review Board (s18-00282). We conducted two cross-sectional surveys on CCUS competency from September to December of 2018: a survey of ACGME-accredited PCCM fellowship program directors or their designees, and a survey of PCCM fellows in ACGME-accredited programs. Surveys were designed through an iterative process of development that incorporated feedback from three groups at our institution: faculty experts in CCUS, PCCM fellowship program key clinical faculty, and senior PCCM fellows. The surveys were distributed via email to 148 PCCM fellowship program directors in the U.S. and Canada by the Association of Pulmonary and Critical Care Medicine Program Directors (APCCMPD). We asked PDs or their designee to complete the online PD survey, and forward a link to a second online survey to their fellows. We sent follow-up emails once a month for two months. The PD survey asked questions regarding methods used to teach CCUS to their fellows and their perceived effectiveness, perceived CCUS competency of their fellows and their teaching faculty that work with their fellows, and methods used to assess CCUS competency of their fellows and teaching faculty (see Appendix A for full PD survey). The Fellows survey asked questions regarding methods used to learn CCUS and their perceived effectiveness, their performance numbers of CCUS examinations, their perceived CCUS competency, and methods of CCUS competency assessment used by their programs (see Appendix B for full Fellows survey). Both surveys captured basic demographic information about respondents and training programs. Survey responses were anonymous and no personally identifiable information was collected. Survey study data was collected and managed using REDCap® (Research Electronic Data Capture) electronic data capture tools hosted at NYU Grossman School of Medicine Forty program directors completed the PD survey ; the total number of fellows that received survey invitations is unknown and a response rate cannot be definitively calculated but we estimated a response rate of 18%. Program and fellow demographics are described in Table 1. The vast majority were combined PCCM fellowship programs , academic , and moderately sized . Responding fellows represented a spectrum of training years .The majority of PDs thought the vast majority (76-100%) of their faculty were competent to perform US-guided vascular access (62%) and US-guided drainage catheter placement (64%). The majority of PDs (59%) felt that the majority or vast majority (51%-100%) were competent in lung/pleural US. However, only a minority of PDs believed that the majority or vast majority (51%-100%) of their faculty were competent in goal-directed cardiac echo (36% of PDs), abdominal/kidney US (23%), and lower extremity DVT studies (18%).We also performed a sub-analysis to explore if PD’s perception of faculty CCUS competence correlated with their perception of fellow CCUS competence and the strength of that correlation. Spearman’s rank correlation was computed to assess the relationship between PD’s perception of faculty competence and fellow competence for the 5 different CCUS examinations. There was a statistically significant positive correlation for goal-directed echo, r(38) = [0.436], p=0.006; and DVT studies, r(38) = [0.624], p <0.001. It was not statistically significant for US-guided vascular access (p=0.05), US-guided drainage catheter placement (p=0.271), or lung/pleural US (p=0.089).Methods of teaching and learning CCUS and their perceived effectiveness are documented in Table 2. Utilized methods of teaching CCUS (PD survey) and methods of learning CCUS (Fellow survey) were similar for the two surveys--local lecture-based teaching , directly supervised bedside CCUS exams with feedback , local hands-on workshops , and self-directed learning . Slightly lesser use included regional/national courses , case-based didactics , and unsupervised archival of images with subsequent review for teaching . PD and Fellow perceptions of usefulness for these different teaching/learning methods were similar. Percentage of PDs and Fellows that perceived the different teaching/learning methods as “very” or “extremely useful” on 5-point Likert scale were: hands-on local workshops , directly supervised bedside CCUS exams with feedback , regional/national courses , local lectures , local case-based conferences ; unsupervised CCUS with archival of images and subsequent review  and self-directed learning  were rated as less useful.Number of each CCUS examination performed by fellows over their fellowship is displayed in Figure 1. Percentage of fellows performing greater than 20 examinations varied by specific CCUS examination type: 90% for US-guided vascular access, 68% for US-guided drainage catheter placement, 69% for goal-directed echocardiography, 66% for lung/pleural US, 33% for abdominal US, and 19% for DVT studies.Program Director and Fellow Surveys: Methods of Assessing Fellow and Faculty CCUS Competency Methods of assessing fellows for CCUS competency are detailed in Table 3. The majority of PDs (54%) report never formally assessing fellows for CCUS competency, and the majority of fellows (67%) also reported never receiving formal competency assessment. Of the programs that do assess their fellows for CCUS competency, the most used method was global assessment by expert faculty . Half of PDs who engage in fellow CCUS assessments reported using formal review of archived real patient images, practical exam on real patients, and use of a standardized assessment tool. However, fellows report all methods other than global assessment by faculty to be used in the minority of their programs. Of the programs that do assess their fellows for CCUS competency, the specific CCUS exams being tested varied: procedural guidance 61% use on PD survey and 46% use on fellow survey; goal-directed Echo 78% and 62% respectively; lung/pleural US 67% and 59%; abdominal/kidney US 33% and 38%, and lower extremity DVT study 50% and 35% respectively.Ninety percent of PDs reported never assessing their teaching faculty for competence in performing CCUS examinations, and 8% did so only pre-employment. Given the very low prevalence of faculty competency assessment in general, data on methods of assessing faculty competence or specific examinations being assessed were deemed too small to draw conclusions and thus not reported.Regarding the documentation of CCUS competency, only 28% of PDs and 7% of fellows reported having a requirement for completion of a designated number of CCUS examinations prior to fellowship graduation, and only a small minority utilize an electronic portfolio to save their clips and images (18% per PDs and 6% per fellows).etails the percentage of fellows at a given fellowship program who attain competency to independently perform basic CCUS examinations by the end of fellowship training, as well as percentage of teaching pulmonary and/or critical care faculty at a given institution currently competent to perform these same CCUS exams. The percentage of PDs that believed the vast majority (76-100%) of their fellows attain competence varied by the specific CCUS examination type—very high perceived percentage of competence for vascular access and drainage catheter placement (97% of PDs for both), moderately perceived percentage of competence for lung/pleural US (71%), and lesser perceived percentage of competence for goal-directed echocardiography (47%), lower extremity DVT study (37%), and abdominal/kidney US (26%). Fellows’ perceptions generally agreed with PD competency perceptions for vascular access and drainage catheter placement, with fellows agreeing or strongly agreeing in their competence , as well as for lung/pleural exam (86% agreement with competence) and lesser perceived competence in DVT studies (50%) and abdominal/kidney US (44%). However, fellows perceived their competence higher for goal-directed echo (77% agree or strongly agree with competence) compared with PD perceptions. Breaking down fellow perceived competency by year of training, all years reported high perceived competency in US-guided vascular access  and US-guided drainage catheter placement . A stepwise pattern of increasing perceived competency was seen for goal-directed Echo  and lung/pleural US . However, rates of competence by year remained relatively flat/plateaued regardless of year of training for abdominal US  and DVT study . CCUS is a complex skill that combines cognitive knowledge along with psychomotor image acquisition skills and affective attitudes, and has become essential in daily practice for intensivists at the bedside Prior surveys of PCCM faculty and trainees have demonstrated heterogeneous institutional practices and methodologies to assess competency Interestingly, these levels of perceived competence were mirrored by fellow-reported experience with the different CCUS examinations, as most fellows reported greater experience with US-guided placement of vascular access devices or drainage catheters , goal-directed echocardiography and lung/pleura assessment but less abdominal and DVT ultrasound experience. About half of fellows reported performing fewer than 10 abdominal or DVT ultrasounds. ACCP/SRLF expert consensus guidelines do not specify the number of each US examination type recommended for CCUS competence A survey of 67 surgical critical care fellowship program directors reported the following exams as “very important”—FAST exam (75%), central venous access (80%), transthoracic echo (47%), DVT study (3%), and abdominal US for biliary pathology (1.5%) Regarding CCUS competency assessment, we found in this study 54% of PDs and 67% of fellows reported that their programs never conduct formal competency assessments for CCUS. Among the programs that reported conducting formal assessments, a global assessment by expert faculty was the most common method cited by both PDs and fellows. Among those programs that do formally assess their fellows, the majority do not test specifically for competency in DVT studies or abdominal ultrasound. Additionally, there is a lack of use of archival review with feedback as well as development of ultrasound portfolios. Prior studies have documented the issue of poor faculty competence in CCUS as a barrier to training Given the lack of formal