Problem Sexual Behavior and Engagement in Therapeutic Intervention among Children Aged 4-12.

Early intervention in problem sexual behavior (PSB) is critical; however, little is known about the engagement of children and families in therapeutic intervention for PSB. This research explored the characteristics, presenting issues, and engagement of 242 children aged 4-12 years attending a therapeutic service for PSB. Most frequently, PSB occurred within sibling relationships. Girls were more likely to engage in PSB alone (self-directed or non-targeted behaviors), while boys were more likely to involve other young people (interpersonal PSB). One-third (35%) of clients engaged in completion of therapy. Parental noninvolvement and self-directed or non-targeted PSB predicted early disengagement. Client demographics, sexual abuse, and interpersonal sexual behaviors were not associated with therapy completion. Implications for therapeutic intervention in children's PSB are discussed.

Sonic hedgehog suppresses penile remodeling after cavernous nerve injury and sustains long-term normal penis morphology.

BACKGROUND: Cavernous nerve (CN) injury, which occurs in prostatectomy and diabetic cases, initiates penile remodeling, including smooth muscle apoptosis and increased collagen in the corpora cavernosa, which are underlying causes of erectile dysfunction. Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and SHH treatment suppresses corpora cavernosa remodeling that occurs with CN injury. AIM: We examine if SHH treatment by peptide amphiphile (PA) in the first week after CN injury is sufficient to prevent long-term penis remodeling and if apoptosis inhibitors also suppress penile remodeling. METHODS: Bilateral CN crush was performed on adult Sprague-Dawley rats (P115-120) that underwent 1 of 3 treatments with novel extended-release nanofiber PA hydrogels for delivery: SHH protein (n = 10), mouse serum albumin protein (control, n = 7), or caspase 3 inhibitor (AC-DEVD-CHO, n = 10). Rats were sacrificed after 18 to 24 days. Additional rats underwent CN injury (n = 6) or CN injury and SHH PA treatment for 2 and 4 days (n = 8) and included sham controls (n = 3) and nonsurgery controls (n = 3). OUTCOMES: Trichrome stain, hydroxyproline assay, and Western analysis for α-actin (smooth muscle) and GAPDH were performed to examine smooth muscle retention and collagen abundance. RESULTS: Smooth muscle decreased with CN injury. Corpora cavernosa showed increased smooth muscle at 2, 4, and 24 days after CN injury with SHH PA treatment in comparison with mouse serum albumin treatment among CN-injured controls. Caspase 3-inhibited penis demonstrated little smooth muscle preservation. Collagen was decreased 23% with SHH PA treatment (P < .001) at 18 to 24 days after CN injury. Collagen was unchanged with caspase 3 inhibitor treatment (P > .99). CLINICAL TRANSLATION: It is important to know that treatments given at the time of CN injury have a sustained effect on preserving penile architecture and thus erectile function, making them valuable for clinical translation. STRENGTHS AND LIMITATIONS: SHH PA treatment preserves penile smooth muscle after CN injury. Time points past 24 days were not examined, although penile remodeling takes place acutely after CN injury. Measurement of erectile function was not examined. CONCLUSIONS: SHH treatment by PA in the first week after CN injury is sufficient to suppress penile remodeling and to preserve penile smooth muscle over time, which is critical to prevent development of erectile dysfunction. There is a difference in the corpora cavernosa smooth muscle from proximal to distal in the penis of the Sprague-Dawley rat model. It is critical when examining therapy efficacy to ensure that comparable regions of the penis are analyzed. STATEMENT OF SIGNIFICANCE: In this study, we examine if suppression of apoptosis in penile smooth muscle in the first week after cavernous nerve injury is sufficient to preserve smooth muscle long-term.

Narratives of Actionable Medical Leadership From Senior Leaders for Aspiring Leaders in Academic Medicine.

