Greenhouse gas production from an intermittently dosed cold-climate wastewater treatment wetland.

This study explores the greenhouse gas (GHG) fluxes of nitrous oxide (N2O), methane (CH4) and carbon dioxide (CO2) from a two-stage, cold-climate vertical-flow treatment wetland (TW) treating ski area wastewater at 3 °C average water temperature. The system is designed like a modified Ludzack-Ettinger process with the first stage a partially saturated, denitrifying TW followed by an unsaturated nitrifying TW and recycle of nitrified effluent. An intermittent wastewater dosing scheme was established for both stages, with alternating carbon-rich wastewater and nitrate-rich recycle to the first stage. The system has demonstrated effective chemical oxygen demand (COD) and total inorganic nitrogen (TIN) removal in high-strength wastewater over seven years of winter operation. Following two closed-loop, intensive GHG winter sampling campaigns at the TW, the magnitude of N2O flux was 2.2 times higher for denitrification than nitrification. CH4 and N2O emissions were strongly correlated with hydraulic loading, whereas CO2 was correlated with surface temperature. GHG fluxes from each stage were related to both microbial activity and off-gassing of dissolved species during wastewater dosing, thus the time of sampling relative to dosing strongly influenced observed fluxes. These results suggest that estimates of GHG fluxes from TWs may be biased if mass transfer and mechanisms of wastewater application are not considered. Emission factors for N2O and CH4 were 0.27 % as kg-N2O-N/kg-TINremoved and 0.04 % kg-CH4-C/kg-CODremoved, respectively. The system had observed seasonal emissions of 600.5 kg CO2 equivalent of GHGs estimated over 130-days of operation. These results indicate a need for wastewater treatment processes to mitigate GHGs.

Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs).

BACKGROUND: Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline. METHODS: An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline. RESULTS: We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains. CONCLUSIONS: The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline. TRIAL REGISTRATION: EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.

Optimizing Temporal Summation of Heat Pain Using a Constant Contact Heat Stimulator.

Purpose: Temporal summation (TS) of pain occurs when pain increases over repeated presentations of identical noxious stimuli. TS paradigms can model central sensitization, a state of hyperexcitability in nociceptive pathways that promotes chronic pain onset and maintenance. Many experimenters use painful heat stimuli to measure TS (TS-heat); yet, TS-heat research faces unresolved challenges, including difficulty evoking summation in up to 30-50% of participants. Moreover, substantial variability exists between laboratories regarding the methods for evoking and calculating TS-heat. Patients and Methods: To address these limitations, this study sought to identify optimal parameters for evoking TS-heat in healthy participants with a commercially available constant contact heat stimulator, the Medoc TSA-II. Working within constraints of the TSA-II, stimulus trains with varying parameters (eg, stimulus frequency, baseline temp, peak temp, peak duration, testing site) were tested in a sample of 32 healthy, chronic pain-free participants to determine which combination best evoked TS-heat. To determine whether TS scoring method altered results, TS-heat was scored using three common methods. Results: Across all methods, only two trains successfully evoked group-level TS-heat. These trains shared the following parameters: site (palmar hand), baseline and peak temperatures (44°C and 50°C, respectively), and peak duration (0.5 s). Both produced summation that peaked at moderate pain (~50 out of 100 rating). Conclusion: Future TS-heat investigations using constant contact thermodes and fixed protocols may benefit from adopting stimulus parameters that include testing on the palmar hand, using 44°C baseline and 50°C peak temperatures, at ≥0.33 Hz stimulus frequency, and peak pulse durations of at least 0.5 seconds.

Tobramycin and Vancomycin in an In Vitro Model of Anterior Cruciate Ligament Allograft Decontamination.