assessment of CCUS competency of faculty, it is uncertain what information or data PDs used to answer our survey questions on faculty competence– institutional delineation of privileges, direct observation, gestalt, or other. Of note, we saw a correlation with PD perception of faculty CCUS competency with their perception of fellow CCUS competency for goal-directed echo (moderate correlation) and DVT studies (strong correlation). This is of uncertain significance, as it could reflect causality , or could represent PD’s inability to differentiate fellow from faculty competence due to lack of tangible metrics for the latter. Future studies to better understand the relationship between fellow and teaching faculty CCUS competency are warranted. PDs and fellows agreed on preferred methodologies for learning CCUS. Both groups reported that regional/national ultrasound courses, hands-on institutional workshops and directly supervised bedside CCUS exams were their most preferred approaches to learning CCUS, reinforcing concepts of learning through active processes. Regional CCUS courses including hands-on workshops with expert faculty have been found to be feasible and efficient in providing much needed hands-on training in CCUS Unsupervised CCUS exams, self-directed learning and lecture-based teaching were the least favored approaches to CCUS education. Brady et al. had determined through their 20-item survey of PCCM program directors that the most common method of learning CCUS was in fact unsupervised, independent bedside learning Our survey has several strengths and limitations. Unlike previous studies, our survey included perceptions of both program directors and fellows and found a general agreement on most topics. Our findings on the perceptions of program directors with respect to the competency of clinical teaching faculty to perform CCUS have not been described previously. The major limitation of our study was the small sample size compared to all PCCM training programs which could introduce selection bias and limit the overall generalizability to all current practices. However, the consistent data from both fellows and faculty does help with overall validity of the themes that emerged from the results, and the heterogeneous distribution of academic and affiliated hospitals improves the generalizability of the findings. However, given the small sample size of this study, we would caution that the results should be viewed as intriguing but ultimately hypothesis-generating and in need of future targeted studies to expand upon this work. Also, as this is a cross-sectional survey, there could be recall biases from the PD or fellow respondents. As stated above, it is uncertain what information PDs used particularly for faculty competence given the overall lack of faculty assessment. We also relied on PDs to forward a survey link to their fellows, introducing another element of potential sampling bias to fellow responses as there was a potential gatekeeper deciding to forward or not the survey to their fellows. Thus the assumption we made is that the responding PDs and fellows likely represent the same training programs, and thus the aggregate data is representative of the same training programs. This assumption is bolstered by the Demographic information detailed in Table 1 which shows very similar PD and Fellow survey demographics . However, as the data collected were anonymous, we expect the fellows to have been truthful and accurate in their responses. Lastly, given the anonymous nature of the data collection, we were able only to carry out analyses in aggregate, but unable to carry out detailed analyses of associations between PD and fellow responses from the same program.Our survey lays a foundation for future directions in the applicability and training of CCUS in clinical practice. Our exploratory analysis suggests that program director and fellow perspectives on CCUS competency overlap substantially; future surveys of PDs only might therefore be sufficient. It is also currently unknown how the COVID-19 pandemic may have impacted CCUS training despite high utilization of CCUS in intensive care units. This may help further improve our teaching practices and develop methodologies using advanced tools such as portable ultrasounds with remote access capabilities in the setting of contact precautions, virtual training and feedback sessions. It is currently unknown if CCUS training methodologies differ between CCM only programs vs PCCM programs and country-wide, survey-based studies are needed to include more CCM only programs.Our study highlights substantial heterogeneity in the CCUS teaching and competency assessment methods among ACGME-accredited PCCM programs in the United States. We found the perceptions of PDs and fellows were in general agreement with high levels of perceived competency to perform CCUS-guided procedures and lung/pleura assessment but deficiencies in the competent performance and interpretation of abdominal and lower extremity diagnostic venous ultrasonography. We also found that the majority and vast majority of programs do not assess their fellows and teaching faculty respectively for competence in CCUS, highlighting a major area of programmatic and curricular need. Our survey also demonstrates that active learning through regional and local hands-on workshops and directly supervised bedside CCUS exams were perceived as extremely useful, whereas, unsupervised CCUS exam, self-directed learning and lecture-based learning were perceived as less useful by both PDs and fellows. These findings suggest that further studies and guidelines are needed to formulate standardized competency assessment tools across all PCCM/CCM fellowship programs. MHA had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. MHA and DP contributed substantially to the study design, data analysis and interpretation. MHA, HD and DP contributed substantially to the writing of the manuscript. The authors have no relevant conflicts of interest to disclose.Appendix AAppendix A


Biological events occurring in the human brain are elegantly tuned to impart diverse emotions and elaborate behavioral patterns. The role of signaling pathways often changes during the progression of CNS disorders, and there is remarkable spatial heterogeneity in cell types and molecular expression profiles over the brain. Therefore, a full temporal and spatial illustration of the pathological progression of CNS disorders would benefit the development of novel therapeutic strategies. In this Research Topic, 6 articles, including high-quality original research articles and comprehensive reviews, discuss the spatiotemporal regulation patterns of CNS disorders and emerging techniques in this field.Zou et al. explored the cell type-specific modulatory roles of dopamine receptor D1 (D1R)- and D2R-expressing medium spiny neurons in the nucleus accumbens shell in TLE. They found that cell-type-specific inhibition of either D1R-MSN or D2R-MSN alleviated TLE seizures by reducing the number of secondarily generalized seizures and improving seizure stages, without altering the onset time of focal seizures. The data of the aforementioned study along with other studies suggest that different brain areas and cell populations participate in seizure initiation, propagation and termination, thereby highlighting the necessity of demonstrating the spatial heterogeneity of pathological mechanisms of epilepsy.Temporal lobe epilepsy (TLE) is the most prevalent focal seizure, which is highly likely to progress to generalized seizures. Here, Zhou and Zhang. discussed the cell type-specific role of oligodendrocytes in various CNS disorders and delineated the contribution of myelin to neuronal activity. Interestingly, neuronal excitability can also affect myelin functions. The authors overviewed the potential strategies for myelin regeneration through the precise modulation of neuronal activity.Similarly, Yi et al. reviewed the temporal regulation of key biological events that occur during neurodevelopment after experiencing febrile seizures. Febrile seizures are quite common during early childhood (-4%)   and receLai et al. examined the molecular mechanisms involved in the treatment of chronic pain using sinomenine, an active ingredient in the natural plant ‘sinomenium acutum (Thunb.) Rehd. Et Wils’, while focusing on its regulatory roles in distinct immune cell subpopulations. Sinomenine can regulate the interaction among different immune cells, immune cells and neurons and glial cells and neurons to confer immunosuppressive effects.The aforementioned studies dissect pathological mechanisms of CNS disorders from a spatiotemporal perspective. Similar research approaches can also be used to study the pharmacological mechanisms of drugs and other functional compounds. Wong et al. proposed a novel electrochemical localized oxygen scavenging system (eLOS) to induce hypoxia in vitro with spatiotemporal precision. Focal hypoxia is very common in multiple diseases such as ischemic stroke, cardiac arrest and dementia; however, the currently available experimental model of spatially restricted ischemia is limited. Using the eLOS platform, Wong et al. successfully induced axon-restricted hypoxic stress in human cortical neurons and found that localized axonal hypoxic stress induced neuronal death even when the somas remain in the normoxic culturing condition. These findings indicate the potential of the eLOS platform in studying cellular and subcellular changes in white matter after an injury and other hypoxic insults.Studies focusing on the spatiotemporal pathological mechanism of CNS disorders will benefit from the newly developed techniques providing spatiotemporal information. Ya et al. illustrated working principles and provided examples of the application of cutting-edge spatially resolved transcriptomic technologies in studying CNS disorders. The rapid development of these technologies will eventually provide a deeper understanding of the molecular mechanisms underlying CNS disorders.Furthermore, Overall, it has become inevitable to elucidate the pathological progression of CNS in high spatiotemporal resolution. We hope that this Research Topic will help readers understand CNS disorders from a highly spatiotemporally precise perspective.


