Impact of moral injury and posttraumatic stress disorder on health care utilization and suicidality in rural and urban veterans.

This study explored the impact of moral injury (MI) and posttraumatic stress disorder (PTSD) on health care utilization, mental health complexity, and suicidality in rural and urban veterans. Analyses combined data from the Salt Lake City PTSD Clinic Intake Database and the Department of Veterans Affairs Corporate Data Warehouse. Participants (N = 1,545; Mage = 45.9 years) were predominately male (88.3%) and White (87.8%). Adjusted analyses indicated associations between a 1-unit increase in Moral Injury Events Scale (MIES) score and increased mental health complexity, RR = 1.01, 95% CI [1.01, 1.02], p < .001; psychotropic medication utilization, RR = 1.01, 95% CI [1.01, 1.03], p < .001; VA drug class count, RR = 1.01, 95% CI [1.00, 1.01], p = .030; outpatient utilization, RR = 1.01, 95% CI [1.01, 1.02], p < .001; and mental health outpatient utilization, RR = 1.01, 95% CI [1.00, 1.03], p < .001. For the MIES x PTSD interaction, all associations remained statistically significant with similar estimated effects. However, for rural veterans, this interaction did not significantly affect utilization. Among those with PTSD, a 1-unit MIES increase was associated with an increased risk of suicidality, OR = 1.02, 95% CI [1.01, 1.04], and psychiatric admission, OR = 1.02, 95% CI [1.00, 1.04]. Findings suggest that higher MIES scores predict increased health care utilization and mental health complexity. Further, PTSD combined with higher MIES scores may increase the risk of suicidality and psychiatric admission. Rural veterans with PTSD and higher MIES scores may require additional outreach and intervention.

Itching to find a diagnosis.

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Academy IRIS® Registry Analysis of Incidence of Laser Capsulotomy Due to Posterior Capsule Opacification After Intraocular Lens Implantation.

Purpose: Academy IRIS® (Intelligent Research in Sight) Registry was used to determine the incidence of postoperative neodymium-doped yttrium aluminum garnet laser capsulotomy (Nd:YAG) and time to posterior capsular opacification (PCO) diagnosis based on intraocular lens (IOL) type and brand. Methods: This retrospective analysis included eyes implanted with 1 of 2 IOL brands, with ≥365 days of follow-up available in the IRIS Registry, and ≥2 visits within 180 days of surgery. Analyses included Nd:YAG incidence due to PCO within 1 year after surgery by IOL type and brand, mean time to PCO diagnosis, and mean time to Nd:YAG. Results: Of 89,947 eyes after cataract surgery, 24,834 (28%) had PCO diagnosis within 365 days, and 9262 (10%) underwent Nd:YAG; 4.1% of 57,523 eyes with monofocal and 21.2% of 32,424 eyes with diffractive multifocal (MF) or diffractive extended depth of focus (EDOF) IOLs had Nd:YAG. Nd:YAG was 3.2 times more likely in eyes with diffractive MF or diffractive EDOF IOLs versus monofocal. For monofocal IOLs, 3.2% of eyes with AcrySof® and 8.1% of eyes with Tecnis® had Nd:YAG (P<0.0001). For diffractive MF or diffractive EDOF IOLs, 13.0% of eyes with AcrySof and 21.7% of eyes with Tecnis had Nd:YAG (P<0.0001). Nd:YAG risk was 2.4 times higher in eyes with Tecnis versus AcrySof IOLs. Overall, mean time to PCO diagnosis and Nd:YAG was 150.7 and 180.7 days. Mean time to PCO for monofocal versus diffractive MF or diffractive EDOF IOLs was 165.3 versus 139.7 days (P<0.0001). Mean time to Nd:YAG for monofocal versus diffractive MF or diffractive EDOF IOLs was 196.4 versus 175.3 days (P<0.05). Conclusion: Real-world data for AcrySof and Tecnis IOLs revealed lower Nd:YAG rates and longer time to PCO diagnosis and Nd:YAG after monofocal versus diffractive multifocal or diffractive EDOF implantation. Nd:YAG rates were significantly lower with AcrySof versus Tecnis IOLs.