BACKGROUND: Approximately 100,000 anterior cruciate ligament (ACL) reconstructions (ACLRs) occur annually in the United States, and postoperative surgical-site infection is a relatively rare but devastating complication, often leading to graft failure or septic arthritis of the knee, necessitating repeat surgery. Wrapping allografts in vancomycin-soaked gauze has been adopted as a common sterilization technique in the operating room to reduce surgical-site infection; however, identifying effective alternatives to vancomycin has not been extensively pursued. HYPOTHESIS: Tobramycin would be as effective as vancomycin in reducing the concentrations of Staphylococcus epidermidis bacteria on tendon allografts. STUDY DESIGN: Controlled laboratory study. METHODS: S. epidermidis strain ATCC 12228 was inoculated onto the human cadaveric gracilis tendon. The tendons were wrapped in sterile gauze saturated with tobramycin or vancomycin at various experimental concentrations. Bacteria remaining on the tendon were dislodged, serially diluted, and plated for colony counting. Statistical analysis was performed utilizing 2-way analysis of variance testing. Results were considered statistically significant when P < .05. RESULTS: Vancomycin (P = .0001) and tobramycin (P < .0001) reduced bacterial concentration. Tobramycin was found to produce a statistically significant reduction in bacterial concentration at concentrations as low as 0.1 mg/mL (P < .0001 and P = .01 at 10 and 20 minutes), while vancomycin produced a statistically significant reduction at a concentration as low as 2.5 mg/mL (P < .0001 at both 10 and 20 minutes). CONCLUSION: This study demonstrates that tobramycin is as effective as vancomycin in bacterial concentration reduction but can achieve this reduction level at lower doses. Further studies clarifying the biomechanical and cytotoxic effects of tobramycin on tendon tissue are indicated to solidify its use as a clinical alternative to vancomycin in ACLR. CLINICAL RELEVANCE: These results will begin establishing tobramycin as an alternative to vancomycin in ACL graft decontamination. Because of relatively frequent shortages of vancomycin, establishing tobramycin as an alternative agent is a useful option for the orthopaedic surgeon.

Opioid Receptor Mu 1 Gene (OPRM1) A118G Polymorphism and Emotional Modulation of Pain.

Purpose: The A118G polymorphism in the opioid receptor mu 1 gene (OPRM1) is associated with decreased opioid receptor availability, altered emotion, and increased pain. Given that emotions modulate pain (positive emotions inhibit pain, negative emotions enhance pain), we predicted that G allele carriers would experience impaired emotional modulation of pain compared to non-G allele carriers. Patients and Methods: Emotional pictures (ie, erotica, neutral, attack) from the International Affective Picture System were used by permission from the authors to experimentally manipulate emotions in 64 adult participants while painful electrocutaneous stimulations were delivered in a cross-sectional study. Ratings of arousal and valence/pleasure were made in response to pictures, and pain ratings and a physiological measure of spinal nociception (ie, nociceptive flexion reflex, NFR) were collected in response to painful stimulations. Secondary analyses were conducted to examine the relationship between the A118G polymorphism and emotional modulation of pain/NFR. Results: Exposure to emotional pictures elicited similar changes in valence, but G-carriers rated erotic pictures as more arousing. In non-carriers, pain was facilitated by attack pictures and pain and NFR were inhibited by erotic pictures relative to neutral pictures. Among G-carriers, pain was facilitated by negative emotional pictures but there was no pain or NFR inhibition by positive emotional pictures. Conclusion: The altered response to pleasant stimuli further supports the role of opioids in appetitive behavior and describes how the A118G polymorphism may prevent carriers from inhibiting pain during pleasure.

Carbon monoxide poisoning: A problem uniquely suited to a medicinal inorganic chemistry solution.

Carbon monoxide poisoning is one of the most common forms of poisoning in the world. Although the primary mode of treatment, oxygen therapy, is highly effective in many cases, there are instances in which it is inadequate or inappropriate. Whereas oxygen therapy relies on high levels of a low-affinity ligand (O2) to displace a high-affinity ligand (CO) from metalloproteins, an antidote strategy relies on introducing a molecule with a higher affinity for CO than native proteins (Kantidote,CO > Kprotein,CO). Based on the fundamental chemistry of CO, such an antidote is most likely required to be an inorganic compound featuring an electron-rich transition metal. A review is provided of the protein-, supramolecular complex-, and small molecule-based CO poisoning antidote platforms that are currently under investigation.

Driver behavior while using Level 2 vehicle automation: a hybrid naturalistic study.