We thank Drs. Sutt and Fraser for their insightful commentary on our publication. They open an important debate on tracheostomy timing and outcomes of interest.We concur that for decades, research has focused on “traditional” outcomes such as mortality and length of stay (LOS). Additionally, focus on tracheostomy-specific outcomes including swallowing, and communication may aid efforts to improve recovery after intensive care unit (ICU) discharge.Our analysis of > 17,000 critically ill patients with severe stroke attempted to clarify whether tracheostomy timing is an important piece of the stroke management puzzle .We found that early tracheostomy does not impact neurological outcome (mRS). This was reflected in the SETPOINT2 trial, where 75% of patients in each group experienced poor neurological outcome  despite active rehabilitation efforts (~ 70% of patients were discharged to rehabilitation facilities) [We recognise that, strictly speaking, the timing of tracheostomy should not substantially impact neurological outcome. Studies often inadequately separate early and late groups . The phEvidence on patient-centric outcomes in this population is limited. Our work humbly sought to quell decades of debate on the impact of tracheostomy timing on mortality, neurological outcome (mRS), and LOS, in patients with severe stroke. Given our findings, we commend future efforts to protocolise reporting of additional patient-centred outcomes such as speech , swallowing   and psyc


Editorial on the Research TopicUrothelial carcinoma of renal pelvis and ureter, prognosis and recent advancesUrothelial carcinoma of the renal pelvis and ureter is a prevalent malignancy primarily affecting the elderly population . Its incZhanghuang et al.). The study revealed that non-UTUC deaths accounted for the majority of mortality among patients with localized disease. This highlights the importance of considering non-cancer causes in the management of UTUC survivors. Moreover, UTUC was found to be the leading cause of death in patients with regional and distant stages, emphasizing the need for improved therapeutic strategies targeting advanced disease while considering the increased risk of death from non-cancer causes  survivors has provided valuable insights into mortality patterns. By utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, a large cohort of UTUC patients was examined  and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients. Using data from the SEER database, the study compared radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN). The results underscored the significance of accurate diagnosis and appropriate surgical intervention in RPUC patients. The study concluded that RN could lead to worse oncological outcomes compared to NU, emphasizing the importance of precise surgical planning and execution.Wu et al.).Another study emphasized the importance of distinguishing between radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN) in patients with renal pelvis urothelial carcinoma (RPUC). A retrospective analysis of data from the SEER database revealed that patients who underwent RN experienced worse overall survival (OS) compared to those who received NU. Furthermore, the study highlighted that the negative impact of RN on OS was more significant in patients with tumors larger than 4.2 cm . While no significant differences were observed in surgical outcomes between the two approaches, the study identified various predictive factors associated with adverse oncological outcomes. Age over 70, positive lymph node metastasis, upper ureter tumor location, and male sex were identified as potential risk factors. Additionally, higher surgical volume showed trends toward favorable outcomes in terms of overall survival and cancer-specific survival.A study utilizing data from the Taiwan nationwide upper urinary tract urothelial carcinoma (UTUC) collaboration database evaluated the outcomes of transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) . The findings indicate that patients who received chemotherapy (CT) combined with NU exhibited improved overall survival (OS) compared to those who received CT alone. This benefit was observed in both nonmetastatic and metastatic UTUC. The study emphasizes the potential advantages of NU in prolonging survival outcomes for patients with advanced-stage UTUC.A multicenter retrospective cohort study addressed the role of nephroureterectomy (NU) in stage IV upper tract urothelial carcinoma (UTUC)  was shown to have a negative impact on overall survival (OS), particularly in patients with larger tumors. Furthermore, while the choice between surgical approaches may not significantly influence outcomes, other factors such as patient age, lymph node metastasis, tumor location, and surgical volume should be considered for prognostic evaluation. Finally, the role of nephroureterectomy (NU) in stage IV UTUC demonstrates potential benefits in terms of overall survival (OS) for both nonmetastatic and metastatic cases. These findings underscore the importance of precise diagnosis and treatment among patients with UTUC.


Three years since the onset of COVID-19, pandemic-related trends in child sexual abuse (CSA) remain poorly understood. Common administrative surveillance metrics may have underestimated abuse during the pandemic, given youths’ limited access to mandatory reporters. Research using anonymous service-use data showed increased violence-related online help-seeking but overlooked youth-specific help-seeking for CSA during COVID-19. Understanding pandemic-related trends in CSA can inform abuse detection practices and mental health service provision for youth victims.The purpose of this study was to harness anonymous help-seeking data from the National Sexual Assault Online Hotline (NSAOH) to glean insights about CSA occurrence in the United States during the COVID-19 pandemic.We used an archival sample of victims who contacted NSAOH from 2016 to 2021 . We examined differences in the proportion of youth and adult victims contacting NSAOH during the first COVID-19 year (March 2020 to February 2021) compared to the prior year . Further, we compared key characteristics of hotline interactions among youth victims during the first COVID-19 year to the prior year (n=5913). Using joinpoint regression analysis, we examined linear trends in the number of monthly sampled youth and adult victims (excluding victims of unknown age) from 2016 to 2021 who discussed any victimization event  and who discussed recent events .Most youth victims were abused by family members prior to  and after  the onset of COVID-19. The number of youth victims contacting NSAOH spiked in March 2020 and peaked in November 2020 for all youth  and those discussing recent events . We observed a decline in youth victims into spring 2021 for all youth  and those discussing recent events . The number of adult victims discussing any victimization event increased steadily from January 2018 through May 2021  and then declined . Trends were stable for adults discussing recent events.This study extends the use of hotline data to understand the implications of the pandemic on CSA. We observed increased youth help-seeking through the NSAOH coinciding with the onset of COVID-19. Trends persisted when limiting analyses to recent victimization events, suggesting increased help-seeking reflected increased CSA during COVID-19. These findings underscore the utility of anonymous online services for youth currently experiencing abuse. Further, the findings support calls for increased youth mental health services and efforts to incorporate online chat into youth-targeted services. As we approach a postpandemic world, understanding trends in child maltreatment during COVID-19 remains vital for informing practices to detect abuse and ameliorate the effects of trauma. Evidence of pandemic-related trends in child maltreatment is conflicting, resulting in part from limitations of traditional surveillance strategies. Apparent declines in child maltreatment reflected in emergency room visits  may be aWhile youths’ perspectives are often assessed through self-report survey methodologies, indicators of online help-seeking are potentially valuable. Prior to the pandemic, youth actively sought help for experiences of abuse via online and text-based hotlines ,8, whichRecent work has explored trends in violence-related online help-seeking during the pandemic. Google searches related to child maltreatment increased during the pandemic ,12 but mA study of multinational child helplines  lacked cAmid these challenges, research on pandemic-related child maltreatment has largely overlooked child sexual abuse (CSA). However, concerns about victims’ physical and social isolation and accessibility to perpetrators during stay-at-home orders  are partWe advance knowledge by addressing limitations of previous work on 3 fronts. First, we examine online help-seeking for sexual violence among youth victims specifically. Second, we incorporate 5 years of observations (2016-2021), providing a broader picture of help-seeking patterns across the pre- and postpandemic onset time periods. Third, we delineate recent events to distinguish violence that occurred during the pandemic.The NSAOH is a US-based online hotline providing 24/7 anonymous crisis intervention services via desktop and mobile internet chat. RAINN , an anti–sexual violence organization in the United States, created and has operated NSAOH since 2006 to serve victims of sexual violence.Data collection via an in-depth online assessment  serves an integral role in hotline operations to identify areas for service improvement and staff training. Directly following the first chat session of their shift, staff record session information, such as event characteristics and topics discussed. Because information is not requested for the purpose of completing the assessment, data are often considered unknown . Staff receive instructions for assessment completion both within the assessment and through supplemental training.Data in this study represent a sample of all hotline chats in which the visitor discussed an experience of sexual or other interpersonal violence  between January 2016 and December 2021 . Additional information about hotline procedures, the organizational context, and sample inclusion criteria are available in Data used in this study were originally collected as part of ongoing internal program evaluation; thus, informed consent was not required. Analysis of this archival data for the purposes of generating generalizable knowledge of online hotline users and sexual violence experiences was deemed exempt by the Advarra institutional review board under category 4 of the Revised Common Rule.We examined differences in the proportion of youth  and adult (aged 18 years and older) victims during the first COVID-19 year (March 2020 through February 2021) compared to the year prior , with victims of unknown age excluded . Among youth (n=5913), we compared perpetrator type (family vs nonfamily), perpetrator living status (currently living with vs not currently living with the victim), event timeframe , and event frequency (repeated abuse vs single occurrence) during the first COVID-19 year compared to the year prior. These analyses used the chi-squared test with pairwise exclusion of missing data; analyses used SPSS .To contextualize trends in youth help-seeking, we used Joinpoint  to examine linear trends in the number of monthly sampled victims by age group from 2016 to 2021 among all youth and adult victims . Among youth, we noted statistically significant but small shifts in the proportion of chats that involved family-perpetrated assaults , perpetrators currently living with the victim , recent assaults , and repeated assaults . Inflection points reveal variability in the strength or direction (or both) of trends in the number of victims by age in our sample . Prior tThis study is the first, to our knowledge, to reveal increases in youth help-seeking for sexual violence coinciding with the onset of COVID-19. These increases peaked in November 2020 and were present for all youth victims and for youth victims discussing recent events. Although the number of adult victims increased, this trend was more gradual, preceded the onset of COVID-19, and was not present for those discussing recent events. Our finding that trends were sustained for recent events suggests an increase in youth affected by sexual violence during the pandemic