Supramolecular Control of the Temperature Responsiveness of Fluorescent Macrocyclic Molecular Rotamers.

To fully harness the potential of molecular machines, it is crucial to develop methods by which to exert control over their speed of motion through the application of external stimuli. A conformationally strained macrocyclic fluorescent rotamer, CarROT, displays a reproducible and linear fluorescence decrease towards temperature over the physiological temperature range. Through the external addition of anions, cations or through deprotonation, the compound can access four discreet rotational speeds via supramolecular interactions (very slow, slow, fast and very fast) which in turn stop, reduce or enhance the thermoluminescent properties due to increasing or decreasing non-radiative decay processes, thereby providing a means to externally control the temperature sensitivity of the system. Through comparison with analogues with a higher degree of conformational freedom, the high thermosensitivity of CarROT over the physiological temperature range was determined to be due to conformational strain, which causes a high energy barrier to rotation over this range. Analogues with a higher degree of conformational freedom display lower sensitivities towards temperature over the same temperature range. This study provides an example of an information rich small molecule, in which programable rotational speed states can be observed with facile read-out.

High-throughput homogenous assay for the direct detection of Listeria monocytogenes DNA.

The Amplified Luminescent Proximity Homogenous Assay-linked Immunosorbent Assay (AlphaLISA) is known for detecting various protein targets; however, its ability to detect nucleic acid sequences is not well established. Here, the capabilities of the AlphaLISA technology were expanded to include direct detection of DNA (aka: oligo-Alpha) and was applied to the detection of Listeria monocytogenes. Parameters were defined that allowed the newly developed oligo-Alpha to differentiate L. monocytogenes from other Listeria species through the use of only a single nucleotide polymorphism within the 16S rDNA region. Investigations into the applicability of this assay with different matrices demonstrated its utility in both milk and juice. One remarkable feature of the oligo-Alpha is that greater sensitivity could be achieved through the use of multiple acceptor oligos compared to only a single acceptor oligo, even when only a single donor oligo was employed. Additional acceptor oligos were easily incorporated into the assay and a tenfold change in the detection limit was readily achieved, with detection limits of 250 attomole of target being recorded. In summary, replacement of antibodies with oligonucleotides allows us to take advantage of genotypic difference(s), which both expands its repertoire of biological markers and furthers its use as a diagnostic tool.

Association between number of Adverse Childhood Experiences and depression among older adults is moderated by race.

OBJECTIVE: This study aimed to assess the association between number of Adverse Childhood Experiences (ACE) and history of depression among older adults and to explore the interaction by race. METHODS: This study was a cross-sectional analysis of the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data among 60,122 older respondents (≥ 60 years old). The ACE score (zero, one, two-three, ≥four) included questions assessing exposure to eight types of ACEs before age 18. The outcome was the respondent's self-report depression diagnosed (yes/no). Multivariable logistic regression models examined the association between ACEs and depression stratified by race. Each model adjusted for age, smoking status, income, education, marital status, and body mass index. RESULTS: In this sample of older adults, 47%, 23%, 19% and 10% reported having experienced zero, one, two-three, and four or more types of ACEs, respectively. Depression was reported by 16% of survey respondents. There was a significant interaction between ACE score and race and depression (p = 0.038). Respondents who experienced ≥4 ACEs had higher likelihood of reporting depression for all race/ethnicity groups: non-Hispanic Whites (aOR = 3.83; 95% CI: 3.07, 4.79), non-Hispanic Blacks (aOR = 3.39, 95% CI: 1.71, 6.71), or Hispanics (aOR = 12.61; 95% CI: 4.75, 33.43). This translated to a large effect size for non-Hispanic Whites and Hispanics although the magnitude was bigger for Hispanics. CONCLUSION: The association between number of ACEs and depression was strongest for older adults who identify as Hispanic, but weaker and less consistent for adults who identify as White and Black.

Changes in Gender and Racial/Ethnic Diversity in US Residency Program Applications From 2018 to 2022.