Utility of Cardiac Magnetic Resonance Imaging in Predicting Atrial Arrhythmias in Repaired Tetralogy of Fallot.

Arrhythmias are the leading cause of morbidity and mortality in repaired tetralogy of Fallot (TOF), and over 20% of these patients will develop a sustained atrial arrhythmia during their lifetimes. Cardiac magnetic resonance imaging (cMRI) is frequently performed in TOF, although its ability to identify patients at risk of atrial arrhythmias is uncertain. Adult TOF patients (n = 175) with no history of atrial arrhythmia who underwent cMRI between 2003 and 2020 at a single tertiary care center were identified. Clinical characteristics and imaging findings were evaluated to identify a predilection for atrial arrhythmias using Kaplan-Meier survival analysis and log-rank testing. Multivariable Cox regression was used to determine independent predictors of atrial arrhythmias. Over a median follow-up of 3.6 years, 29 patients (17%) developed atrial arrhythmias. Independent predictors of atrial arrhythmia included age (hazard ratio [HR] 1.06 per 1-year increase, 95% confidence interval [CI] 1.02 to 1.09, p = 0.002), diabetes mellitus (HR 4.26, 95% CI 1.26 to 14.41, p = 0.020), indexed right ventricular end-diastolic volume (RVEDVi), (HR 1.20 per 10-ml/m2 increase, 95% CI 1.05 to 1.39, p = 0.010), and moderate or greater tricuspid regurgitation (TR) (HR 6.32, 95% CI 2.15 to 18.60, p = 0.001). Utilizing Kaplan-Meier analysis, patients with at least mild right ventricular dilation (RVEDVi >100 ml/m2, p = 0.047) and greater than or equal to moderate TR (p <0.001) were found to be significantly more likely to develop atrial arrhythmias. In conclusion, cMRI can help to identify TOF patients at increased risk for atrial arrhythmia beyond standard clinical and imaging data by better quantifying RVEDVi and degree of TR.

A scoping review of veteran suicide prevention programs in Native American communities and in the general population.

Suicide is a major public health problem that disproportionately impacts veterans in the general U.S. population. Recent analyses indicate that American Indian and Alaska Native (AI/AN) veterans may be two to three times as likely as non-Hispanic White veterans to experience suicidal ideation. Although suicide prevention programs have been successfully implemented for many at-risk populations, to our knowledge, none have been designed or implemented for AI/AN veterans. To address this gap, we conducted a scoping review of suicide prevention programs with the objective of identifying promising strategies and lessons learned to identify promising practices for preventing suicide among AI/AN veterans. We conducted two parallel literature searches-a review of suicide prevention programs for the general U.S. adult population and AI/AN communities. We rated programs on 16 criteria, covering five domains-best practices in suicide prevention, U.S. Department of Veterans Affairs (VA) Office of Rural Health Promising Practice criteria, cultural fit, care coordination, and outcomes. Our findings indicate that many of the VA evidence-based or best practice programs are available system-wide, but none have been tailored for AI/AN veterans or the communities in which they live. Conversely, we found that many culturally specific programs implemented in AI/AN communities were rarely disseminated beyond tribal land and none were specifically developed for veterans. Based upon these findings, and to advance suicide prevention programs for AI/AN veterans, we propose a suicide prevention model that builds upon existing VA infrastructure to disseminate best practices to AI/AN communities and integrate tribal-specific cultural approaches to suicide prevention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Burden and Impact of Arrhythmias in Repaired Tetralogy of Fallot.

PURPOSE OF REVIEW: Arrhythmias are a leading cause of morbidity and mortality following repair of tetralogy of Fallot (TOF). This review will highlight current understanding of arrhythmia pathogenesis in this patient population and review novel therapeutic options. RECENT FINDINGS: Risk factors for developing ventricular arrhythmias in repaired TOF have thus far been better defined than for atrial arrhythmias. Growing understanding of the pathophysiology of arrhythmias, development of risk stratification models, and novel techniques such as electrophysiologic ultrahigh-density mapping should help to better identify patients that benefit from advanced therapies such as ablation and implantable cardioverter defibrillators. Atrial and ventricular arrhythmias are common in TOF patients. Methods of risk stratification and therapeutic approaches are rapidly evolving, leading to ever improving clinical outcomes in this patient population.