rather than increased help-seeking among all victims for current and past events due to limited alternative support options.While our findings seemingly conflict with declines in abuse-related hospital visits and official reports ,2, evideMost youth who contacted the NSAOH—both prior to and during the pandemic—discussed repeated experiences of violence perpetrated by family members or someone else living with them. During the pandemic, we observed small proportional increases in youths’ chats that featured these characteristics, consistent with elevated violence driven by victims’ increased accessibility to perpetrators in the home amid limited contact with trusted adults . Future work should examine to what extent increased youth help-seeking reflected increased frequency and severity of ongoing violence predating the pandemic or cases of violence that began during the pandemic.The number of chats from youth began to decrease after November 2020. This decline could relate to youth having a greater ability to avoid perpetrators or opportunities to disclose to alternative sources of support as schools reopened in the summer and fall of 2020. However, because reopening policies were variable across the United States, driven by state and local government, this trend should be interpreted with caution.While reported trends were transitory, the effects of sexual abuse are not. Our findings reflect increased help-seeking by youth during the pandemic, an indication of rising demand for mental health services to treat trauma and its sequelae among youth. Given the national shortage of child mental health providers that predates COVID-19 , there iJoinpoint regression analysis allowed us to identify changes in the linear trend of victims’ hotline use from 2016 to 2021. While we interpreted the reason for some of these changes, their causes cannot be definitively ascertained from our analysis. We could not differentiate repeat hotline users from new users, which would help delineate new cases of abuse. Our data collection protocol prioritized the delivery of victim-centered services. We did not solicit information from visitors for assessment purposes, resulting in some missing data and limited demographic information. Future work could incorporate anonymous collection of demographics prior to service provision to enhance the utility of hotline data as a surveillance indicator of child maltreatment. Understanding the interplay of hotline supply and demand will also be useful because changes in staff availability  could affect the accessibility and use of services.Our study demonstrates the utility of anonymous online hotline data as a complementary surveillance indicator for child maltreatment that is transferrable to other public health priority areas . Increased help-seeking amid decreased safety at home also speaks to the utility of online support options for youth experiencing abuse. Preparing for future public health emergencies necessitates consideration of additional online communication options that allow youth to privately disclose abuse to trusted adults. Future work should explore how to safely incorporate these communication options into existing services, such as online schooling or telemedicine platforms.


Remyelination biology and the therapeutic potential of restoring myelin sheaths to prevent neurodegeneration and disability in multiple sclerosis (MS) has made considerable gains over the past decade with many regeneration strategies undergoing tested in MS clinical trials. Animal models used to investigate oligodendroglial responses and regeneration of myelin vary considerably in the mechanism of demyelination, involvement of inflammatory cells, neurodegeneration and capacity for remyelination. The investigation of remyelination in the context of aging and an inflammatory environment are of considerable interest for the potential translation to progressive multiple sclerosis. Here we review how remyelination is assessed in mouse models of demyelination, differences and advantages of these models, therapeutic strategies that have emerged and current pro-remyelination clinical trials. Multiple sclerosis (MS) is a chronic demyelinating, inflammatory and neurodegenerative disease of the central nervous system (CNS). Remyelination is a regenerative process by which oligodendrocytes restore myelin sheaths to demyelinated axons. Evidence from animal models indicate that remyelination can restore neuronal conduction , 1981, pRemyelination is robust in many animal models that have been used to study remyelination, which is somewhat discordant with the heterogeneous patterns of oligodendrocyte loss, demyelination and remyelination in human pathology-based studies of MS tissue . The mecThe inflammatory environment can modulate oligodendroglial properties including oligodendroglial survival, migration, differentiation, axon engagement and remyelination . AdvanceIn animal models, aging influences oligodendroglial properties  and prog14C has been used to investigate the age of oligodendroglia within MS lesions and this study indicated limited production of new oligodendrocytes within shadow plaques that may have undergone remyelination suggesting that mature surviving oligodendrocytes contribute to subsequent remyelination in human MS lesions (14C) prior to differentiation despite rodent studies indicating that OPCs can directly differentiate into mature oligodendrocytes without cell division  is an endogenous lysophospholipid that can be used to generate a focal demyelinating lesion by injection into white matter tracts and demyelination results through disruption of oligodendroglial cell membranes  leading In the lysolecithin model, myelin  and extrEthidium bromide, a DNA-intercalating agent, injected into white matter tracts creates a focal demyelinating lesion with a larger area of demyelination compared to lysolecithin . EthidiuCombining X-irradiation with ethidium bromide injection has allowed for the investigation of transplanted progenitor cells in a lesion environment devoid of endogenous remyelination potential . NeonataAged animals exhibit slower remyelination after lysolecithin and ethidium bromide injection  and agedCuprizone, bis-cyclohexanone-oxaldihydrazone, was first used as an animal model of demyelination in the 1960s . CuprizoMyelin loss occurs after several weeks of cuprizone ingestion and peaks at 4–5 weeks . One of Manipulation of astrocyte and microglial responses after cuprizone-mediated demyelination can influence remyelination. Ablation of astrocytes after chronic cuprizone treatment results in improved oligodendrocyte density, remyelination and motor functional outcomes . AstrocyThe role of T cells in cuprizone-mediated demyelination is unclear. T cells are present in cuprizone ingestion  and CD8 Toxin models have greatly facilitated the investigation of pathways involved in oligodendroglial proliferation, recruitment, differentiation and remyelination. Promising mechanisms that are under investigation in clinical trials for remyelination in MS that have emerged from investigation of remyelination in focal and systemic toxin models include LINGO-1 antagonism , Nogo-A The major advantages of toxin models are the robust remyelination response with stereotyped kinetics, separation of the demyelinating process from the regenerative process, minimal axonal degeneration, and decline of remyelination with aging that have allowed for discovery of targets that accelerate repair in an aged environment. While focal toxin models have these advantages, the short demyelinating insult and robust remyelination response are limitations. Diffuse CNS demyelination and white matter injury induced by cuprizone ingestion offers the advantage of an environment with prolonged oligodendroglial loss, neuronal stress and subsequent neurodegeneration, which may allow for the investigation of pathways that prevent neuronal degeneration and allow for the ability to assess motor  and physExperimental autoimmune encephalomyelitis (EAE) models are one of the most commonly used models to investigate the immunopathogenesis of MS . Immuniz35–55 peptide    and tranpt-mGFP) ,D. Signipt-mGFP) . Despitept-mGFP) , pharmacpt-mGFP)  and K-oppt-mGFP)  were abluprizone . Immunizl course . Remyelil course . The relon phase  and whet35-55 EAE does not resemble the clinical course of relapsing remitting or progressive MS. The high degree of neurodegeneration and minimal remyelination after the acute EAE phase represent challenges for the utilization of these models in assessing remyelination strategies.Active immunization models have many features that differ from human MS pathobiology and clinical course. The robust inflammatory response and resulting secondary demyelination, early neurodegeneration , sparingEncephalitogenic T cells from CNS antigen immunized mice or myelin-specific T cells isolated from T cell receptor transgenic lines can be used to induce neuroinflammatory disease upon adoptive transfer into naive hosts . A majorAdoptive transfer of myelin-reactive Th17 cells after acute cuprizone ingestion has been used as a model to investigate oligodendroglial responses in the setting of T cell mediated inflammation  and has Gfap-tTA) with tetracycline response element (TRE) upstream of IFN-γ sequence (TRE-IFN-γ) in a double transgenic line allows for temporal regulation of CNS IFN-γ expression upon removal of doxycycline  have been used to investigate demyelination and remyelination. Initial studies of transgenic mice with targeted expression of IFN-γ from the myelin basic protein (MBP) promotor  and gliaycycline . CNS IFNlination . Prolonglination  suggestiPlp-CreER™) with a diphtheria toxin subunit A (DTA) floxed stop reporter line (ROSA26-eGFP-DTA) results in oligodendrocyte apoptosis upon exposure to tamoxifen  results in oligodendrocyte death, widespread demyelination, microglia and macrophage reactivity, axonal damage and incomplete remyelination (Loss of function of transcription factor myelin gene regulatory factor (MYRF) that induces expression of mature myelin genes  in maturlination . Subsequlination . While tChronic encephalomyelitis viral mouse models share pathogenic features similar to MS  and may Theiler’s murine encephalomyelitis virus (TMEV) is a single-stranded RNA picornavirus that causes flaccid myelitis in mice  and can Mouse hepatitis virus (MHV) is a positive-strand RNA virus with neurotropic strains that can be used to induce a chronic demyelinating disease through intracranial or intranasal inoculation of susceptible mouse strains. An acute encephalomyelitis phase is followed by a secondary phase of demyelination and remyelination . MHV-spein vitro have been used to identify pathways with remyelination potential (High-throughput screens that evaluate the ability of compounds to promote oligodendrocyte differentiation otential . Many paotential .Assessment of remyelination in MS clinical trials has been challenging, with few validated clinical tools to assess remyelination in humans . MeasureAnimal models of MS with demonstrated remyelination capacity vary considerable in their mechanisms of demyelination, inflammatory infiltrates, degree of ongoing inflammatory activity, axonal loss and neurodegeneration and extent of remyelination. Focal toxin models offer the advantage of stereotyped remyelination after a short single demyelinating insult which has allowed for the investigation of factors that promote or inhibit this robust reparative response. A prolonged demyelinating insult predominated by corpus callosum and cortical demyelination and subsequent neurodegeneration and motor decline can be modelled with chronic cuprizone exposure and may share some features of the neurodegenerative process in progressive MS. Both cuprizone and EAE models induce inflammatory subsets of glia that are found in MS tissue and further investigation of how these subsets of glia contribute to ongoing inflammatory activity and promote or inhibit repair may offer insight into potential mechanisms to modulate remyelination in inflammatory settings. While no single animal model recapitulates the pathobiology of MS, considerations of the limitations and advantages of each model should be taken into account when investigating remyelination and translating animal model findings to human MS.DP and EH contributed to writing the manuscript. EF contributed to researching and generating the clinical trial table. 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.


