Lasting Impact of the COVID-19 Pandemic on Care and Prevention of Sexually Transmitted Infections in the Midwest.

BACKGROUND: The COVID-19 pandemic reduced the general accessibility of health services. Many sexually transmitted infection (STI) testing and treatment sites modified services (e.g., reduced hours, limited walk-in availability, decreased testing capacity), changes that may result in permanent change in STI service availability. At the same time, systems were driven to innovate in ways that could benefit patients. This study aimed to describe how the COVID-19 pandemic changed STI clinical services, with a focus on long-term impacts. METHODS: In July 2022, a phone survey was designed to assess services for STIs at the 105 STI testing and treatment providers in the St. Louis metropolitan statistical area. Sexually transmitted infection testing providers included STI clinics, primary care clinics that cater to a broad population, and community-based organizations, and excluded emergency departments and urgent care centers. In most cases, the survey was completed by a clinic manager, medical director, or nursing staff member. RESULTS: Of the 75 locations that were interviewed, 12 (16%) had not returned to prepandemic capacity and operations as of July 2022. Five sites had closed completely since the pandemic began, 3 of which are in the northwestern region of the metropolitan statistical area. Most (58.6%) of the open clinics had added telehealth appointments. CONCLUSIONS: Sexually transmitted infection testing sites decreased during the pandemic with lasting impact in one area of the Midwest. Resources to support STI infrastructure should be expanded. Maintaining updated information on STI care providers in the region can aid future assessments.

Angiolipoma of the Colon: A Rare Cause of Gastrointestinal Bleeding.

Angiolipomas are benign, subcutaneous tumors that are rarely found in the gastrointestinal tract. Still, because they may present with abdominal pain and rectal bleeding, it is important to recognize the clinical, radiological, and endoscopic findings associated with these masses. Herein we report a case of an angiolipoma of the colon diagnosed in a 49-year-old male presenting with self-limited gastrointestinal bleeding who subsequently underwent surgical resection without complications.

Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome.

Introduction: Fragile X Syndrome (FXS) is a monogenic condition that leads to intellectual disability along with behavioral and learning difficulties. Among behavioral and learning difficulties, cognitive flexibility impairments are among the most commonly reported in FXS, which significantly impacts daily living. Despite the extensive use of the Fmr1 knockout (KO) mouse to understand molecular, synaptic and behavioral alterations related to FXS, there has been limited development of translational paradigms to understand cognitive flexibility that can be employed in both animal models and individuals with FXS to facilitate treatment development. Methods: To begin addressing this limitation, a parallel set of studies were carried out that investigated probabilistic reversal learning along with other behavioral and cognitive tests in individuals with FXS and Fmr1 KO mice. Fifty-five adolescents and adults with FXS (67% male) and 34 age- and sex-matched typically developing controls (62% male) completed an initial probabilistic learning training task and a probabilistic reversal learning task. Results: In males with FXS, both initial probabilistic learning and reversal learning deficits were found. However, in females with FXS, we only observed reversal learning deficits. Reversal learning deficits related to more severe psychiatric features in females with FXS, whereas increased sensitivity to negative feedback (lose:shift errors) unexpectedly appear to be adaptive in males with FXS. Male Fmr1 KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female Fmr1 KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female Fmr1 KO mice were impaired in learning to choose a non-preferred spatial location to receive a food reward compared to that of WT mice. Neither male nor female Fmr1 KO mice exhibited a change in anxiety compared to that of WT mice. Discussion: Together, our findings demonstrate strikingly similar sex-dependent learning disturbances across individuals with FXS and Fmr1 KO mice. This suggests the promise of using analogous paradigms of cognitive flexibility across species that may speed treatment development to improve lives of individuals with FXS.

Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study.