Vehicle automation is becoming more prevalent. Understanding how drivers use this technology and its safety implications is crucial. In a 6-8 week naturalistic study, we leveraged a hybrid naturalistic driving research design to evaluate driver behavior with Level 2 vehicle automation, incorporating unique naturalistic and experimental control conditions. Our investigation covered four main areas: automation usage, system warnings, driving demand, and driver arousal, as well as secondary task engagement. While on the interstate, drivers were advised to engage Level 2 automation whenever they deemed it safe, and they complied by using it over 70% of the time. Interestingly, the frequency of system warnings increased with prolonged use, suggesting an evolving relationship between drivers and the automation features. Our data also revealed that drivers were discerning in their use of automation, opting for manual control under high driving demand conditions. Contrary to common safety concerns, our data indicated no significant rise in driver fatigue or fidgeting when using automation, compared to a control condition. Additionally, observed patterns of engagement in secondary tasks like radio listening and text messaging challenge existing assumptions about automation leading to dangerous driver distraction. Overall, our findings provide new insights into the conditions under which drivers opt to use automation and reveal a nuanced behavioral profile that emerges when automation is in use.

A point-prevalence study of body mass indices in HIV-positive and HIV-negative patients admitted to hospital with COVID-19 in South Africa.

Background: Obesity is now well recognised as a risk factor for severe COVID-19, but the true prevalence of obesity in hospitalised adults with COVID-19 remains unclear because formal body mass indices (BMIs) are not routinely measured on admission. Objectives: To describe the true prevalence of obesity measured by the BMI, and associated comorbidities, in patients hospitalised with severe COVID-19, including people with HIV (PWH). Methods: We conducted a point-prevalence study of measured BMI in consecutive patients with severe COVID-19 admitted to the medical COVID-19 wards in a tertiary academic hospital in Cape Town, South Africa (SA). Patients were enrolled over a 2-week period during the peak of the first COVID-19 wave in SA. Results: We were able to measure the BMI in 122 of the 146 patients admitted during the study period. The prevalence of HIV was 20% (n=24/122). Most of the participants were overweight or obese (n=104; 85%), and 84 (68.9%) met criteria for obesity. The mean (standard deviation) BMI was 33 (7.5), and 34.5 (9.1) in PWH. Of PWH, 83% (n=20/24) were overweight or obese and 75% (n=18) met criteria for obesity. Multimorbidity was present in 22 (92%) of PWH. Conclusion: We found that most patients, including PWH, met criteria for being overweight or obese. The high prevalence of obesity in PWH and severe COVID-19 reinforces the need for targeted management of non-communicable diseases, including obesity, in PWH. Study synopsis: What the study adds. We found that the true prevalence of obesity, including in people with HIV (PWH), measured with the formal body mass index in hospitalised patients with severe COVID-19 was much higher than reported previously.Multimorbidity was present in over half of all patients, and in 92% of PWH. Implications of the findings. Urgent public health measures are required to tackle the rise in obesity, including in low- and middle-income countries.HIV care must integrate management of non-communicable diseases, including obesity.The pathogenic mechanism of the link between obesity and severe COVID-19 needs further research.

Anterolateral Radial Meniscus Tear Repair using Traction Suture and Super-Hashtag Technique.

Radial meniscus tears occur commonly as traumatic tears in younger patients, as well as in association with concomitant degenerative changes. Traditional management of these tears has centered around partial meniscectomy; however, there has been a more recent trend toward preserving the meniscus and attempting repair. Because of the gapping and displacement that frequently occurs with these tears, repair is often challenging and is done under high amounts of tension. The following article describes a technique using a traction suture to aid in maintaining reduction throughout repair. This is followed by the use of a combination of techniques to form a "super-hashtag" configuration of both vertical and horizontal mattress sutures, leading to a secure repair under little tension.

Horizontal Cleavage Tear Meniscal Repair Using All-Inside Circumferential Compression Sutures.