Carotid web (CaW) and carotid free-floating thrombus (CFFT) are rare yet critical causes of ischemic stroke in young adults.A 54-year-old woman presented with a fluctuating right sensory-motor faciobrachial syndrome. A brain MRI scan revealed multiple small recent asynchronous cortico-subcortical ischemic foci in the vascular territory of the left internal carotid artery. A CT angiography identified a CFFT in the left internal carotid artery arising from an underlying CaW. The patient was treated with excellent clinical outcomes with carotid artery stenting and dual antiplatelet therapy.We provide a structured pathophysiological rationale connecting CaW and CFFT and highlight pivotal therapeutic implications. Further studies are needed to investigate this relationship and guide assessment and treatment. Etiological diagnosis of stroke in young adults is a challenging and critical aspect of neurovascular care. Indeed, patients affected by such devastating occurrences have an inherently longer time after the index event and can thus benefit most from adequate secondary prevention strategies . UnfortuCarotid web (CaW) and carotid free-floating thrombus (CFFT) are well-known yet often neglected causes of ischemic stroke in young adults. CaW defines a localized carotid intimal fibromuscular dysplasia presenting as a shelflike projection into the lumen of the proximal internal carotid artery , 4. ConvHereby, we describe a case of ischemic stroke due to a CFFT originating from a contiguous CaW. We illustrate the diagnostic and therapeutic implications of these two rare conditions, as well as their possible pathophysiological relationship.A 54-year-old woman presented to the emergency department with a two-day history of fluctuating right sensory-motor faciobrachial syndrome. The patient was an active smoker without further major cardiovascular risk factors. Specifically, she had a normal body mass index and no medical history of hypertension, dyslipidemia, diabetes, neurological or cardiovascular events. Additionally, she was not using estrogen-containing oral contraceptives and her family history was unremarkable for cerebrovascular events. Neurological examination on admission revealed a right inferior facial palsy NIHSS = 2). Brain CT scan and blood tests were normal. A minor stroke was suspected, therefore, the patient initiated dual antiplatelet therapy (DAPT) and was admitted to our Stroke Unit. A brain MRI scan revealed multiple small recent asynchronous cortico-subcortical ischemic foci in the left middle cerebral artery and a subacute/chronic ischemic lesion in the left head of the caudate nucleus, a territory of the recurrent artery of Heubner Fig. . Continu. Brain CWe report the case of an otherwise healthy young woman who presented with multi-embolic strokes caused by a CFFT stemming from an underlying CaW. The co-occurrence of these two conditions has been reported anecdotally, and the presence of thrombus superimposition on CaW was suggested to be a contributing factor to stroke recurrence –10. HoweRadiological differentials for CaW encompass atherosclerotic plaque with plaque rupture, carotid artery dissection, and fibromuscular dysplasia (FMD). However, the regular morphology of the filling defect, lack of calcium deposits and signs of intramural hemorrhage make atherosclerotic plaque unlikely in our patient. Furthermore, neither CTA nor DSA revealed the presence of an intimal flap, and no other stenotic segments were identified in our imaging studies, reducing the probability of carotid artery dissection and FMD.CTA has shown superior diagnostic accuracy compared to carotid US in diagnosing CaW . It is tAs a secondary prevention, our patient was successfully treated with CAS and transitory DAPT. Evidence of the best management is currently lacking in the literature. Indeed, secondary prevention strategies for CaW and CFFT are based on small case series and expert consensus, as no specific guidelines or clinical trials have been designed to date. Concerning CaW prevention, current strategies aim to avoid long-term complications arising from the high stroke recurrence rates. Although chronic pharmacologic management with anti-platelet agents would fall within current guidelines  also antWe described a case of CFFT and CaW co-occurrence focusing on their possible pathophysiological connection as well as diagnostic and therapeutic implications. Meticulous evaluation of non-invasive or invasive vascular imaging tests aiming to detect an underlying CaW in unexplained CFTT should be required. Carotid artery stenting and, eventually, thrombectomy might be a safe and effective secondary prevention strategy to kill two birds with one stone unless underlying thrombophilic conditions requiring anticoagulation therapy are present. Future studies are needed to estimate the frequency and understand the underpinning biologics of the co-occurrence of these two conditions in order to inform assessment and treatment.