BACKGROUND AND OBJECTIVES: Body mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder. METHODS: Participants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study). Age- and sex-specific BMI and height Z-scores were calculated using CDC 2000 references for participants younger than 18 years. For adults aged 18 years or older, height Z-scores were also calculated, and absolute BMI was reported. Univariate and multivariate linear regression analyses tested the associations between exposures, covariates, and BMI or height measured at the baseline visit. In children, the superimposition by translation and rotation analysis method was used to compare linear growth trajectories between FRDA and a healthy reference cohort, the Bone Mineral Density in Childhood Study (n = 1,535 used for analysis). RESULTS: Median age at the baseline was 20 years (IQR, 13-33 years); 49% (n = 475) were women. A substantial proportion of children (17%) were underweight (BMI-Z < fifth percentile), and female sex was associated with lower BMI-Z (ß = -0.34, p < 0.05). In adults, older age was associated with higher BMI (ß = 0.09, p < 0.05). Regarding height, in children, older age (ß -0.06, p < 0.05) and worse modified Friedreich Ataxia Rating Scale (mFARS) scores (ß = -1.05 for fourth quartile vs first quartile, p < 0.01) were associated with shorter stature. In girls, the magnitude of the pubertal growth spurt was less, and in boys, the pubertal growth spurt occurred later (p < 0.001 for both) than in a healthy reference cohort. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset (=0.09, p < 0.05) and longer guanine-adenine-adenine repeat length (shorter of the 2 GAA repeats, ß = -0.12, p < 0.01) were associated with shorter stature. Both adults and children with higher mFARS scores and/or who were nonambulatory were less likely to have height and weight measurements recorded at clinical visits. DISCUSSION: FRDA affects both weight gain and linear growth. These insights will inform assessments of affected individuals in both research and clinical settings.

Metabolism, HDACs, and HDAC Inhibitors: A Systems Biology Perspective.

Histone deacetylases (HDACs) are epigenetic enzymes that play a central role in gene regulation and are sensitive to the metabolic state of the cell. The cross talk between metabolism and histone acetylation impacts numerous biological processes including development and immune function. HDAC inhibitors are being explored for treating cancers, viral infections, inflammation, neurodegenerative diseases, and metabolic disorders. However, how HDAC inhibitors impact cellular metabolism and how metabolism influences their potency is unclear. Discussed herein are recent applications and future potential of systems biology methods such as high throughput drug screens, cancer cell line profiling, single cell sequencing, proteomics, metabolomics, and computational modeling to uncover the interplay between metabolism, HDACs, and HDAC inhibitors. The synthesis of new systems technologies can ultimately help identify epigenomic and metabolic biomarkers for patient stratification and the design of effective therapeutics.

Developmental dysplasia of the hip: can contrast-enhanced MRI predict the development of avascular necrosis following surgery?

OBJECTIVE: To investigate the performance of contrast-enhanced MRI for predicting avascular necrosis (AVN) of the treated femoral head after surgical reduction for developmental dysplasia of the hip (DDH) using qualitative and quantitative methods. METHODS AND MATERIALS: This IRB-approved, HIPAA compliant retrospective study included 47 children who underwent same-day contrast-enhanced MRI following unilateral surgical hip reduction between April 2009 and June 2018. Blinded to the clinical outcome, 3 reviewers (2 pediatric radiologists and 1 pediatric orthopedist) independently categorized the enhancement pattern of the treated femoral head. Signal intensities, measured using regions of interest (ROI), were compared between treated and untreated hips and percent enhancements were compared between hips that developed and did not develop AVN. Post-reduction radiographs were evaluated using Salter's criteria for AVN and Kalmachi and MacEwen's classification for growth disturbance. Non-parametric tests and Fisher exact test were used to compare enhancement values between AVN and non-AVN hips. Bonferroni correction was used for multiple comparisons. RESULTS: Ten (21%) out of the 47 children (7 boys and 40 girls; mean age 9.0 ± 4.7 months) developed AVN. Age at surgical reduction was significantly higher (p = 0.03) for hips that developed AVN. No significant differences were found in gender (p = 0.61), laterality (p = 0.46), surgical approach (p = 0.08), history of pre-operative bracing (p = 0.72), abduction angle (p = 0.18-0.44), enhancement pattern (p = 0.66-0.76), or percent enhancement (p = 0.41-0.88) between AVN and non-AVN groups. CONCLUSION: Neither enhancement pattern nor percent enhancement predicted AVN, suggesting that post-reduction conventional MRI does not accurately distinguish between reversible and permanent vascular injury.

Effect of Organic Food Intake on Nitrogen Stable Isotopes.

Food choices affect the isotopic composition of the body with each food item leaving its distinct isotopic imprint. The common view is that the natural abundance of the stable isotopes of nitrogen (expressed as δ15N) is higher in animals than in plants that constitute our contemporary diets. Higher δ15N is thus increasingly viewed as a biomarker for meat and fish intake. Here we show that organic compared to conventional farming increases plant δ15N to an extent that can appreciably impact the performance of δ15N as a biomarker. The error that can arise when organic plants are consumed was modelled for the entire range of proportions of plant versus animal protein intake, and accounting for various intakes of organic and conventionally grown crops. This mass balance model allows the interpretation of differences in δ15N in light of organic food consumption. Our approach shows that the relationship between δ15N and meat and fish intake is highly contextual and susceptible to variation at the population, community or group level. We recommend that fertilization practices and organic plant consumption must not be overlooked when using δ15N as a biomarker for meat and fish intake or to assess compliance to nutritional interventions.