Background Residency application patterns by gender and race/ethnicity offer important insights about diversity in residency recruitment. It is unknown how the COVID-19 pandemic and virtual interviewing affected these patterns. Objective We hypothesized that the introduction of virtual interviews caused an increase in applications submitted per applicant and that there may be differences by gender and race/ethnicity. Methods We extracted publicly reported Electronic Residency Application Service application data from 2018 to 2022 for 14 residency specialties with 1000 or more applicants in 2022 by self-reported gender and underrepresented in medicine (UIM) status. We compared patterns before and after virtual interviews were introduced in 2021. Results Among 401 480 residency applicants, the average number of applications submitted per applicant increased for all specialties between 2018 and 2022 across gender and race/ethnicity. Across all years, women applied to more programs than men in 5 specialties (dermatology, neurology, obstetrics/gynecology, pediatrics, and surgery), whereas men applied to more programs than women in 3 (anesthesia, family medicine, and physical medicine and rehabilitation). Across all years, non-UIM applicants applied to more programs than UIM applicants in all 14 specialties. There were no clear changes in application patterns by gender and race/ethnicity during in-person versus virtual interview years. Conclusions The average number of applications submitted per applicant increased over time across gender and race/ethnicity. In some specialties, women applied to more programs than men, and in others vice-versa, whereas non-UIM applicants applied to more programs than UIM applicants in all specialties. Virtual interviews did not change these patterns.

Analysis of narrative assessments of internal medicine resident performance: are there differences associated with gender or race and ethnicity?

BACKGROUND: Equitable assessment is critical in competency-based medical education. This study explores differences in key characteristics of qualitative assessments (i.e., narrative comments or assessment feedback) of internal medicine postgraduate resident performance associated with gender and race and ethnicity. METHODS: Analysis of narrative comments included in faculty assessments of resident performance from six internal medicine residency programs was conducted. Content analysis was used to assess two key characteristics of comments- valence (overall positive or negative orientation) and specificity (detailed nature and actionability of comment) - via a blinded, multi-analyst approach. Differences in comment valence and specificity with gender and race and ethnicity were assessed using multilevel regression, controlling for multiple covariates including quantitative competency ratings. RESULTS: Data included 3,383 evaluations with narrative comments by 597 faculty of 698 residents, including 45% of comments about women residents and 13.2% about residents who identified with race and ethnicities underrepresented in medicine. Most comments were moderately specific and positive. Comments about women residents were more positive (estimate 0.06, p 0.045) but less specific (estimate - 0.07, p 0.002) compared to men. Women residents were more likely to receive non-specific, weakly specific or no comments (adjusted OR 1.29, p 0.012) and less likely to receive highly specific comments (adjusted OR 0.71, p 0.003) or comments with specific examples of things done well or areas for growth (adjusted OR 0.74, p 0.003) than men. Gendered differences in comment specificity and valence were most notable early in training. Comment specificity and valence did not differ with resident race and ethnicity (specificity: estimate 0.03, p 0.32; valence: estimate - 0.05, p 0.26) or faculty gender (specificity: estimate 0.06, p 0.15; valence: estimate 0.02 p 0.54). CONCLUSION: There were significant differences in the specificity and valence of qualitative assessments associated with resident gender with women receiving more praising but less specific and actionable comments. This suggests a lost opportunity for well-rounded assessment feedback to the disadvantage of women.

Use of Complementary and Integrative Medicine for Alzheimer's Disease and Cognitive Decline.

Integrative medicine takes a holistic approach because it considers multiple aspects of the individual. This includes a person's physical, emotional, interpersonal, behavioral, nutritional, environmental, and spiritual dimensions of wellbeing that contribute to the Whole Person Health. There is increasing interest and popularity of integrative approaches to treating cognitive decline and dementia because of the multifactorial nature of aging and the limited pharmacological interventions available in treating cognitive decline and dementia, particularly Alzheimer's disease, the most common type of dementia. This review summarizes the existing evidence using complementary and integrative medicine therapies in cognitive decline and Alzheimer's disease. This includes the use of mind-body therapies, lifestyle interventions (nutritional, physical exercise, stress reduction), and other integrative modalities. Unfortunately, there are still limited studies available to guide clinicians despite the increasing popularity of integrative treatments.

Factors Associated with Venous Thromboembolism Development in Patients with Traumatic Brain Injury.