Since organizational psychology is a broad and evolving discipline, the topic editors are pleased to announce sixteen articles that highlight new insights into how leadership, collective intelligence, intellectual capital, innovation, job performance, satisfaction advance the tradition, nature, and research methods of organizational psychology. The articles showcase a global perspective of new insights in organizational psychology from Asia, Europe, Middle East, Africa, North America, and Oceania. The authors explored new insights in organizational psychology through conceptual analysis, qualitative and empirical research, a brief research report, and a systematic review.There is a continual focus to expand and provide new insights on leadership theory and research (Lord et al., van Niekerk highlights the importance of psychosocial factors and elevated stress levels that limit a flourishing multi-cultural environment, stakeholder engagement and leader-follower relationships. The author recommends that organizations should promote a multi-cultural team to counteract elevated stress and to better manage psychosocial factors in an organization. Zhao et al. extend the literature on authoritarian leadership by providing a new perspective for authoritarian leadership practice. In comparison to previous research studies, the authors findings indicate authoritarian leadership generates positive employee wellbeing and creativity. Haar and de Jong explored the dark side of leadership personality to provide new insights on how the dark side of leadership could benefit an organization's performance rather than decreasing organizational performance. Latent transition analysis is introduced by Zyberaj et al. for helping organizational psychology researchers to analyze longitudinal data through an applied example utilizing psychological capital and leader-member exchange. The author findings indicates psychological capital is more likely to occur when leader-member exchange is high rather than low. Therefore, high leader-member exchange works hand-in-hand with high psychological capital.Janssens et al. extends the collective intelligence literature and research through a conceptual analysis on the dynamic granular tensions between the needs of the environment with the collective team behaviors over time. The authors explored various methods to help organizational psychology researchers unpack micro-level team behavior. Senawi and Osmadi research study findings reveal that relational capital plays a significant role with intellectual capital for improving property tax reassessment activities. Overall, the attitudes of local government officials must align with relational capital and intellectual capital for successful property tax reassessment performance.Fan et al. research study findings extend self-determination theory to reveal employees' perceptions on organizational support has positive and profound effects on employees' proactive innovative behavior through the satisfaction of basic psychological needs such as autonomy, competence, and relatedness. Liu and Zhang focuses on employees' paradox mindset on innovative performance through role breadth self-efficacy. Employees with a paradox mindset intentionally make innovative things happen through their own actions. Moreover, role breadth self-efficacy and individual ambidexterity play an important role in understanding how employees manage a paradox mindset and innovative performance. Song et al. provide new insights on how employees should manage innovation performance under time pressure. The authors research study findings indicate time pressure significantly improves innovation performance. Therefore, employees operating under time pressures should receive significant leadership support for improving innovative performance.From a new Chinese perspective, Xu et al. investigated the interdependence of psychological capital, social capital and human capital, including the three capital's impact on job performance. The authors study findings discovered new insights on configuration and casual asymmetry from psychological capital, social capital and human capital that affect job performance. Consequently, Xu et al. challenged previous studies' symmetrical regression relationship findings and extended the relationship among psychological capital, social capital and human capital within intelligent career theory. Moreover, high psychological capital plays a key role in high job performance. Sanclemente et al. explored inconsistencies from previous research studies that predict workers' health levels in linear models. The authors research study focused on differences among service sub sectors through linear and non-linear relationships within task complexity, job autonomy, user contacts, time pressure, and psychological and physical symptoms of employees. Overall, Sanclemente et al. research study findings on non-linear relationships indicate medium levels of task complexity from job demands should not exceed greatly to mitigate increased negative impacts to foster service sector employees' physical and psychological well-being in job satisfaction and performance.Levitats et al. provides new insights on unexplored contexts of emotional intelligence in the literature. Specifically, the authors explore the role played by emotionally intelligence in an organization's culture combined with supervisors' emotionally intelligent behaviors. The two-study research findings reveal process links between emotionally intelligent values and practices, and job demands between supervisor emotional intelligence behaviors that affect employee exhaustion and engagement. Chen Y. et al. systematic review provides deeper understanding on the relationship between pay for performance and job performance by highlighting the research studies that examine pay for performance and job performance in real work settings. The results of the systematic review complements the positive effects of pay for performance and job performance in work settings through contextual performance and task performance. In addition, the authors introduce two mediating variables namely, intrinsic motivation and pressure that integrates the positive and negative effects of pay for performance and job performance into one framework.López-Cabrera et al. research study is to explore potential factors that promote job satisfaction between volunteers and regular paid staff in non-profit organizations. The research study contributes to new understandings of the mechanism that promotes greater satisfaction from volunteer workers vs. regular paid staff through role ambiguity, role conflict and job performance. Chen C. et al. research study provides new insights on positive outcomes of customer incivility that could trigger employees' customer service behavior to challenge and extend the literature stream's focus on negative outcomes and customer incivility. The authors provide a more comprehensive understanding how customer incivility influences employees' behavior and the implications for revenge behavior and customer service behavior and performance in the work environment. Uzum et al. combine crab barrel syndrome and social comparison theory as a new approach for identifying precursors of crab barrel syndrome. The authors' research study findings indicate through social comparison theory that type A personality precedes crab barrel syndrome, especially when the work environment is highly competitive. Consequently, job performance for type A personalities requires strengthening the employee's self-esteem with group support to decrease crab barrel syndrome.The aim of In conclusion, the articles in this Research Topic provide examples of new insights that we find relevant and thought provoking for progressing further research into organizational psychology scholarship from multiple perspectives.MT: Writing—original draft. DT: Writing—review and editing. GG: Writing—review and editing.


Impairments in decision-making processes are believed to play an important role in both substance use disorders and behavioral addictions. Clinical and pre-clinical experimental testing provide complimentary insights on the psychobiological mechanisms of decision-making. The IOWA Gambling Task (IGT) assesses decision-making under ambiguity and risk, in which individuals are faced with four card choices associated with varying monetary reinforcer/loss contingencies. The rat Gambling Task is a pre-clinical version using palatable reinforcers as wins and timeouts mimicking losses. However, studies with interspecies comparisons in these tasks are lacking, but important to facilitate translation of information that may help unravel the complex processes of decision-making and generate clinical advances.This study explores decision-making strategies among humans and rats performing the IGT and rGT.A total of 270 young human adults performed a computerized version of the IGT, and 72 adult outbread male Lister Hooded rats performed the rGT. Performance was assessed and explored by normative scoring approaches and subgroup formations based on individual choices.Results showed that most humans and rats learned to favor the advantageous choices, but the overall level of performance differed considerably. Humans displayed both exploration and learning as the task progressed, while rats showed relatively consistent pronounced preferences for the advantageous choices throughout the task. Nevertheless, variability in individual choice preferences during end performance were evident in both species.Results are discussed in relation to procedural differences impacting performance and potential to study different aspects of decision-making. This is a first attempt to provide formal evaluation of similarities and differences regarding decision-making processes in the IGT and rGT from an explorative perspective.None Declared


Brain 2022).Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder affecting 1-2% of the population worldwide. Recent large-scale whole-exome sequencing (WES) studies identified hundreds of rare, highly penetrant genetic variations associated with ASD. Many of these genetic variations underlie particular genetic syndromes characterized by a variety of congenital anomalies in addition to the core ASD symptoms. Recently, we reported about certain ultrasonography fetal anomalies (UFAs) associated with later development of ASD  who have both fetal ultrasound and WES data. We used an integrative in-house bioinformatics pipeline specifically designated to identify gene-disrupting variants (GDVs) in a panel of >1200 genes associated with ASD according to SFARI gene database. Then, we compared the prevalence of GDVs in these genes between children with and without UFAs. Finally, we applied the Gene Analytics tool to disrupted genes in children with specific fetal anomalies to identify biological pathways associated with both ASD and these fetal anomalies.children with UFAs were more likely to carry GDVs in ASD genes than their counterparts even after adjustment to the sex differences between the groups , and this association was the most prominent with GDVs in the most notable ASD genes . Also, the study shows higher prevalence of children with GDVs in most anatomical systems, with UFAs in fetal size  and the head&brain  being the most prominent . In addition, children with UFAs had significantly more co-occurring mutations, and the number of mutations in a single fetus was significantly correlated with the number of UFAs .Overall, 115 ASD children were included in this study, of which 49 (42.6%) of them had UFAs in their ultrasound scans . Children with and without UFAs did not differ in their sociodemographic and clinical characteristics except for a significantly lower proportion of males in the UFA group . Notably, Image:Image 2:Our findings suggest distinct genetic mechanisms for ASD subtypes that are characterized by unique UFAs. These findings may form a basis for future prenatal screening approaches for ASD using both ultrasound and genetic testing. Our findings suggest distinct genetic mechanisms for ASD subtypes that arecharacterized by unique UFAs. These findings may form a basis for future prenatal screening approaches for ASD using both ultrasound and genetic testing.None Declared


Proteome stability  is critical for proper cellular functionality and consequently organismal health and it is ensured by an extensive compartment-specific network of machineries known as the proteostasis network (PN) . Key comDeclined proteasome functionality is a hallmark of aging and a major risk factor for the development of many age-related diseases such as neurodegenerative disorders and cardiomyopathies . On the Drosophila experimental in vivo model we previously reported that flies exposed to therapeutic PIs  display similar adverse effects with multiple myeloma patients treated with PIs, including both neurotoxicity and cardiac dysfunction [By exploiting the function . Recentlfunction ; these mfunction . Interesfunction ). In supfunction .Taken together, our findings provide mechanistic explanations for the heart-related adverse effects of therapeutic PIs, suggesting that proteasome dysfunction in the heart results in cardiotoxicity and systemic complications due to proteome instability, mitochondria disruption, redox imbalance and metabolic deregulation. Moreover, our therapeutically relevant finding that co-administration of autophagy inducers  exert beneficial effects on heart functionality, provide preclinical insights for alleviating PIs-induced cardiac adverse effects and thus preventing anti-tumor therapy discontinuation.


