Effects of low temperature on growth and metabolism of larval green sturgeon (Acipenser medirostris) across early ontogeny.

Southern Distinct Population Segment (sDPS) green sturgeon spawn solely in one stretch of the Sacramento River in California. Management of this spawning habitat is complicated by cold water temperature requirements for the conservation of winter-run Chinook salmon. This study assessed whether low incubation and rearing temperatures resulted in carryover effects across embryo to early juvenile life stages on scaling relationships in growth and metabolism in northern DPS green sturgeon used as a proxy for sDPS green sturgeon. Fish were incubated and reared at 11 °C and 15 °C, with a subset experiencing a reciprocal temperature transfer post-hatch, to assess recovery from cold incubation or to simulate a cold-water dam release which would chill rearing larvae. Growth and metabolic rate of embryos and larvae were measured to 118 days post hatch. Reciprocal temperature transfers revealed a greater effect of low temperature exposure during larval rearing rather than during egg incubation. While 11 °C eggs hatched at a smaller length, log-transformed length-weight relationships showed that these differences in developmental trajectory dissipated as individuals achieved juvenile morphology. However, considerable size-at-age differences persisted between rearing temperatures, with 15 °C fish requiring 60 days post-hatch to achieve 1 g in mass, whereas 11 °C fish required 120 days to achieve 1 g, resulting in fish of the same age at the completion of the experiment with a ca. 37-fold difference in weight. Consequently, our study suggests that cold rearing temperatures have far more consequential downstream effects than cold embryo incubation temperatures. Growth delays from 11 °C rearing temperatures would greatly increase the period of vulnerability to predation in larval green sturgeon. The scaling relationship between log-transformed whole-body metabolism and mass exhibited a steeper slope and thus an increased oxygen requirement with size in 11 °C reared fish, potentially indicating an energetically unsustainable situation. Understanding how cold temperatures affect green sturgeon ontogeny is necessary to refine our larval recruitment estimations for this threatened species.

Optimization of diastereomeric dihydropyridines as antimalarials.

The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC50 < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.

Outcomes of treatment of patella fractures in children and adolescents.

Purpose: The purpose of this study is to assess clinical and functional outcomes in separate cohorts of operatively and nonoperatively managed pediatric patella fractures. Methods: A retrospective review was completed for patients aged 5-19 years treated for a unilateral patella fracture at a single pediatric level-1 trauma center. Patients were excluded for osteochondral fracture associated with patellar dislocation, polytrauma presentation with additional fractures, or <3 months of clinical follow-up. Functional outcomes were assessed via the Pediatric International Knee Documentation Committee form and the Marx Knee Activity Scale. Results: A total of 53 patients met inclusion criteria; 30 patients were treated operatively and 23 patients were treated nonoperatively. Patients with patellar sleeve/pole fractures were significantly younger by 5.2 years (p < 0.01) and presented with greater variability in mechanism of injury (p < 0.01). The nonoperative cohort achieved bony healing and returned to sports at a median (interquartile range) of 1.7 (1.2-2.3) months and 2.8 (2.3-3.3) months, respectively, post-injury. The operative group achieved bony healing and returned to sports at 2.8 (2.1-3.5) months and 5.9 (4.0-7.1) months, respectively, following surgery. Median (interquartile range) Pediatric International Knee Documentation Committee and Marx scores were 98 (89-100) and 14 (10-16), respectively, for the nonoperative group, and 92 (84-99) and 13 (12-16), respectively, for the operative group. No significant differences in patient-reported outcomes were observed between fracture patterns or treatment cohorts. Conclusion: Pediatric and adolescent patients sustaining patella fractures reported long-term functional outcomes comparable to normative values, across multiple fracture patterns and with appropriate operative and nonoperative treatment. Fractures requiring surgery were expectedly associated with slower healing and return to sport timelines. Level of evidence: Therapeutic Level III.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder.

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

MatchMaps: non-isomorphous difference maps for X-ray crystallography.