Caregiver Decisional Conflict Before and After Consultation About Gastrostomy Tube Placement.

OBJECTIVES: Families describe decision-making about gastrostomy tube (g-tube) placement as challenging. We measured caregiver decisional conflict before and after initial g-tube consultation to evaluate the potential benefit of a decision aid and feasibility in testing it. METHODS: Families presenting for initial consultation about g-tube placement completed the decisional conflict scale (DCS) at 1 or 2 of 3 time points: before consultation, after consultation, and after viewing a video. The decision support consultation was a 2-hour structured meeting with a pediatric hospitalist, nurse practitioner, and dietitian that was focused on clarifying the indication, feasibility, safety, and family values around tube placement. The video described decision-making and lived experiences of families with tube feeding. RESULTS: We measured the decisional conflict of 61 caregivers. Preconsultation decisional conflict scores were high (mean = 38.7), but there was substantial variation between families (SD = 19.4). Baseline scores did not vary between clinically relevant subgroups. Postconsultation DCS scores were lower (17.9 and SD = 13.5 for consult alone; 12.7 and SD = 13.2 for consult with video). Three caregivers (7.7%) of families had residual decisional conflict scores >37.5, the threshold conventionally associated with decision delay. CONCLUSIONS: Measuring decisional conflict among caregivers deciding about pediatric g-tube is feasible during the clinical encounter. Residual decisional conflict after our institution's current decision support consultation model (with or without an additional video) was low, so development of an additional structured decision aid is not warranted. Further study of preconsult DCS variability across different clinical subgroups may help identify families benefiting from additional decisional support.

Dynamic effects of calcium on in vivo and ex vivo platelet behavior after trauma.

BACKGROUND: Mobilization of intra and extracellular calcium is required for platelet activation, aggregation, and degranulation. However, the importance of alterations in the calcium-platelet axis after injury is unknown. We hypothesized that in injured patients, in vivo initial calcium concentrations (pretransfusion) predict ex vivo platelet activation and aggregation, viscoelastic clot strength, and transfusion of blood products. We additionally hypothesized that increasing calcium concentrations ex vivo increases the expression of platelet activation surface receptors and platelet aggregation responses to agonist stimulation in healthy donor blood. METHODS: Blood samples were collected from 538 trauma patients on arrival to the emergency department. Standard assays (including calcium), platelet aggregometry (PA) and thromboelastometry (ROTEM) were performed. In PA, platelet activation (prestimulation impedance [Ω]) and aggregation responses to agonist stimulation (area under the aggregation curve [AUC]) with adenosine diphosphate (ADP), thrombin receptor-activating peptide, arachidonic acid (AA), and collagen (COL) were measured. Multivariable regression tested the associations of calcium with PA, ROTEM, and transfusions. To further examine the calcium-platelet axis, calcium was titrated in healthy blood. Platelet aggregometry and ROTEM were performed, and expression of platelet glycoprotein IIb/IIIa and P-selectin was measured by flow cytometry. RESULTS: The patients were moderately injured with normal calcium and platelet counts. Higher calcium on arrival (pretransfusion) was independently associated with increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP-stimulated, AUC; p = 0.002; thrombin receptor-activating peptide-stimulated, AUC; p = 0.038), and clot strength (ROTEM max clot firmness; p < 0.001), and inversely associated with 24-hour transfusions of blood, plasma, and platelets (all p < 0.005). Up-titrating calcium in healthy blood increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP, AA, COL-stimulated AUCs; p < 0.050), and expression of P-selectin (p = 0.003). CONCLUSION: Initial calcium concentrations (pretransfusion) are independently associated with platelet activation, aggregation, clot-strength, and transfusions after injury. These changes may be mediated by calcium driven expression of surface receptors necessary for platelet activation and aggregation. However, the therapeutic benefit of early, empiric calcium repletion in trauma patients remains undefined. LEVEL OF EVIDENCE: Prognostic, level V.

Osteochondral lesion of the talus in children: Are there MRI findings of instability?