The ATTRv patient underwent heart transplantation because of progressive heart failure. Within the next two years, progressive myopathic symptoms and extracardiac tracer uptake on 99mTc-DPD planar scintigraphy were documented, attributable to ATTR amyloid myopathy. Interstitial amyloid deposits were confirmed by muscle biopsy in both patients, with a particularly high amyloid burden in the adipose tissue. This case report highlights the frequent concomitant presence of cardiac ATTR amyloidosis and ATTR amyloid myopathy. ATTR amyloid myopathy may precede cardiac manifestation in ATTRwt or occur after heart transplantation in ATTRv. Due to the high diagnostic accuracy of 99mTc-DPD scintigraphy for detecting ATTR amyloid myopathy and the emergence of novel therapeutics, it is important to increase the awareness of its presence.We identified two patients with transthyretin (ATTR) amyloid myopathy . Myopathy was the initial manifestation in ATTRwt, whereas it followed neuropathy and cardiomyopathy in ATTRv. The ATTRwt patient showed muscular tracer uptake on  This was particularly pronounced in ATTRwt and ATTR-Val122Ile and could be confirmed histologically as ATTR amyloid myopathy in a small subset of patients with Perugini grade 3 on 99mTc-DPD scans.7ATTR amyloid myopathy, which is characterized by intramuscular interstitial amyloid deposits leading to weakness in the upper and/or lower extremities may contribute significantly to morbidity.We herein describe two cases of ATTR amyloidosis (ATTRv and ATTRwt) with clinical, imaging, and histological evidence of ATTR amyloid myopathy, which is probably often underappreciated and underrecognized in routine clinical practice Table .Table 1C99mTc-DPD whole-body planar imaging . There was no family history of amyloidosis. The patient’s medical records were remarkable for bilateral carpal tunnel syndrome ten years and decompression for lumbar vertebral stenosis two years before diagnosis of ATTRv amyloidosis. Neurological examination at the time of diagnosis of ATTRv amyloidosis in 2015 revealed fatigue, paresthesia of the feet, and loss of Achilles tendon reflexes. Dyspnea, bilateral lower leg edema, muscle cramps, mild proximal muscle weakness, upper extremity paresthesia, and numbness in the upper and lower extremities developed over the following 1.5 years. In addition to heart failure treatment, the ATTR tetramer stabilizer tafamidis was started in 2017 when this substance was first available in Austria. Three years after the initial diagnosis, the patient underwent heart transplantation due to progressive heart failure. Tafamidis, which was paused perioperatively, was restarted seven weeks thereafter. On routine follow-up 12 and 19 months after successful heart transplantation, no evidence for recurrent cardiac amyloidosis was found on endomyocardial biopsy and 99mTc-DPD planar scintigraphy  showed minor abnormalities with a mixed pattern of mild neurogenic and myogenic changes.Serum creatine kinase (CK) levels were within the normal range.Figure Reticular deposits of homogeneous eosinophilic material, representing amyloid, were mainly observed in the perimysial adipose tissue. Interstitial deposition of amyloid was also found in endomysium of skeletal muscle. Interestingly, the ATTR amyloid load was greater in the surrounding adipose tissue than in skeletal muscle. Immunohistochemistry showed amyloid deposits immunoreactive for transthyretin Figure E-G.99mTc-DPD scintigraphy and cardiac magnetic resonance imaging. No pathogenic mutation could be detected and treatment with tafamidis was initiated in 2019. 99mTc-DPD whole-body planar imaging  after diagnosis of ATTRwt amyloidosis showing significant ATTR amyloid deposition  initially presented with bilateral lower leg edema, vertigo, numbness in the pretibial area, lower extremity muscle weakness and muscle cramps. The latter had already started 1-2 years before and was initially considered as side effect of statin use. In the absence of monoclonal proteins, diagnosis of cardiac ATTR amyloidosis was obtained by A low-grade sensorimotor axonal polyneuropathy of lower extremities was revealed in 2019. Myopathic changes in the left gluteal muscle could be detected one year later by EMG.CK levels were within the normal range.Figure Hematoxylin and eosin staining showed slight variation of fiber size and increase of endomysial connective tissue. Necrotic fibers were not seen, although few regenerating fibers were present. Single atrophic fibers were vacuolated and contained amorphous sarcoplasmic deposits suspicious of amyloid. These amorphous deposits were clearly identified as green birefringent amyloid deposits on Congo red staining and were immunoreactive for transthyretin Figure A-D.TTR gene have been described to date, characterized by a wide phenotypic heterogeneity.2 The ATTR-Val40Ile variant, which was diagnosed in patient 8 A similar course was seen in patient 99mTc-DPD planar scintigraphy 19 months after heart transplantation revealed pronounced muscular tracer uptake in the shoulder and gluteal regions in the absence of cardiac tracer uptake in the transplanted heart. At the same time the patient complained of progressive muscle weakness and muscle cramps. Biopsy from the deltoid muscle confirmed significant ATTR amyloid deposition. As there was no evidence of progression of the previously diagnosed neuropathy in the follow-up examinations, it seems likely that the patient's complaints were due to increased amyloid deposits in the peripheral muscles after heart transplantation.In ATTRv more than 140 mutations in the 9One possible explanation for the development and clinical presentation of amyloid myopathy could be that ATTRv amyloid binds to pre-existing ATTRv amyloid deposits with high affinity. Therefore, after heart transplantation and release of ATTR amyloid cardiomyopathy, ATTRv amyloid may preferably deposit on pre-existing, formerly subclinical, ATTRv amyloid deposits in skeletal muscle, causing posttransplant amyloid myopathy in our patient. Similarly, it was reported that amyloid cardiomyopathy may develop after liver transplantation in ATTRv patients, due to binding of wild-type transthyretins, produced by the transplanted liver, on pre-existing ATTRv amyloid deposits in the myocardium.7 In this study bone uptake on 99mTc-DPD scintigraphy increased over the 3 h imaging period, whereas cardiac uptake and soft-tissue uptake (mainly muscle) decreased over time. This seems to be contradictory to the Perugini grading system, which is based on the reciprocal and relative decrease in bone uptake on planar imaging. The authors postulated that bone uptake particularly in patients with Perugini grade 3 on 99mTc-DPD scans may be obscured by tracer uptake in overlying skeletal muscles. Extensive soft-tissue uptake may even obscure visualization of cardiac tracer uptake on planar imaging.7 Conversely, it is conceivable that extensive cardiac tracer uptake may obscure visualization of muscular tracer uptake. It must therefore be considered that in our patient amyloid myopathy was already present before heart transplantation but was not noticed due to this phenomenon. However, increasing muscular complaints suggest an increase in amyloid load after heart transplantation.Hutt et al reported that most patients with cardiac ATTR amyloidosis, especially ATTRwt and ATTR-Val122Ile variant showed muscular tracer uptake on bone scintigraphy.Despite clinical improvement of muscular complaints under gene silencing therapy, a scintigraphic follow-up examination in November 2021 (40 months after heart transplantation) still showed a marked increase in muscular tracer uptake in shoulder and gluteal regions. Whether prolonging the duration of therapy will ultimately result in regression of muscular amyloid deposits remains to be seen.6Patient 2 (ATTRwt) complained about lower extremity muscle weakness and muscle cramps, which already started 1-2 years before cardiac manifestation. This was primarily attributed to a side effect of statin therapy. However, it is more likely that these complaints were already due to the subsequently confirmed amyloid myopathy. This is in concurrence with previous reports indicating that amyloid myopathy may precede cardiac manifestation in ATTRwt.It must be noted that ATTR amyloid myopathy is often difficult to distinguish from neuropathy in routine clinical practice. This is particularly because symptoms attributed to amyloid myopathy, such as weakness and cramps, are similar to symptoms of neuropathy, CK levels are mostly within the normal range and changes in EMG are often not very pronounced. This is due to interstitial amyloid localisation, whereas muscle fiber necrosis and muscle fiber alterations, causing changes in CK levels and EMG, are rarely present. Consequently, ATTR amyloid myopathy is likely to be frequently overlooked or mistaken as neuropathy.99mTc-DPD scintigraphy may ultimately be the more important diagnostic screening tool for diagnosis of ATTR amyloid myopathy than biopsy in future, given the current literature.7Histologically remarkable in this case report is the pronounced amyloid deposition in the adipose tissue in both patients, especially in patient 99mTc-labeled-pyrophosphat (99mTc-PYP) was minimal when assessed by qualitative and quantitative metrics. Thus, they conclude that the properties of 99mTc-PYP may be different from 99mTc-DPD in terms of non-cardiac uptake and that 99mTc-PYP cannot be used to image extracardiac ATTR deposition.10In a previous retrospective analysis of 57 patients with cardiac ATTR amyloidosis, Sperry et al noted that skeletal muscle uptake of 99mTc-DPD scintigraphy with high accuracy. As already shown in previous studies, myopathy can precede cardiac manifestation in ATTRwt amyloidosis.6 To date, amyloid myopathy has not been reported in the ATTR-Val40Ile variant and must be recognized as an important contributor to morbidity in these patients. In concurrence with previous reports, our findings from patient 1 (ATTRv) show that neuropathy and cardiomyopathy may precede the initial manifestation of myopathy.6 Whether this also applies to other patients with the ATTR-Val40Ile variant will be subject of future studies.In summary, muscular ATTR deposits can be visualized by 99mTc-DPD scintigraphy enables non-invasive diagnosis of ATTR amyloid myopathy with high accuracy, while invasive muscular biopsy is no longer obligatory. Due to the broad availability of 99mTc-DPD scintigraphy and the emergence of novel therapeutics it is of utmost importance to increase the awareness for the frequent concomitant occurrence of ATTR amyloid cardiomyopathy and myopathy, expanding the clinical spectrum of ATTR amyloidosis.Conclusively, we think that ATTR amyloid myopathy is still underappreciated and underrecognized, because accurate diagnosis in the past seemed difficult to achieve in routine clinical practice. As shown in this case report,