Background: Physicians understand that certain personal attributes are essential in medical leaders, but they often do not know what actions are expected of them as leaders or what they should do to be more effective leaders. Purpose: We sought to compile, through interviews with senior leaders at an academic institution, real leadership scenarios for a series of case-based examples to be used during group mentoring sessions for aspiring medical leaders. Methods: We conducted one-to-one interviews using open-ended questions with 11 current and emeritus chairpersons or chiefs of major departments or divisions at our academic medical center. Questions were designed to elicit anecdotes and examples of actions that demonstrate effective and ineffective leadership. Responses were analyzed with qualitative techniques to generate topics of leadership behaviors, which then were compiled into a collection of illustrative examples. Results: The leaders interviewed discussed challenges they encountered in daily routines and described how they addressed certain dilemmas. Topics included making decisions without complete information, winning over reluctant administrators, building alliances with peers, involving subordinates in initiatives, and using knowledge to defend one's position. Actions requiring interpersonal skills also were discussed, including varying modes of communication, avoiding adversity, displaying gratitude toward subordinates, and safeguarding one's professional image. The leaders' insights and recommendations were compiled into a themed collection of topics to be used during group mentoring sessions to enhance leadership skills. Conclusions: This qualitative study suggests that the wisdom and experience of senior leaders may be gleaned for a collection of case-based topics that could complement other formal training programs for aspiring medical leaders.

Evaluation of Turnaround Times for Antigen Testing in Hospitalized Patients With Histoplasmosis and Blastomycosis.

Review of histoplasmosis and blastomycosis antigen testing for 39 patients hospitalized with these diseases found that there were significantly longer turnaround times between the time of specimen collection and receipt of positive test results among those patients who had worse outcomes.

Development of Microcystoid Macular Degeneration in the Retina of Nonhuman Primates: Time-Course and Associated Pathologies.

PURPOSE: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it. METHODS: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. In vivo imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy. RESULTS: MMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2 weeks following the RNFL loss. CONCLUSION: These data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity per se in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.

Human Alzheimer's Disease ATN/ABC Staging Applied to Aging Rhesus Macaque Brains: Association With Cognition and MRI-Based Regional Gray Matter Volume.

The brain changes of Alzheimer's disease (AD) include Abeta (Aß) amyloid plaques ("A"), abnormally phosphorylated tau tangles ("T"), and neurodegeneration ("N"). These have been used to construct in vivo and postmortem diagnostic and staging classifications for evaluating the spectrum of AD in the "ATN" and "ABC" ("B" for Braak tau stage, "C" for Consortium to Establish a Registry for Alzheimer's Disease [CERAD] neuritic plaque density) systems. Another common AD feature involves cerebral amyloid angiopathy (CAA). We report the first experiment to examine relationships among cognition, brain distribution of amyloid plaques, CAA, tau/tangles, and magnetic resonance imaging (MRI)-determined volume changes (as a measure of "N") in the same group of behaviorally characterized nonhuman primates. Both ATN and ABC systems were applied to a group of 32 rhesus macaques aged between 7 and 33 years. When an immunohistochemical method for "T" and "B" was used, some monkeys were "triple positive" on ATN, with a maximum ABC status of A1B2C3. With silver or thioflavin S methods, however, all monkeys were classified as T-negative and B0, indicating the absence of mature neurofibrillary tangles (NFTs) and hence neuropathologically defined AD. Although monkeys at extremes of the ATN and ABC classifications, or with frequent CAA, had significantly lower scores on some cognitive tests, the lack of fully mature NFTs or dementia-consistent cognitive impairment indicates that fully developed AD may not occur in rhesus macaques. There were sex differences noted in the types of histopathology present, and only CAA was significantly related to gray matter volume.

How Safe Are COVID-19 Vaccines in Individuals with Immune-Mediated Inflammatory Diseases? The SUCCEED Study.

We were tasked by Canada's COVID-19 Immunity Task Force to describe severe adverse events (SAEs) associated with emergency department (ED) visits and/or hospitalizations in individuals with immune-mediated inflammatory diseases (IMIDs). At eight Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; the mean age was 52.5 years. The BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. A total of 49% of participants had IBD, 27.4% had RA, 14.3% had PsA, 5.3% had SpA, and 4% had SLE. Twelve (0.77% of 1556 participants) SAEs leading to an ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included six (0.39% of 1556 participants) ED visits (including one due to Bell's Palsy 31 days after first vaccination) and six (0.39% of 1556 participants) hospitalizations (including one due to Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs included pericarditis, one involved SLE (considered a serious disease flare), and one involved RA. Thus, in the 31 days after SARS-CoV-2 vaccination in our IMID sample, very few serious adverse events occurred. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab's results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

Dative Bonding in Quasimetallatranes Containing Group 15 Donors (Y = N, P, and As) and Group 14 Acceptors (M = Si, Ge, Sn, and Pb).