PURPOSE: The purpose of our study was to investigate the performance of MRI findings to predict instability of osteochondral lesion of the talus (OLT) in children and the association between skeletal maturity and lesion stability. MATERIALS AND METHOD: This retrospective IRB-approved and HIPPA-compliant study included children with OLT, who underwent an ankle MRI examination between March 1, 2011, and May 31, 2018. Blinded to the clinical outcome, 2 radiologists retrospectively assessed each MRI study for the presence or absence of various features on the articular side, along the interface, and on the subchondral side of each lesion. Regional skeletal maturity was recorded. Lesion stability was classified using clinical and surgical findings. Mann-Whitney U, Chi-square, Fisher's exact, and Cochran-Armitage tests were used to compare demographic and MRI findings between children with stable and unstable lesions. RESULTS: Of the 48 ankles identified, 36 were stable (12.7 + 3.9 years) and 12 were unstable (14.2 + 1.6 years) lesions. None of the lesions presented as a detached fragment. Skeletal immaturity (p = 0.01) was significantly more common in stable than unstable lesions. No other MRI features were found to be significantly different between stable and unstable lesions, which included the presence of an effusion (p = 0.27), intra-articular body (p = 0.25), cartilage changes (p = 0.19), subchondral disruption (p = 0.51), T2-weighted signal intensity rim (p = 0.16), cysts (p = 0.48), marginal sclerosis (p = 0.70), and perilesional marrow edema (p = 0.17). CONCLUSION: Results from our study suggest that previously published OCD criteria using conventional MRI are not sufficient for predicting stability of OLT in children. Regional skeletal maturity and older age were more predictive of unstable lesions.

Retained Foreign Body Presenting as Pouch Stone After Continent Urinary Diversion.

Background: Continent urinary diversion is a procedure commonly performed in patients after cystectomy who wish to not have a urostomy. Well-documented complications after continent urinary diversion include urinary tract infections and formation of urinary stones. However, these are typically late complications, and few reports have described the onset of these urinary symptoms within 12 months of initial continent urinary diversion. Case Presentation: Herein we report a case of a 41-year-old woman with history of cystectomy with continent urinary diversion who presents with recurrent infections and a calculus in the pouch 10 months after the initial procedure. Upon surgical exploration for removal of the stone, it was discovered that the stone was in fact a calcified retained catheter tip. Conclusion: This case further highlights that stone formation within 12 months of a urinary diversion is unusual and should prompt additional work-up for foreign body.

Open-label pilot study of oral methylprednisolone for the treatment of patients with friedreich ataxia.

INTRODUCTION: In this study we assessed the effect of methylprednisolone on safety, tolerability, and ability in Friedreich ataxia (FRDA). METHODS: The study was an open-label trial of pulse methylprednisolone on 11 participants with FRDA. All participants followed a 28-day treatment cycle, repeated 7 times. Patients were assessed with the timed 25-foot walk (T25FW), 1-minute walk (1MW), the Friedreich Ataxia Rating Scale (FARS), and the 9-hole peg test (9HPT). Efficacy was tested by comparing baseline and week 26 visits, separated into adult and pediatric groups. RESULTS: In comparisons of participants' baseline and week 26 visits, only the pediatric cohort's 1MW score showed change (P < 0.05). The T25FW, the primary outcome measure, did not change significantly. DISCUSSION: Pediatric participants improved their gait distance in the 1MW, but did not significantly improve in other measures in this overall negative study. Methylprednisolone was generally well tolerated, suggesting that it may be useful for ambulatory children with FRDA if benefit is found with further study.

Giant cell lesion of the jaw as a presenting feature of Noonan syndrome.

This is a case of a 20-year-old woman who presented with a left jaw mass which was resected and found to be a giant cell granuloma of the mandible. Her history and physical examination were suggestive for Noonan syndrome which was confirmed with genetic testing and the finding of a PTPN11 gene mutation which has rarely been associated with giant cell lesions of the jaw. Given her particular genetic mutation and the presence of a giant cell lesion, we present a case of Noonan-like/multiple giant cell lesion syndrome.

Explicit and implicit attitudes towards people with intellectual disabilities: The role of contact and participant demographics.

BACKGROUND: Intellectual disability research has concentrated on self-reported explicit attitudes with little focus on implicit attitudes. Such attitudes are evaluations which occur with or without conscious awareness, respectively. This investigation examined participants' (N = 234) attitudes towards individuals with intellectual disabilities with reference to participants' gender, age, level of education, frequency of contact and closeness. METHOD: UK adults completed explicit (ATTID) and implicit attitude (ST-IAT) measures, and provided demographics via an online survey. RESULTS: Participant demographics predicted explicit attitudes-with differing cognitive, affective and behavioural associations. Contact frequency was most significant. Implicit attitudes were not predicted, evidencing implicit-explicit attitude differences. CONCLUSIONS: The results encourage more implicit-explicit attitude relationship research regarding disability. The associations between demographics, contact and implicit attitudes should be explored further. Research should question whether implicit attitudes reflect participants' true beliefs-denoting less importance to demographics-or whether they reflect wider societal values rather than individuals' attitudes.