BACKGROUND: Venous thromboembolic (VTE) events are a major concern in trauma and intensive care, with the prothrombotic state caused by traumatic brain injury (TBI) increasing the risk in affected patients. We sought to identify critical demographic and clinical variables and determine their influence on subsequent VTE development in patients with TBI. METHODS: This was a cross-sectional study with data retrospectively collected from 818 patients with TBI admitted to a level I trauma center in 2015-2020 and placed on VTE prophylaxis. RESULTS: The overall VTE incidence was 9.1% (7.6% deep vein thrombosis, 3.2% pulmonary embolism, 1.7% both). The median time to diagnosis was 7 days (interquartile range 4-11) for deep vein thrombosis and 5 days (interquartile range 3-12) for pulmonary embolism. Compared with those who did not develop VTE, patients who developed VTE were younger (44 vs. 54 years, p = 0.02), had more severe injury (Glasgow Coma Scale 7.5 vs. 14, p = 0.002, Injury Severity Score 27 vs. 21, p < 0.001), were more likely to have experienced polytrauma (55.4% vs. 34.0%, p < 0.001), more often required neurosurgical intervention (45.9% vs. 30.5%, p = 0.007), more frequently missed ≥ 1 dose of VTE prophylaxis (39.2% vs. 28.4%, p = 0.04), and were more likely to have had a history of VTE (14.9% vs. 6.5%, p = 0.008). Univariate analysis demonstrated that 4-6 total missed doses predicted the highest VTE risk (odds ratio 4.08, 95% confidence interval 1.53-10.86, p = 0.005). CONCLUSIONS: Our study highlights patient-specific factors that are associated with VTE development in a cohort of patients with TBI. Although many of these are unmodifiable patient characteristics, a threshold of four missed doses of chemoprophylaxis may be particularly important in this critical patient population because it can be controlled by the care team. Development of intrainstitutional protocols and tools within the electronic medical record to avoid missed doses, particularly among patients who require operative interventions, may result in decreasing the likelihood of future VTE formation.

'Who you gonna call?' A qualitative study of psychiatrists accessing mental health services.

OBJECTIVE: To identify motivation, capabilities and opportunities that enable psychiatrists and registrars to seek help for mental health problems and to inform design of interventions. METHOD: Data collected in qualitative semi-structured interviews were analysed using a framework approach with the COM-B model of behaviour as a theoretical frame. RESULTS: Accounts of the eight participants show help-seeking to be a complex process requiring cognitive and emotional capability to recognise a problem or goal, acceptance of vulnerability, and facilitated by access to professional networks. Help-seeking was enabled by openness about mental health problems in workplace culture. CONCLUSIONS: Interventions to enable help-seeking should focus on normalising the experience of mental health problems among doctors and challenge the notion that difficulties represent characterological flaws. Greater understanding of the mandatory reporting requirements is also required.

Exploring gender and thematic differences in qualitative assessments of internal medicine resident performance.

INTRODUCTION: Evidence suggests gender disparities in medical education assessment, including differences in ratings of competency and narrative comments provided in resident performance assessments. This study explores how gender manifests within the content of qualitative assessments (i.e., narrative comments or performance feedback) of resident performance. METHODS: Qualitative content analysis was used to explore gender-based differences in narrative comments included in faculty assessments of resident performance during inpatient medicine rotations at six Internal Medicine residency programs, 2016-2017. A blinded, multi-analyst approach was employed to identify themes across comments. Patterns in themes with resident gender and post-graduate year (PGY) were explored, focusing on PGY2 and PGY3 when residents are serving in the team leader role. RESULTS: Data included 3,383 evaluations with narrative comments of 385 men (55.2%) and 313 women residents (44.8%). There were thematic differences in narrative comments received by men and women residents and how these themes manifested within comments changed with training time. Compared to men, comments about women had a persistent relationship-orientation and emphasized confidence over training including as interns and in PGY2 and PGY3, when serving as team leader. The relationship-orientation was characterized not only by the residents' communal attributes but also their interpersonal and communication skills, including efforts supporting others and establishing the tone for the team. Comments about women residents often highlighted confidence, including recommendations around behaviors that convey confidence in decision-making and team leadership. DISCUSSION: There were gender-based thematic differences in qualitative assessments. Comments about women resident team leaders highlight relationship building skills and urge confidence and actions that convey confidence as team leader. Persistent attention to communal skills suggests gendered expectations for women resident team leaders and a lost opportunity for well-rounded feedback to the disadvantage of women residents. These findings may inform interventions to promote equitable assessment, such as providing feedback across the competencies.

Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis.

Genes involved in synaptic function are enriched among those with autism spectrum disorder (ASD)-associated rare genetic variants. Dysregulated cortical neurogenesis has been implicated as a convergent mechanism in ASD pathophysiology, yet it remains unknown how 'synaptic' ASD risk genes contribute to these phenotypes, which arise before synaptogenesis. Here, we show that the synaptic Ras GTPase-activating (RASGAP) protein 1 (SYNGAP1, a top ASD risk gene) is expressed within the apical domain of human radial glia cells (hRGCs). In a human cortical organoid model of SYNGAP1 haploinsufficiency, we find dysregulated cytoskeletal dynamics that impair the scaffolding and division plane of hRGCs, resulting in disrupted lamination and accelerated maturation of cortical projection neurons. Additionally, we confirmed an imbalance in the ratio of progenitors to neurons in a mouse model of Syngap1 haploinsufficiency. Thus, SYNGAP1-related brain disorders may arise through non-synaptic mechanisms, highlighting the need to study genes associated with neurodevelopmental disorders (NDDs) in diverse human cell types and developmental stages.