Metallatranes and their analogous fused ring [3.3.0] bicyclic compounds, quasimetallatranes, have emerged as fascinating molecular systems with intriguing structural, bonding, and conformational properties. We present a comprehensive investigation aimed at unraveling the nature of dative bonding and exploring the conformational flexibility of these compounds. We extensively characterize the dative bond between the metal center and the electron pair donor, using a range of modeling techniques. Our analyses involve structural optimizations, molecular orbital examinations, and covalency ratio calculations, which provide a thorough understanding of the bonding interactions responsible for the stability of these systems. The results confirmed the presence of dative bonds, supported by the close proximity between the metal and the electron-donating group, and the observation of overlapping electron density. Our studies reveal a correlation between the size of the electron-donor and the coordinating metal atom, and the strength of the dative interaction, as indicated by the bond length and the Wiberg bond indices. This bond strength, in turn, influences the conformational preferences adopted by these compounds. This investigation sheds light on the fundamental aspects of the fused ring [3.3.0] bicyclic quasimetallatrane compounds and offers valuable insights into their unique properties.

Correction of a widespread bias in pooled chemical genomics screens improves their interpretability.

Chemical genomics is a powerful and increasingly accessible technique to probe gene function, gene-gene interactions, and antibiotic synergies and antagonisms. Indeed, multiple large-scale pooled datasets in diverse organisms have been published. Here, we identify an artifact arising from uncorrected differences in the number of cell doublings between experiments within such datasets. We demonstrate that this artifact is widespread, show how it causes spurious gene-gene and drug-drug correlations, and present a simple but effective post hoc method for removing its effects. Using several published datasets, we demonstrate that this correction removes spurious correlations between genes and conditions, improving data interpretability and revealing new biological insights. Finally, we determine experimental factors that predispose a dataset for this artifact and suggest a set of experimental and computational guidelines for performing pooled chemical genomics experiments that will maximize the potential of this powerful technique.

Multireference Averaged Quadratic Coupled Cluster (MR-AQCC) Study of the Geometries and Energies for ortho-, meta- and para-Benzyne.

The diradical benzyne isomers are excellent prototypes for evaluating the ability of an electronic structure method to describe static and dynamic correlation. The benzyne isomers are also interesting molecules with which to study the fundamentals of through-space and through-bond diradical coupling that is important in so many electronic device applications. In the current study, we utilize the multireference methods MC-SCF, MR-CISD, MR-CISD+Q, and MR-AQCC with an (8,8) complete active space that includes the σ, σ*, π and π* orbitals, to characterize the electronic structure of ortho-, meta- and para-benzyne. We also determine the adiabatic and vertical singlet-triplet splittings for these isomers. MR-AQCC and MR-CISD+Q produced energy gaps in good agreement with previously obtained experimental values. Geometries, orbital energies and unpaired electron densities show significant through-space coupling in the o- and m-benzynes, while p-benzyne shows through-bond coupling, explaining the dramatically different singlet-triplet gaps between the three isomers.

The disaggregation of the oswestry disability index in patients undergoing lumbar surgery for degenerative lumbar spondylolisthesis.