Horizontal cleavage meniscus tears occur more frequently in older patient populations with degenerative changes within the meniscus. Traditionally, they have been managed with nonsurgical interventions or with partial meniscectomy. As increasing evidence demonstrates the link between partial meniscectomy and progressive osteoarthritis with these types of tears, as well as worse long-term outcomes and reduced cost savings, surgical repair of horizontal cleavage meniscal tears has increased in appropriate patients. This technique article highlights the evaluation, indications, and preferred repair technique for horizontal cleavage tears in appropriately selected patients.

Assessing knowledge and confidence of surgical residents in inguinal hernia repair using a low-cost synthetic model.

PURPOSE: Open repair of groin hernia is an essential skill for the general surgeon. This study aimed to develop a low-cost hernia model based on a validated high-fidelity model and assess its effectiveness in teaching inguinal hernia repair to surgical trainees from many institutions throughout Africa. METHODS: Using inexpensive, locally available materials, a low-cost hernia model was created. Six models were constructed, and a workshop was conducted for surgical residents. Pre- and post-workshop surveys were administered to assess knowledge, confidence, and understanding. Statistical analyses were performed using paired t tests and the Wilcoxon signed-rank test. RESULTS: The low-cost hernia model consisted of various readily available materials and cost an average of $5.07. Sixty-eight trainees participated in the workshop, and 59 completed the post-workshop survey. Participants reported a significant increase in confidence for both mesh and non-mesh repairs and an improved understanding of hernia anatomy after the workshop. Trainees scored an average of 5.6 (SD 1.9) out of 10 questions on the pre-workshop quiz and 7.9 (SD 1.4) out of 10 on the post-workshop quiz (p < 0.001), indicating improved knowledge. All trainees supported the use of the model for education. CONCLUSION: The low-cost hernia model demonstrated its effectiveness in enhancing trainees' understanding of hernia anatomy and increasing their confidence in hernia repair. Integrating low-cost hernia models into training programs can help improve trainees' knowledge and confidence in a safe and affordable environment.

Review: Discogenic Back Pain: Update on Treatment.

Purpose of Review: Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography. Recent Findings: Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on data derived from treatment of chronic LBP (CLBP). Summary: Despite the scarcity of data for the treatment of DBP, treatments do exist with varying efficacy for DBP. Novel techniques such as the use of biologics may provide another avenue for treatment though further studies are needed to better evaluate the most efficacious regimen for both novel and existing treatments.

Posterior Meniscal Root Repair With Transtibial Double Tunnel Pullout Technique and Anchor Fixation.

Meniscus root tears are tears that occur within 1 cm of the meniscus root attachment to the tibia. If not repaired, root tears will lead to altered knee biomechanics and accelerated degenerative changes in the knee. In this surgical technique, we demonstrate repair of a meniscus root tear with an all-inside suture repair of the posterior meniscus that is then passed through 2 transtibial tunnels and then fixed with an anchor. After surgery, patients are non-weightbearing for 4 weeks and can return to activity by 6 months.

Heritable induced resistance in Arabidopsis thaliana: Tips and tools to improve effect size and reproducibility.

Over a decade ago, three independent studies reported that pathogen- and herbivore-exposed Arabidopsis thaliana produces primed progeny with increased resistance. Since then, heritable induced resistance (h-IR) has been reported across numerous plant-biotic interactions, revealing a regulatory function of DNA (de)methylation dynamics. However, the identity of the epi-alleles controlling h-IR and the mechanisms by which they prime defense genes remain unknown, while the evolutionary significance of the response requires confirmation. Progress has been hampered by the relatively high variability, low effect size, and sometimes poor reproducibility of h-IR, as is exemplified by a recent study that failed to reproduce h-IR in A. thaliana by Pseudomonas syringae pv. tomato (Pst). This study aimed to improve h-IR effect size and reproducibility in the A. thaliana-Pst interaction. We show that recurrent Pst inoculations of seedlings result in stronger h-IR than repeated inoculations of older plants and that disease-related growth repression in the parents is a reliable marker for h-IR effect size in F1 progeny. Furthermore, RT-qPCR-based expression profiling of genes controlling DNA methylation maintenance revealed that the elicitation of strong h-IR upon seedling inoculations is marked by reduced expression of the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1) gene, which is maintained in the apical meristem and transmitted to F1 progeny. Two additional genes, MET1 and CHROMOMETHYLASE3 (CMT3), displayed similar transcriptional repression in progeny from seedling-inoculated plants. Thus, reduced expression of DDM1, MET1, and CMT3 can serve as a marker of robust h-IR in F1 progeny. Our report offers valuable information and markers to improve the effect size and reproducibility of h-IR in the A. thaliana-Pst model interaction.