A Mediterranean-Style Diet Improves the Parameters for the Management and Prevention of Type 2 Diabetes Mellitus.

Background and Objectives: Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors, such as prediabetes and obesity, increasing each year, the need to address risk factor reduction strategies is crucial. Materials and Methods: Twenty-two men and women, overweight-to-obese adults (BMI mean: 26.1-31.6) (age range mean: 44.6-51.8) with T2DM, indicators of prediabetes, or who were metabolically healthy, participated in Cal Poly's Nutrition and Exercise in Type 2 Diabetes (CPNET) study. There were no significant differences in terms of age, BMI, or sex distribution among the groups at the baseline. This study's protocol included following a Mediterranean-style diet, the daily consumption of a high-quality whey protein supplement, and physical activity recommendations for 16 weeks. Body composition data, via dual-energy X-ray absorptiometry (DXA), and fasting blood samples were collected at the baseline and following the intervention. Due to restrictions associated with the outbreak of the COVID-19 pandemic, only 13 of the 22 participants who started this study were able to return for the second data collection to complete this study following the 16-week intervention. Results: The prediabetic and T2DM groups exhibited reductions in their fasting plasma glucose (12.0 mg/dL reduction in the prediabetic group; 19.6 mg/dL reduction in the T2DM group) to that of normal and prediabetic levels, respectively, while the T2DM group also demonstrated improvement in their hemoglobin A1c (reduced from 6.8% to 6.0%) to prediabetic levels. Additionally, the metabolically healthy, overweight group exhibited significant improvements in adiposity, while the obese prediabetic and T2DM groups showed non-significant improvements in all the measured metrics of body composition. No significant changes were observed in the inflammatory biomarkers (p-values ranged from 0.395 to 0.877). Conclusions: Collectively, our results suggest that adherence to a well-balanced, nutritious diet and activity may improve the parameters of glycemic control and provide benefits to body composition that help to manage and prevent the development of T2DM. Our study was able to yield significant findings signifying that the effects of a Mediterranean-style diet are observed even for a more conservative sample size.

Impact of premorbid oral anticoagulant use on survival in patients with traumatic intracranial hemorrhage.

OBJECTIVE: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation. METHODS: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis. RESULTS: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001). CONCLUSIONS: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

Academic Leadership Academy Summer Program: Clerkship Transition Preparation for Underrepresented in Medicine Medical Students.

PROBLEM: Enhancing workforce diversity by increasing the recruitment of students who have been historically excluded/underrepresented in medicine (UIM) is critical to addressing healthcare inequities. However, these efforts are inadequate when undertaken without also supporting students' success. The transition to clerkships is an important and often difficult to navigate inflection point in medical training where attention to the specific needs of UIM students is critical. INTERVENTION: We describe the design, delivery, and three-year evaluation outcomes of a strengths-based program for UIM second year medical students. The program emphasizes three content areas: clinical presentations/clinical reasoning, community building, and surfacing the hidden curriculum. Students are taught and mentored by faculty, residents, and senior students from UIM backgrounds, creating a supportive space for learning. CONTEXT: The program is offered to all UIM medical students; the centerpiece of the program is an intensive four-day curriculum just before the start of students' second year. Program evaluation with participant focus groups utilized an anti-deficit approach by looking to students as experts in their own learning. During focus groups mid-way through clerkships, students reflected on the program and identified which elements were most helpful to their clerkship transition as well as areas for programmatic improvement. IMPACT: Students valued key clinical skills learning prior to clerkships, anticipatory guidance on the professional landscape, solidarity and learning with other UIM students and faculty, and the creation of a community of peers. Students noted increased confidence, self-efficacy and comfort when starting clerkships. LESSONS LEARNED: There is power in learning in a community connected by shared identities and grounded in the strengths of UIM learners, particularly when discussing aspects of the hidden curriculum in clerkships and sharing specific challenges and strategies for success relevant to UIM learners. We learned that while students found unique benefits to preparing for clerkships in a community of UIM students, near peers, and faculty, future programs could be enhanced by pairing this formal intensive curriculum with more longitudinal opportunities for community building, mentoring, and career guidance.

Selective and deceptive citation in the construction of dueling consensuses.