BACKGROUND CONTEXT: The Oswestry Disability Index (ODI), is a widely used patient-reported outcome measure (PROM) for assessing functional status in individuals with lumbar spine pathology. The ODI is used by surgeons to determine the initial status and monitor progress after surgery. Compiled ODI data enables comparisons between different surgical techniques. Degenerative lumbar spondylolisthesis (DLS) often causes symptoms such as back pain and neurogenic claudication affecting quality of life and activities of daily living captured by the ODI. Despite extensive studies on ODI changes after spinal surgery, little is known about the characteristics and changes in the different ODI subsections. PURPOSE: To analyze the baseline characteristics and changes in total ODI and ODI subsections 2 years after elective lumbar surgery. STUDY DESIGN: Retrospective analysis on patients prospectively enrolled who underwent spinal surgery for degenerative lumbar spondylolisthesis from 2016 to 2018. The ODI was assessed preoperatively and 2 years postoperatively. PATIENT SAMPLE: A total of 265 patients were included in the study, 60% were female. The mean age of the patients was 67±8 years, and the mean BMI was 30±6 kg/m2. OUTCOME MEASURES: The analysis considered the differences in ODI scores before and after surgery, as well as the changes in all ODI subsections 2 years after elective lumbar surgery for DLS. METHODS: The analysis evaluated differences in ODI scores and variations in different subsections. Patients without an ODI follow-up at 2 years were excluded from the study. The study utilized the Wilcoxon Signed Rank Test for all prepost paired samples. The Wilcoxon rank sum test was used for sex and procedure comparisons for overall ODI and ODI subsection analysis. Univariate linear regression was applied for overall and subsection specific ODI outcomes with age and BMI as independent variables, respectively. The statistical significance level was set at p<.05. RESULTS: Improvement in ODI was observed in 242 patients (91%). The highest baseline disability values were found for the questions regarding pain intensity (3.4±1.3), lifting (3.2±1.9), and standing (3.4±1.3). The lowest preoperative functional limitations were observed in sleeping (1.6±1.3), personal care (1.6±1.4), traveling (1.6±1.2) and sitting (1.5±1.4). At the 2-year follow-up, there was significant improvement in all questions and the overall ODI (all p<.001). The ODI subsections that showed the greatest absolute improvements were changing degree of pain (-2.6), with 89% of patients experiencing improvement, standing (-2.4) with 87% of patients experiencing improvement, and pain intensity (-2.1) with 81% of patients experiencing improvement. The subsections with the least improvement were personal care (-0.6), sitting (-0.7), and sleeping (-0.9). The study found that female patients had a significantly higher preoperative disability in various subsections but showed greater improvement in total ODI compared to male patients (p=.001). Additionally, improvement in sitting (p<.001), traveling (p<.001), social life (p<.001) and sleeping (p=.018) were significantly higher in female patients. Older patients showed significantly less improvement in sitting (p=.005) and sleeping (p=.002). A higher BMI was significantly associated with less improvement in changing degree of pain (p=.025) and higher baseline disability in various subsections. Patients who underwent decompression and fusion had significantly higher baseline disability in several subsections compared to those who underwent decompression alone. There was no significant difference between decompression alone and decompression with fusion in terms of overall improvement in the ODI and improvement in the subsections. CONCLUSION: These results offer a more comprehensive understanding of ODI and its changes across different subsections. This insight is invaluable for improving preoperative education and effectively managing patient expectations regarding potential postsurgery disability in specific areas.

Maintenance of CPR skills among nursing students trained using Resuscitation Quality Improvement® program.

Background: The Resuscitation Quality Improvement® (RQI) program is a competency-based approach that provides low dose, high frequency cardiopulmonary resuscitation (CPR) skills training. Limited research has evaluated its effectiveness with nursing students who need to be prepared to respond to cardiopulmonary emergencies despite their student status and to be competent in CPR as they transition into practice. Objective: The objective of this multisite longitudinal study was to examine the maintenance of adult and infant compressions and ventilation skills by nursing students at 3 and 6 months following practice with real-time feedback using the RQI® program. Methods: The effectiveness of brief practice of CPR skills at the RQI® simulation station on the maintenance of skills was analyzed with 238 nursing students from six universities across the United States. Participants completed three practice sessions, at baseline (month 0), 3 months, and 6 months. At baseline, they performed compressions and ventilation with a bag-valve mask on adult and infant manikins without feedback (pretest), followed immediately by a session integrating real-time, objective feedback (both audio and visual) on their performance. CPR practice on the manikins with feedback on performance was then repeated every 3 months. Results: Practicing CPR skills at the RQI® simulation station every 3 months with real-time feedback enabled participants to maintain their compression and ventilation skills and improve them from baseline (month 0) to 6 months. There was no loss of skills among these participants. Median scores on the first attempt to compress and ventilate stayed above the minimum 75 % overall score that learners must achieve to be considered an adequate performance. Conclusions: This study demonstrated that brief practice of CPR skills at the RQI® simulation station every 3 months with real-time feedback was highly effective for maintaining students' competence in compressions and ventilation. Once the RQI® program is set up in a school, students could practice on their own as needed to maintain their skills.

The spinopelvic alignment in patients with prior knee or hip arthroplasty undergoing elective lumbar surgery.