Plasma lipopolysaccharide elevations in cattle associated with early-stage infection by Fasciola hepatica.

Fasciolosis is an endemic zoonotic parasitic disease with significant impacts on human health and both animal health and production. Early post-infection impacts on the host remain unclear. The objective of this study was to determine the changes, if any, to levels of endotoxin in cattle plasma in response to early-stage infection with Fasciola hepatica. Thirty-six (36) commercial bred cattle were experimentally infected with approximately 400 viable metacercariae. Plasma lipopolysaccharide (endotoxin) levels were examined on 24 occasions from 0 h before infection to 336 h after infection using the Limulus Amoebocyte Lysate chromogenic end point assay and compared with that of six (6) uninfected control animals. Peak lipopolysaccharide levels in infected animals were reached at 52 h after infection and returned to pre-infection levels at time 144 h after infection. Infected animals had significantly elevated lipopolysaccharide levels between 24 and 120 h after infection when compared to uninfected animals. The mean change in endotoxin units (EU)/mL over time after infection was statistically significant in infected animals. Elevations of lipopolysaccharide occurred in all infected animals suggesting a possible repeatable and titratable endotoxemia conducive to therapeutic agent model development.

More Is Not Merrier: Increasing Numbers of All-Inside Implants Do Not Correlate with Higher Odds of Revision Surgery.

The purpose of this study was to evaluate the relationship between the number of all-inside meniscal repair implants placed and the risk of repair failure. We hypothesized that the use of higher numbers of all-inside meniscus repair implants would be associated with increased failure risk. A retrospective chart review identified 351 patients who underwent all-inside meniscus repair between 2006 and 2013 by a sports medicine fellowship-trained orthopaedic surgeon at a single institution. Patient demographics (age, body mass index [BMI], sex) and surgical data (number of implants used, concomitant anterior cruciate ligament reconstruction [cACLR], and tear type/size/location) were recorded. Patients who received repairs in both menisci or who had follow-up < 1-year postoperatively were excluded. Repair failure was identified through chart review or patient interviews defined as a revision surgery on the index knee such as partial meniscectomy, total knee arthroplasty, meniscus transplant, or repeat repair. Logistic regression modeling was utilized to evaluate the relationship between the number of implants used and repair failure. A total of 227 all-inside meniscus repairs were included with a mean follow-up of 5.0 ± 3.0 years following surgery. Repair failure was noted in 68 knees (30.3%)-in 28.1% of knees with fewer than four implants and in 35.8% of knees with four or more implants (p = 0.31). No significant increase in failure was observed with increasing number of all-inside medial (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.79-1.7; p = 0.46) or lateral (OR: 0.86; 95% CI: 0.47-1.57; p = 0.63) implants after controlling for patient age, BMI, cACLR, tear type, or size. Tears of the lateral meniscus located in the red-white and white-white zones had lower odds of failure (OR: 0.14; 95% CI: 0.02-0.88; p = 0.036) than tears within the red-red zone, and patients with cACLR had lower odds of repair failure (OR: 0.40; 95% CI: 0.18-0.86, p = 0.024) than those without. The number of all-inside implants placed during meniscus tear repair did not affect the likelihood of repair failure leading to reoperation after controlling for BMI, age, tear type, size, location, and cACLR. LEVEL OF EVIDENCE: III.

Does the Use of Probe-based Near-infrared Autofluorescence Parathyroid Detection Benefit Parathyroidectomy?: A Randomized Single-center Clinical Trial.

OBJECTIVE: To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy. BACKGROUND: Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit. RESULTS: One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient ( P <0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient ( P =0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient ( P <0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P =0.005). CONCLUSION: Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.

Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.

Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure (IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in TTC28, KIAA1731, ADAMTS5, OR2W3, OR10A6, SAXO2, KCTD18, CHCHD6, and UPK1A were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (PDC80). While missense mutations in TINAG, CHCHD6, GSTZ1, and SEMA4G were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (MPR80). The same coding SNP in CHCHD6 which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (p = 5.54 × 10-6) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have protective associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.

Identifying Parathyroids in Pediatric Thyroid/Parathyroid Surgery by Near Infrared Autofluorescence.

OBJECTIVES: Compared to adult patients undergoing thyroid surgery, pediatric patients have higher rates of hypoparathyroidism often related to parathyroid gland (PG) inadvertent injury or devascularization. Previous studies have shown that near-infrared-autofluorescence (NIRAF) can be reliably used intraoperatively for label-free parathyroid identification, but all prior studies have been performed in adult patients. In this study, we assess the utility and accuracy of NIRAF with a fiber-optic probe-based system to identify PGs in pediatric patients undergoing thyroidectomy or parathyroidectomy. METHODS: All pediatric patients (under 18 years of age) undergoing thyroidectomy or parathyroidectomy were enrolled in this IRB-approved study. The surgeon's visual assessment of tissues was first noted and the surgeon's confidence level in the tissue identified was recorded. A fiber-optic probe was then used to illuminate tissues-of-interest with a wavelength of 785 nm and resulting NIRAF intensities from these tissues were measured while the surgeon was blinded to results. RESULTS: NIRAF intensities were measured intraoperatively in 19 pediatric patients. Normalized NIRAF intensities for PGs (3.63 ± 2.47) were significantly higher than that of thyroid (0.99 ± 0.36, p < 0.001) and other surrounding soft tissues (0.86 ± 0.40, p < 0.001). Based on the PG identification ratio threshold of 1.2, NIRAF yielded a detection rate of 95.8% (46/48 pediatric PGs). CONCLUSION: Our findings indicate that NIRAF detection can potentially be a valuable and non-invasive technique to identify PGs during neck operations in the pediatric population. To our knowledge, this is the first study in children to assess the accuracy of probe-based NIRAF detection for intraoperative parathyroid identification. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 133:3208-3215, 2023.

Risk Factors for Early Conversion Total Hip Arthroplasty After Pipkin IV Femoral Head Fracture.

OBJECTIVES: To determine risk factors for early conversion total hip arthroplasty (THA) in Pipkin IV femoral head fractures. DESIGN: Retrospective cohort. SETTING: Two level I trauma centers. PATIENTS AND INTERVENTION: One hundred thirty-seven patients with Pipkin IV fractures meeting inclusion criteria with 1 year minimum follow-up managed from 2009 to 2019. MAIN OUTCOME MEASUREMENT: Patients were separated into groups by the Orthopaedic Trauma Association/AO Foundation (OTA/AO) classification of femoral head fracture: 31C1 (split-type fractures) and 31C2 (depression-type fractures). Multivariable regression was performed after univariate analysis comparing patients requiring conversion THA with those who did not. RESULTS: We identified 65 split-type fractures, 19 (29%) underwent conversion THA within 1 year. Surgical site infection ( P = 0.002), postoperative hip dislocation ( P < 0.0001), and older age ( P = 0.049) resulted in increased rates of conversion THA. However, multivariable analysis did not identify independent risk factors for conversion. There were 72 depression-type fractures, 20 (27.8%) underwent conversion THA within 1 year. Independent risk factors were increased age ( P = 0.01) and posterior femoral head fracture location ( P < 0.01), while infrafoveal femoral head fracture location ( P = 0.03) was protective against conversion THA. CONCLUSION: Pipkin IV fractures managed operatively have high overall risk of conversion THA within 1 year (28.5%). Risk factors for conversion THA vary according to fracture subtype. Hip joint survival of fractures subclassified OTA/AO 31C1 likely depends on patient age and postoperative outcomes such as surgical site infection and redislocation. Pipkin IV fractures subclassified to OTA/AO 31C2 type with suprafoveal and posterior head impaction and older age should be counseled of high conversion risk with consideration for alternative management options. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.