Folate-Binding Protein Self-Aggregation Drives Agglomeration of Folic Acid Targeted Iron Oxide Nanoparticles.

Folate-conjugated nanomaterials have been widely investigated for drug and imaging-agent delivery. In this work, two folic acid (FA) conjugated iron oxide particles (IOP), a ∼40 nm diameter FA-IOP and a ∼450 nm diameter FA-IOP(FA-SeraMag), were synthesized. Both particles aggregated in the presence of serum folate-binding protein (FBP) at physiological concentration and buffer conditions. Mixing 0.01% w/w FA-conjugated iron oxide particles with FBP-induced agglomeration generated an average hydrodynamic particle diameter of 3800 ± 1100 nm for ∼40 nm FA-IOP and 4030 ± 1100 nm for FA-SeraMag as measured by dynamic light scattering (DLS). The presence of excess human serum albumin (HSA) (600 µM) did not prevent agglomeration of the ∼40 nm FA-IOP; however, it did inhibit agglomeration of FA-SeraMag. Atomic force microscopy measurement provided additional insight into particle morphology with the detection of individual particles in the agglomerate. This behavior is an example of a triggered cascade. A protein structural change is induced by FA binding, and the structural change favors aggregation of the ∼4 nm diameter FBPs on the particle surface; this further triggers the agglomeration of both the ∼40 and ∼450 nm diameter IOPs.

Immediate Versus Delayed Surgical Management of Infant Cryptorchidism With Inguinal Hernia.

INTRODUCTION: Cryptorchidism is commonly treated with orchiopexy at 6-12 months of age, often allowing time for undescended testicle(s) (UT) to descend spontaneously. However, when an inguinal hernia (IH) is also present, some surgeons perform orchiopexy and inguinal hernia repair (IHR) immediately rather than delaying surgery. We hypothesize that early surgical intervention provides no benefit for newborns with both IH and UT. METHODS: The Nationwide Readmissions Database was used to identify newborns with diagnoses of both IH and UT from 2010 to 2014. Patients were stratified by management: IHR performed on initial admission (Repair) or not (Deferral). Demographics, outcomes, and complications were compared. Results were weighted for national estimates. RESULTS: We analyzed 1306 newborns (64% premature) diagnosed with both IH and UT. IHR was performed at index admission in 30%. Repair was more common in premature babies (43% vs. 8% full-term, p < 0.001) and patients with congenital anomalies (33% vs. 27% without congenital anomaly, p = 0.012). There was no difference in readmission rates. Repair patients had higher rates of orchiectomy than did Deferral. No Deferral patients were readmitted for bowel resection, and <1% were readmitted for orchiectomy or hernia incarceration. CONCLUSION: In newborns with UT and IH, immediate repair is not associated with improved outcomes. Even with incarceration on initial presentation, rates of readmission with incarceration or bowel compromise for patients who undergo Deferral of surgery are minimal. Moreover, Repair newborns have higher rates of orchiectomy. We found no benefit to early operative intervention; thus, we recommend waiting until 6-12 months of age to reassess for surgery. LEVEL OF EVIDENCE: Level III TYPE OF STUDY: Retrospective Comparative Study.

Improper Restraint Use in Fatal Pediatric Motor Vehicle Collisions.

PURPOSE: Motor vehicle collisions (MVC) are the second leading cause of death in children and adolescents, but appropriate restraint use remains inadequate. Our previous work shows that about half of pediatric MVC victims presenting to our trauma center were unrestrained. This study evaluates restraint use among children and adolescents who did not survive after MVC. We hypothesize that restraint use is even lower in this population than in pediatric MVC patients who reached our trauma center. METHODS: We reviewed the local Medical Examiner's public records for fatal MVCs involving decedents <19 years old from 2010 to 2021. When restraint use was not documented, local Fire Rescue public records were cross-referenced. Patients were excluded if restraint use was still unknown. Age, demographics, and restraint use were compared using standard statistical methods. RESULTS: Of 199 reviewed cases, 92 met selection criteria. Improper restraint use was documented in 72 patients (78%). Most decedents were White (72% versus 28% Black) and male (74%), with a median age of 17 years [15-18]. Improper restraint use was more common among Black (92% vs 73% White, p = 0.040) and male occupants (85% vs 58% female, p = 0.006). Improper restraint use was lower in the Hispanic population (73%) compared to non-Hispanic individuals (89%), but this difference was not statistically significant (p = 0.090). CONCLUSION: Most pediatric patients who die from MVCs in our county are improperly restrained. While male and Black patients are especially high-risk, the overall dismal rates of restraint use in our pediatric population present an opportunity to improve injury prevention measures. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.

Role of wearable devices in cardiac telerehabilitation: A scoping review.

BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based comprehensive program that includes exercise training, health education, physical activity promotion, and extensive counseling for the management of cardiovascular risk factors. Wearable devices monitor certain physiological functions, providing biometric data such as heart rate, movement, sleep, ECG analysis, blood pressure, energy expenditure, and numerous other parameters. Recent evidence supports wearable devices as a likely relevant component in cardiovascular risk assessment and disease prevention. The purpose of this scoping review is to better understand the role of wearable devices in home-based CR (HBCR) and to characterize the evidence regarding the incorporation of wearable devices in HBCR programs and cardiovascular outcomes. METHODS & FINDINGS: We created a search strategy for multiple databases, including PubMed, Embase (Elsevier), CINAHL (Ebsco), Cochrane CENTRAL (Wiley), and Scopus (Elsevier). Studies were included if the patients were eligible for CR per Medicare guidelines and >18 years of age and if some type of wearable device was utilized during HBCR. Our search yielded 57 studies meeting all criteria. The studies were classified into 4 groups: patients with coronary heart disease (CHD) without heart failure (HF); patients with HF; patients with heart valve repair or replacement; and patients with exposure to center-based CR. In three groups, there was an upward trend toward improvement in quality of life (QOL) and peak VO2, less sedentary time, and an increase in daily step count in the intervention groups compared to control groups. CONCLUSIONS: HBCR using wearable devices can be a comparable alternative or adjunct to center-based CR for patients with CHD and HF. More studies are needed to draw conclusions about the comparability of HBCR to center-based CR in patients with heart valve repair or replacement.

United States county jail treatment and care of pregnant incarcerated persons with opioid use disorder.

BACKGROUND: Standards of care for pregnant persons with opioid use disorder (OUD) have been published across multiple institutions specializing in obstetrics and addiction medicine. Yet, this population faces serious barriers in accessing medications for OUD (MOUD) while incarcerated. Therefore, we examined the availability of MOUD in jails. METHODS: A Cross-sectional survey of jail administrators (n=371 across 42 states; 2018-2019) was conducted. Key indicators for this analysis include pregnancy testing at intake, number of county jails offering methadone or buprenorphine to pregnant incarcerated persons for detoxification on admission, continuation of pre-incarceration treatment, or linkage to post-incarceration treatment. Analyses were performed using SAS. FINDINGS: Pregnant incarcerated persons had greater access to MOUD than non-pregnant persons (χ2=142.10, p<0.0001). Larger jurisdiction size and urban jails were significantly more likely to offer MOUD (χ2=30.12, p<0.0001; χ2=26.46, p<0.0001). Methadone was the most common MOUD offered for continued care for all incarcerated persons. Of the 144 jails within a county with at least one public methadone clinic, 33% did not offer methadone treatment to pregnant persons, and over 80% did not provide linkage after release from jail. CONCLUSION: MOUD access was greater for pregnant incarcerated persons compared to non-pregnant persons. Compared to urban jails, rural jails were significantly less likely to offer MOUD, even as the number of opioid deaths in rural counties continues to surpass those in urban counties. The lack of post-incarceration linkage in counties with at least one public methadone clinic could be indicative of broader issues surrounding connections to MOUD resources.

An Anterior Cruciate Ligament Failure Mechanism.

BACKGROUND: Nearly three-quarters of anterior cruciate ligament (ACL) injuries occur as "noncontact" failures from routine athletic maneuvers. Recent in vitro studies revealed that repetitive strenuous submaximal knee loading known to especially strain the ACL can lead to its fatigue failure, often at the ACL femoral enthesis. HYPOTHESIS: ACL failure can be caused by accumulated tissue fatigue damage: specifically, chemical and structural evidence of this fatigue process will be found at the femoral enthesis of ACLs from tested cadaveric knees, as well as in ACL explants removed from patients undergoing ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: One knee from each of 7 pairs of adult cadaveric knees were repetitively loaded under 4 times-body weight simulated pivot landings known to strain the ACL submaximally while the contralateral, unloaded knee was used as a comparison. The chemical and structural changes associated with this repetitive loading were characterized at the ACL femoral enthesis at multiple hierarchical collagen levels by employing atomic force microscopy (AFM), AFM-infrared spectroscopy, molecular targeting with a fluorescently labeled collagen hybridizing peptide, and second harmonic imaging microscopy. Explants from ACL femoral entheses from the injured knee of 5 patients with noncontact ACL failure were also characterized via similar methods. RESULTS: AFM-infrared spectroscopy and collagen hybridizing peptide binding indicate that the characteristic molecular damage was an unraveling of the collagen molecular triple helix. AFM detected disruption of collagen fibrils in the forms of reduced topographical surface thickness and the induction of ~30- to 100-nm voids in the collagen fibril matrix for mechanically tested samples. Second harmonic imaging microscopy detected the induction of ~10- to 100-µm regions where the noncentrosymmetric structure of collagen had been disrupted. These mechanically induced changes, ranging from molecular to microscale disruption of normal collagen structure, represent a previously unreported aspect of tissue fatigue damage in noncontact ACL failure. Confirmatory evidence came from the explants of 5 patients undergoing ACL reconstruction, which exhibited the same pattern of molecular, nanoscale, and microscale structural damage detected in the mechanically tested cadaveric samples. CONCLUSION: The authors found evidence of accumulated damage to collagen fibrils and fibers at the ACL femoral enthesis at the time of surgery for noncontact ACL failure. This tissue damage was similar to that found in donor knees subjected in vitro to repetitive 4 times-body weight impulsive 3-dimensional loading known to cause a fatigue failure of the ACL. CLINICAL RELEVANCE: These findings suggest that some ACL injuries may be due to an exacerbation of preexisting hierarchical tissue damage from activities known to place larger-than-normal loads on the ACL. Too rapid an increase in these activities could cause ACL tissue damage to accumulate across length scales, thereby affecting ACL structural integrity before it has time to repair. Prevention necessitates an understanding of how ACL loading magnitude and frequency are anabolic, neutral, or catabolic to the ligament.