BACKGROUND CONTEXT: Concurrent degeneration of the lumbar spine, hip, and knee can cause significant disability and lower quality of life. Osteoarthritis in the lower extremities can lead to movement limitations, possibly requiring total knee arthroplasty (TKA) or total hip arthroplasty (THA). These procedures often impact spinal posture, causing alterations in spinopelvic alignment and lumbar spine degeneration. It is unclear if patients with a history of prior total joint arthroplasty (TJA) have different spinopelvic alignment compared to patients without. PURPOSE: To assess the relationship between a history of previous THA or TKA, as well as combined THA and TKA, and the spinopelvic alignment in patients undergoing elective lumbar surgery for degenerative conditions. STUDY DESIGN: A retrospective analysis was conducted on patients who underwent lumbar surgery for degenerative conditions. The patients were stratified based on a history of TKA, THA, or both TKA and THA. PATIENT SAMPLE: A total of 632 patients (63% female) with an average age of 64±11 years and an average BMI of 30±6 kg/m2 were included. OUTCOME MEASURES: Patients were stratified based on a history of THA, TKA, or combined THA and TKA. Spinopelvic parameters (lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI)) were assessed. The relationship between spinopelvic alignment and prior TKA, THA or TKA and THA was analyzed METHODS: The data was tested for normal distribution using the Shapiro-Wilk test. We analyzed the relationship between the spinopelvic parameters and the different arthroplasty groups. Differences in scores between groups were examined using ANOVA. Tukey's Honestly Significant Difference test was used for pairwise comparison for significant ANOVA test results. Multivariable linear regression was applied, adjusted for age, sex and BMI. RESULTS: A total of 632 patients (63% female) were included in the study. Of these patients, 74 (12%) had a history of isolated TKA, 40 (6%) had prior isolated THA, and 15 (2%) had TKA and THA prior to lumbar surgery. Patients with prior arthroplasty were predominantly female (59%) and significantly older (68±7 years vs. 63±12 years, p<.001) with a significantly higher BMI (31±6 kg/m2 vs. 29±6 kg/m2, p<.001). The LL was significantly lower (45.0°±13 vs. 50.9°±14 p=.011) in the arthroplasty group compared to the nonarthroplasty group. A history of isolated TKA was significantly associated with lower LL (Est=-3.8, 95% CI -7.3 to -0.3, p=.031) and SS (Est=-2.6, 95% CI -5.0 to -0.2, p=.012) compared to patients without TJA. Prior combined THA and TKA was found to be significantly associated with a higher PT compared to the nonarthroplasty group (Est=5.1, 95% CI 0.4-9.8, p=.034). CONCLUSION: The spinopelvic alignment differs between patients with and without prior TJA who undergo elective lumbar surgery. The study shows that a history of TKA is significantly associated with a lower LL and SS. The combination of THA and TKA was associated with a significantly higher PT. These findings highlight the complex relationship between the hip, spine, and knee. Moreover, the results could aid in enhancing preoperative planning of lumbar surgery in patients with known TJA.

Optimization of self- or parent-reported psychiatric phenotypes in longitudinal studies.

BACKGROUND: The Adolescent Brain Cognitive Development (ABCD) study is a longitudinal study of US adolescents with a wide breadth of psychiatric, neuroimaging and genetic data that can be leveraged to better understand psychiatric diseases. The reliability and validity of the psychiatric data collected have not yet been examined. This study aims to explore and optimize the reliability/validity of psychiatric diagnostic constructs in the ABCD study. METHODS: Parent-and-child-reported psychiatric data for 11,876 children (aged 9.5 ± 0.5 at first assessment) were examined over 4 years to derive specific constructs for psychiatric diagnoses using longitudinal information. Rates of psychiatric disorders were calculated and compared to those reported in the epidemiological literature. RESULTS: The rates of self-reported psychiatric disorders at any single time point (broad diagnostic construct) were higher than indicated by epidemiological studies. Narrow diagnostic constructs, which required the endorsement of psychiatric disorders at a majority of longitudinal assessments, demonstrated a better rate approximation of literature-reported prevalences for most disorders (e.g. the prevalence of broad obsessive-compulsive disorder (OCD) was 13.3% compared to narrow OCD at 2.6% and a literature-reported prevalence of 2.3%). Analysis of comorbidity, using OCD as a representative example, also showed a better approximation of literature-reported comorbidity rates using the narrow construct, with some exceptions. CONCLUSIONS: Self- or parent-report-based assessments tend to overestimate prevalences of psychiatric disorders in the ABCD Study, particularly when longitudinal data are summed to create lifetime prevalences. Such assessments should be accompanied by more in-depth assessments or clinician-administered structured interviews if using data where accurate disorder classifications are paramount.