The COVID-19 pandemic provides a unique opportunity to study science communication and, in particular, the transmission of consensus. In this study, we show how "science communicators," writ large to include both mainstream science journalists and practiced conspiracy theorists, transform scientific evidence into two dueling consensuses using the effectiveness of masks as a case study. We do this by compiling one of the largest, hand-coded citation datasets of cross-medium science communication, derived from 5 million Twitter posts of people discussing masks. We find that science communicators selectively uplift certain published works while denigrating others to create bodies of evidence that support and oppose masks, respectively. Anti-mask communicators in particular often use selective and deceptive quotation of scientific work and criticize opposing science more than pro-mask communicators. Our findings have implications for scientists, science communicators, and scientific publishers, whose systems of sharing (and correcting) knowledge are highly vulnerable to what we term adversarial science communication.

Understanding the Unique Challenges Faced by Homeless Patients With Acute Traumatic Neurosurgical Injuries.

BACKGROUND: Homelessness is associated with high risk of acute neurotraumatic injury in the ∼600 000 Americans affected on any given night. OBJECTIVE: To compare care patterns and outcomes between homeless and nonhomeless individuals with acute neurotraumatic injuries. METHODS: Adults hospitalized for acute neurotraumatic injuries between January 1, 2015, and December 31, 2020, were identified in this retrospective cross-sectional study at our Level 1 trauma center. We evaluated demographics, in-hospital characteristics, discharge dispositions, readmissions, and adjusted readmission risk. RESULTS: Of 1308 patients, 8.5% (n = 111) were homeless on admission to neurointensive care. Compared with nonhomeless individuals, homeless patients were younger ( P = .004), predominantly male ( P = .003), and less frail ( P = .003) but had similar presenting Glasgow Coma Scale scores ( P = .85), neurointensive care unit stay time ( P = .15), neurosurgical interventions ( P = .27), and in-hospital mortality ( P = .17). Nevertheless, homeless patients had longer hospital stays (11.8 vs 10.0 days, P = .02), more unplanned readmissions (15.3% vs 4.8%, P < .001), and more complications while hospitalized (54.1% vs 35.8%, P = .01), particularly myocardial infarctions (9.0% vs 1.3%, P < .001). Homeless patients were mainly discharged to their previous living situation (46.8%). Readmissions were primarily for acute-on-chronic intracranial hematomas (4.5%). Homelessness was an independent predictor of 30-day unplanned readmissions (odds ratio 2.41 [95% CI 1.33-4.38, P = .004]). CONCLUSION: Homeless individuals experience longer hospital stays, more inpatient complications such as myocardial infarction, and more unplanned readmissions after discharge compared with their housed counterparts. These findings combined with limited discharge options in the homeless population indicate that better guidance is needed to improve the postoperative disposition and long-term care of this vulnerable patient population.

O-Arm Accuracy and Radiation Exposure in Adult Deformity Surgery.

OBJECTIVE: In long thoracolumbar deformity surgery, accurate screw positioning is critical for spinal stability. We assessed pedicle and pelvic screw accuracy and radiation exposure in patients undergoing long thoracolumbar deformity fusion surgery (≥4 levels) involving 3-dimensional fluoroscopy (O-Arm/Stealth) navigation. METHODS: In this retrospective single-center cohort study, all patients aged >18 years who underwent fusion in 2016-2018 were reviewed. O-Arm images were assessed for screw accuracy. Effective radiation doses were calculated. The primary outcome was pedicle screw accuracy (Heary grade). Secondary outcomes were pelvic fixation screw accuracy, radiation exposure, and screw-related perioperative and postoperative complications or revision surgery within 3 years. RESULTS: Of 1477 pedicle screws placed in 91 patients (mean 16.41 ± 5.6 screws/patient), 1208 pedicle screws (81.8%) could be evaluated by 3-dimensional imaging after placement. Heary Grade I placement was achieved in 1150 screws (95.2%), Grade II in 47 (3.9%), Grade III in 10 (0.82%), Grade IV in 1 (0.08%), and Grade V in 0; Grade III-V were replaced intraoperatively. One of 60 (1.6%) sacroiliac screws placed showed medial cortical breach and was replaced. The average O-Arm-related effective dose was 29.54 ± 14.29 mSv and effective dose/spin was 8.25 ± 2.65 mSv. No postoperative neurological worsening, vascular injuries, or revision surgeries for screw misplacement were recorded. CONCLUSIONS: With effective radiation doses similar to those in interventional neuroendovascular procedures, the use of O-Arm in multilevel complex deformity surgery resulted in high screw accuracy, no need for surgical revision because of screw malposition, less additional imaging, and no radiation exposure for the surgical team.