"We Got an Invite into the Fortress": VA-Community Partnerships for Meeting Veterans' Healthcare Needs.

Responding to identified needs for increased veterans' access to healthcare, in 2010 the United States Department of Veterans Affairs (VA) launched the Veteran Community Partnership (VCP) initiative to "foster seamless access to, and transitions among, the full continuum of non-institutional extended care and support services in VA and the community". This initiative represents an important effort by VA to promote collaboration with a broad range of community organizations as equal partners in the service of veteran needs. The purpose of the study is an initial assessment of the VCP program. Focus group interviews conducted in six sites in 2015 included 53 representatives of the local VA and community organizations involved with rural and urban VCPs across the US. Interview topics included the experiences and practices of VCP members, perceived benefits and challenges, and the characteristics and dynamics of rural and urban areas served by VCPs. Using a community-oriented conceptual framework, the analyses address VCP processes and preliminary outcomes, including VCP goals and activities, and VCP members' perceptions of their efforts, benefits, challenges, and achievements. The results indicate largely positive perceptions of the VCP initiative and its early outcomes by both community and VA participants. Benefits and challenges vary by rural-urban community context and include resource limitations and the potential for VA dominance of other VCP partners. Although all VCPs identified significant benefits and challenges, time and resource constraints and local organizational dynamics varied by rural and urban context. Significant investments in VCPs will be required to increase their impacts.

Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.

ALX4 is a homeobox gene expressed in the mesenchyme of developing bone and is known to play an important role in the regulation of osteogenesis. Enlarged parietal foramina (EPF) is a phenotype of delayed intramembranous ossification of calvarial bones due to variants of ALX4. The contrasting phenotype of premature ossification of sutures is observed with heterozygous loss-of-function variants of TWIST1, which is an important regulator of osteoblast differentiation. Here, we describe an individual with a large cranium defect, with dominant transmission from the mother, both carrying disease causing heterozygous variants in ALX4 and TWIST1. The distinct phenotype of absent superior and posterior calvarium in the child and his mother was in sharp contrast to the other affected maternal relatives with a recognizable ALX4-related EPF phenotype. This report demonstrates comorbid disorders of Saethre-Chotzen syndrome and EPF in a mother and her child, resulting in severe skull defects reminiscent of calvarial abnormalities observed with bilallelic ALX4 variants. To our knowledge this is the first instance of ALX4 and TWIST1 variants acting synergistically to cause a unique phenotype influencing skull ossification.

Effects of orally administered gabapentin, tramadol, and meloxicam on ocular variables in healthy dogs.

OBJECTIVE: To determine the effects of gabapentin, tramadol, and meloxicam on tear production, intraocular pressure (IOP), pupillary diameter, tear break-up time, and corneal touch threshold in healthy dogs when given orally for 3 days. ANIMALS: 9 healthy research Beagles. PROCEDURES: A randomized, blinded, case-crossover study with a 6-sequence, 3-treatment, and 3-period design was performed. A 7-day acclimation period was followed by 3 treatment phases, each with a 3-day treatment period followed by a 7-day washout period for 3 different drugs. Block randomization was used to group dogs for treatments with drug A (gabapentin), B (tramadol), or C (meloxicam). Measurements of tear production, IOP, pupillary diameter, tear break-up time, and corneal touch threshold were performed on a schedule. A generalized mixed-effects linear regression model was created for each ocular variable, accounting for repeated measures within individuals. RESULTS: Intraocular pressure was the only variable to have differed substantially between the first 5 and last 2 days of the acclimation period. When treatment phase, day, time of day, dog identification, baseline value, and eye were accounted for, the mean IOP was lower for dogs during treatment phases with gabapentin or tramadol, compared with meloxicam, but this difference was not considered clinically meaningful. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that a minimum 5-day acclimation period is necessary for IOP measurements to return to baseline in dogs. The statistically identified effect of gabapentin and tramadol on IOP in dogs of the present study warrants further investigation. It is possible that at higher dosages, or in dogs with glaucoma, this effect may become clinically significant.

Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced skin pigmentation.

Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Rα. Taken together, NRF2 and IL-6Rα signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target.

Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections.

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections.

Clonal Vγ6+Vδ4+ T cells promote IL-17-mediated immunity against Staphylococcus aureus skin infection.

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1ß, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4 However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

Theranostic biocomposite scaffold membrane.

Acute and chronic wounds affect millions and are associated with billions of dollars in healthcare costs. The use of healing markers, biochemical cues from biocompatible matrices and materials, and their correlation with wound healing has the potential to generate valuable diagnostic, prognostic, and therapeutic information. In this study, we developed a collagen-dextran oxygen-sensing biocomposite scaffold membrane in which a phosphorescent oxygen sensor was incorporated to monitor physiological oxygen using in vivo phosphorescence imaging in a preclinical mouse model of wound healing. The oxygen-sensing biocomposite scaffold membrane enabled the noninvasive and longitudinal monitoring of oxygenation changes in vivo in an approach compatible with commercially available preclinical in vivo imaging system instruments. This study provides a new and novel capability where a biocomposite material can serve as a biocompatible, biodegradable theranostic platform to promote and assess tissue oxygenation during wound healing.

Efficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in Mice.

Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy compared with control antibody plus vancomycin in two mouse models of S. aureus SSI. Therefore, monoclonal antibody-based neutralization of multiple S. aureus virulence factors may provide an adjunctive perioperative approach to combat S. aureus SSIs.

In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating.

BACKGROUND: In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating. METHODS: A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens. RESULTS: In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 10 ± 2.1 × 10 CFUs; p < 0.001), bone (6.9 × 10 ± 3.1 × 10 CFUs; p < 0.05), and implant (5.1 × 10 ± 2.2 × 10 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source. CONCLUSIONS: By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating. CLINICAL RELEVANCE: The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.

Drought alters the trophic role of an opportunistic generalist in an aquatic ecosystem.

Abiotic change can alter species interactions by modifying species' trophic roles, but this has not been well studied. Until now, bromeliad-dwelling tipulid larvae were thought to positively affect other macroinvertebrates via a facilitative processing chain. However, under drought, we found the opposite. We performed two microcosm experiments in which we factorially manipulated water level and predation by tipulids, and measured the effects on mosquito and chironomid larvae. The experiments differed in whether high water was contrasted with low or no water, allowing us to distinguish between the effects of desiccation stress (no water) and increased encounter rates due to compression of habitat or reductions in prey mobility (low and no water). We also included a caged tipulid treatment to measure any non-consumptive effects. As well as directly reducing prey survival, reductions in water level indirectly decreased chironomid and mosquito survival by altering the trophic role of tipulids. Our results suggest that increased encounter rates with prey led to tipulids becoming predatory under simulated drought, as tipulids consumed prey under both low and no water. When water level was high, tipulids exerted negative non-consumptive effects on prey survival. Because opportunistic predators are common throughout aquatic ecosystems, the effects of drought on the trophic roles of species may be widespread. Such restructuring of food webs should be considered when attempting to predict the ecological effects of environmental change.

The role of genomic approaches in diagnosis and management of primary immunodeficiency.

PURPOSE OF REVIEW: Genetic testing serves an increasingly important role in the diagnosis and management of primary immunodeficiency. In this review, the strengths and limitations of various genetic testing methods are summarized, providing a foundation for the clinical approach to achieving a molecular diagnosis. RECENT FINDINGS: Rapid advances in sequencing technology have enabled the incorporation of comprehensive genetic testing into first-line clinical diagnostics. Recent articles enable comparisons of the diagnostic utility of new testing strategies while simultaneously reminding clinicians of the strengths of traditional methods. SUMMARY: Genetic testing in primary immunodeficiency cannot be standardized, but instead needs to be personalized based on the presenting phenotype and a basic understanding of the utility of different molecular methods. These tools, when correctly employed, can achieve a molecular diagnosis and inform the natural history, prognosis, recurrence risk, and therapeutic options.