Skin mycosis distribution, and burden of visits over a decade in Colombia: ecological study.

Objectives: To describe the sociodemographic distribution of dermatomycosis and the visits burden over a 10-year period of care. Methods: An ecological study was conducted using data on visits and people treated in the Colombian Health System during 2010-2019 using the International Classification of Diseases, Tenth Revision codes (ICD-10). Departments and geopolitical regions were the units of analysis, and visit burden was reported as frequency, intensity (visits per person), and rate of dermatomycosis visits (per 10,000 visits; 95% confidence interval). Results: A total of 4,570,593 visits were analyzed. The most used ICD-10 codes were B369 (superficial mycosis, unspecified), B360 (pityriasis versicolor), B354 (Tinea corporis), B359 (dermatophytosis), and B351 (Tinea unguium) (56.5%), with visits primarily involving the adult population (27-59 years; 32.2%), women (43.4%), and urban populations (57.3%). Amazonas department had the highest rate of visits (2.36 per 10,000), while Nariño had the highest intensity of visits (1.94 visits per person). Caribbean region had the highest rate of visits (17.0 per 10,000 visits; 17.0-17.0), followed by the Amazon region (16.3 per 10,000 visits; 16.2-16.4). Conclusions: The annual visits burden of dermatomycosis in Colombia is high and concentrated in susceptible geographic areas, possibly due to socio-environmental factors. This health problem is overshadowed by chronic diseases and trauma but is often recurrent, and chronic, and induces out-of-pocket costs for treatment.

Mobilization of Endogenous CD34+/CD133+ Endothelial Progenitor Cells by Enhanced External Counter Pulsation for Treatment of Refractory Angina.

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (ß = -2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.

Endoscopic screening for identification of signet ring cell gastric cancer foci in carriers of germline pathogenic variants in CDH1.

To determine the preoperative detection of signet ring cancer cells (SRC) on upper endoscopy (EGD) in patients with CDH1 pathogenic variant (PV) undergoing gastrectomy. To evaluate the development of advanced diffuse gastric cancer (DGC) in patients choosing surveillance. Guidelines recommend prophylactic total gastrectomy (pTG) in CDH1 PV carriers with family history of DGC between 18 and 40 years. Annual EGD with biopsies according to established protocols is recommended in carriers with no SRC and no family history of DGC, with consideration of pTG. Retrospective analysis of asymptomatic patients with CDH1 PVs with ≥ 1 surveillance EGD. Outcomes included pre-operative EGD detection of SRC, surgical stage, and progression to advanced DGC in those electing surveillance with EGD. 48 patients with CDH1 PVs who had ≥ 1 EGD were included. 24/ 48 (50%) underwent gastrectomy, including pTG in 7 patients. SRCC were detected on gastrectomy specimen in 21/24 (87.5%). SRCs were identified by EGD in 17/21 patients who had SRCC on gastrectomy specimens (sensitivity 81%, 17/21). All cancers were stage pT1a. The remaining 17 patients (50% with a family history of gastric cancer) continue in annual EGD surveillance with a median follow-up of 34.6 months. No SRCC or advanced DGC have been diagnosed. No CDH1 PV carriers without SRCC on random biopsies followed in an endoscopic program developed advanced DGC over a median follow up of 3 years. In the short term, EGD surveillance might be a safe alternative to immediate pTG in experienced hands in referral centers.

Alzheimer disease-like neuropathologic changes in a geriatric baboon (Papio hamadryas).

IMPORTANCE: Alzheimer's disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, including the various genetic, environmental, and metabolic contributing factors. In an effort to better understand this complex disease, researchers have employed nonhuman primates as translational models. CASE PRESENTATION: This report aims to describe the AD-like neuropathology in the brain of a 37-year-old female baboon (Papio hamadryas), which at the time of her death made her the oldest hamadryas baboon at any member institution of the Association of Zoos and Aquariums. A diagnostic necropsy was performed, and the brain was evaluated for neurodegenerative disease. Frequent amyloid-ß deposits were identified, consistent with what has been described in other geriatric nonhuman primates. Phospho-tau pathology, including neurofibrillary tangles, a feature not well-described in other primate models, was also abundant. CONCLUSIONS AND RELEVANCE: Our results suggest that more detailed, prospective, longitudinal studies are warranted utilizing this particular species to see if they represent a viable model for human brain aging.