Emotion regulation is crucial in individuals' cognitive ability to manage and express their emotions effectively. This Research Topic delves into the neural processes and reactions associated with emotion regulation using various neurophysiological techniques, including electroencephalogram (EEG), event-related potentials (ERPs), functional magnetic resonance imaging (fMRI), and transcranial electrical stimulation (tES). Furthermore, it investigates the impact of different stimulus types, aesthetic preferences, and mindfulness practices on emotion regulation. The findings contribute to a comprehensive understanding of emotion regulation strategies and provide insights for potential therapeutic interventions.Yang et al.) has proposed distinct roles for the P100, N170, and P250 neural generators. These generators are involved in encoding comprehensive frames of reference, maintaining structural cohesion, and adapting to internal representations of emotional expressions.Within this context, EEG and event-related potentials are valuable tools for investigating the neural processes and reactions related to emotion regulation. A piece of research  component was examined using the mismatch negativity (MMN) in a group of young and middle-aged adults. They employed a modified oddball paradigm to compare responses to standard tones under fearful and neutral facial expressions. The results demonstrated that when exposed to fearful facial expressions, the amplitude of the N1 in response to classic techniques was smaller than in neutral facial expressions.In a study by Additionally, the amplitude was more negative in young adults than middle-aged adults. These findings suggest that the perception of negative emotions visually facilitates the processing of auditory features and enhances acoustic change detection in middle-aged adults. However, this effect cannot compensate for the age-related decline in MMN amplitude.Jamieson et al.).Emotions are interconnected with our social interactions as we navigate the social realm by interpreting and choosing between conflicting emotional cues. The effective face-word Stroop (AFWS) is an experimental method that can help uncover the fundamental neural processes that support crucial social and emotional abilities. Regarding the timing, location, and sequence of control processes involved in responding to emotional conflicts during the AFWS, a study determined that conflict control processes occur within the components of Visually evoked potentials (Åsli and Øvervoll) discovered that the interaction between emotional expressions and model gender influences the magnitude of startle responses. Specifically, greater startle responses were observed when participants viewed angry faces displayed by male models and happy expressions displayed by female models. Another study investigating emotional stimuli in individuals with spinal cord injury  proposed an integrated explanation for emotional conflict resolution during response activation tasks. This study emphasized the influence of emotional arousal and primed approach or avoidance motivation. Furthermore, they discussed the role of arousal in individuals with spinal cord lesions, providing insights into the typical mechanisms involved in emotional conflict control. Understanding emotional conflict control is crucial for adaptive behavior and may have implications for therapeutic interventions.On the other hand, the role of other internal variables has also been addressed. A study utilizing electromyography . Moreover, a study conducted with patients suffering from mild traumatic brain injury examined negative frontal alpha asymmetry using EEG data and found greater right-sided frontal activity than healthy controls .Focusing on the clinical population, results from a study suggested that individuals with Authentic pride (AP) demonstrated greater success in down-regulating negative emotions through cognitive reappraisal, both in daily life and experimental settings, compared to individuals with hubristic pride . The amplitudes of the N400 brain wave component were correlated with participants' level of negative affect during the pre-contemplation stage. Another study revealed that post-error adjustments varied depending on the specific task context.Cognitive appraisal and associated emotional processes were also examined in motivational interviewing  augmented mindfulness, suggesting that regular physical exercise before meditation can enhance early-stage mindfulness. Neurocognitive research indicates that physical exercise (such as aerobic exercises or yoga) and mindfulness impact similar pathways involved in stress regulation and cognitive control, supporting the idea of synergistic effects between physical exercise and mindfulness. Studies focusing on the psychophysiological impact of physical exercise have shown that it can lead to short-term neurocognitive changes that facilitate cognitive control and the attainment of mindful awareness.Mindfulness is another topic covered in this context. Despite the known benefits of mindfulness for mental health, drop-out rates among mindfulness practitioners can occur due to factors such as chronic stress, cognitive reactivity, and pathology. To address this issue, Küçüktaş and St. Jacques, the influence of visual perspective on the emotional aspects of autobiographical memory (AM) retrieval was examined. The review concluded that the impact of visual perspective depends on the emotional nature connected to the event.Lastly, in a review conducted by By investigating the neural correlates and strategies associated with emotion regulation, this research paper aims to advance our understanding of how individuals skillfully handle and display their emotions in various contexts. The multimodal approach provides valuable insights into the underlying processes involved in emotion regulation and informs potential interventions for improving emotional wellbeing and adaptive behavior.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Background: Nonprescription antibiotic use includes taking an antibiotic without medical guidance . Nonprescription use contributes to antimicrobial resistance, adverse drug reactions, interactions, and superinfections such as Clostridioides difficile colitis. Qualitative studies exploring perspectives regarding nonprescription use among Hispanic patients are lacking. We used the Kilbourne Framework for Advancing Health Disparities Research to identify factors influencing Hispanic patients’ nonprescription use and to organize our findings. Methods: Our study includes Hispanic primary-care clinic patients with different types of health coverage in the Houston metroplex who endorsed nonprescription use in a previous quantitative survey. Semistructured interviews explored the factors promoting nonprescription use in Hispanic adults. Interviews were conducted remotely, in English or Spanish, between May 2020 and October 2021. We used inductive coding and thematic analysis to identify the factors and motives for nonprescription use. Results: Of the 35 Hispanic participants surveyed, 69% were female and between the ages of 27 and 66. All participants had some form of healthcare coverage . Participants reported obtaining antibiotics from their own leftover prescriptions and through trusted persons , buying them under the counter in US markets, and purchasing them without a prescription outside the United States. Thematic analysis revealed the factors contributing to nonprescription use . Themes included beliefs that the ‘doctor visit was unnecessary,’ ‘limited direct access to healthcare’ in the United States , ‘more open indirect access to healthcare’ abroad and under the counter in the United States, and communication difficulties . Figure 2 shows representative quotes across thematic domains. Participants expressed having confidence in medical recommendations from pharmacists and trusted community members in their social networks. Conclusions: Antibiotic stewardship interventions that include pharmacist-driven patient education regarding appropriate antibiotic use may decrease nonprescription antibiotic use in Hispanic communities. Additionally, improving access to care while addressing communication barriers and cultural competency in clinics may improve primary care delivery and reduce potentially unsafe antibiotic use.Disclosure: None


Multiple myeloma generally occurs in older adults, with the clonal proliferation of plasma cells and accumulation of monoclonal protein resulting in a broad range of clinical manifestations and complications, including hypercalcemia, renal dysfunction, anaemia, and bone destruction (termed CRAB features). A 64-year-old man with no history of malignancy presented with an enlarging precordial lump occurring three years post-sternotomy for uneventful coronary artery bypass grafting surgery. Initial investigations showed anaemia and impaired renal function. Multimodal imaging performed for further evaluation showcases the radio-pathological features which can be encountered in haematological malignancy. Subsequent percutaneous biopsy confirmed an underlying plasma cell neoplasm, and a diagnosis of multiple myeloma was achieved. The prompt resolution of the lesions upon the initiation of treatment highlights the importance of early diagnosis and treatment.