Conformational change mediates the biological functions of macromolecules. Crystallographic measurements can map these changes with extraordinary sensitivity as a function of mutations, ligands and time. A popular method for detecting structural differences between crystallographic data sets is the isomorphous difference map. These maps combine the phases of a chosen reference state with the observed changes in structure factor amplitudes to yield a map of changes in electron density. Such maps are much more sensitive to conformational change than structure refinement is, and are unbiased in the sense that observed differences do not depend on refinement of the perturbed state. However, even modest changes in unit-cell properties can render isomorphous difference maps useless. This is unnecessary. Described here is a generalized procedure for calculating observed difference maps that retains the high sensitivity to conformational change and avoids structure refinement of the perturbed state. This procedure is implemented in an open-source Python package, MatchMaps, that can be run in any software environment supporting PHENIX [Liebschner et al. (2019). Acta Cryst. D75, 861-877] and CCP4 [Agirre et al. (2023). Acta Cryst. D79, 449-461]. Worked examples show that MatchMaps 'rescues' observed difference electron-density maps for poorly isomorphous crystals, corrects artifacts in nominally isomorphous difference maps, and extends to detecting differences across copies within the asymmetric unit or across altogether different crystal forms.

Abstinence beliefs in early adolescence and sexual risk behavior two years later.

INTRODUCTION: The United States has the highest teen pregnancy rate and sexually transmitted infection rates among developed countries. One common approach that has been implemented to reduce these rates is abstinence-only-until-marriage programs that advocate for delaying sexual intercourse until marriage. These programs focus on changing adolescents' beliefs toward abstinence until marriage; however, it is unclear whether adolescents' beliefs about abstinence predict their sexual behavior, including sexual risk behavior (SRB). An alternative approach may be encouraging youth to delay their sexual debut until they reach the age of maturity, but not necessarily until marriage. METHODS: To address this question, we compare the longitudinal association between abstinence beliefs (i.e., abstaining completely until marriage) and beliefs about delayed sexual debut with subsequent SRB 24 months later. The harmonized data set included 4620 (58.2% female, Mage = 13.0, SDage = 0.93) participants from three randomized controlled trials attending 44 schools in the southern United States. Negative binomial regressions were employed to examine the association of abstinence until marriage beliefs and beliefs regarding delaying sex with SRB. RESULTS: We identified that beliefs supporting delaying sex until an age of maturity were associated with lower odds of engaging in SRB, such as having multiple sex partners and frequency of condomless sex, for both sexes. However, stronger abstinence beliefs had no significant associations with all SRB outcomes. CONCLUSIONS: Findings suggest prevention programming that focuses on encouraging youth to delay sex until an appropriate age of maturity may be more effective at preventing SRB and consequent negative sexual health outcomes.

Effect of dietary antioxidants on free radical damage in dogs and cats.

Alpha-tocopherol (vitamin E) is an antioxidant that is largely involved in immune defense and enhancing the ability of biological systems to respond to oxidative stress. During the process of free radical scavenging, vitamin C supports the regeneration of vitamin E. Although the functions of antioxidants and their importance have been widely studied, the intricate interplay between antioxidants has yet to be fully elucidated, especially in dogs and cats. As such, the objective of the present study was to determine the effect of a combination of dietary antioxidants on DNA damage and antioxidant status in dogs and cats. Forty adult mixed-breed dogs and 40 adult domestic shorthair cats were randomly assigned to one of four treatment groups per species. Dogs and cats remained in these groups for the 84-d duration of the study. The food differed in antioxidant supplementation with the control food meeting all of the Association of American Feed Control Officials requirements for complete and balanced nutrition, including sufficient vitamin E to exceed the published minimum. The treatment diets were targeted to include either 500, 1,000, or 1,500 IU vitamin E/kg as well as 100 ppm of vitamin C and 1.5 ppm of ß-carotene in the food. The effect of vitamin E supplementation level on serum vitamin E concentration, DNA damage, and total antioxidant power was evaluated. Feeding diets enriched with antioxidants resulted in an increased (P < 0.05) circulating vitamin E concentration, increased (P < 0.05) immune cell protection, reduced (P < 0.05) DNA damage in dogs, and an improved (P < 0.05) antioxidant status. Overall, these data demonstrated that feeding a dry kibble with an antioxidant blend inclusive of vitamin E, vitamin C, and ß-carotene enhanced cell protection and improved antioxidant status in dogs and cats.

Animals have an impressive array of defenses to excessive reactive oxygen species in the body. The antioxidant defense system is complex and sophisticated. vitamin E, vitamin C, and ß-carotene are known to scavenge free radicals that are created during times of oxidative stress. To evaluate the effect of the various antioxidants, dogs and cats were fed one of four diets for 84 d. Diets included a control group that had vitamin E concentrations that exceeded regulatory minimums and four treatment groups that were targeted to include 500, 1,000, or 1,500 IU vitamin E/kg as well as 100 ppm of vitamin C and 1.5 ppm of ß-carotene in the food. To assess the effectiveness of the different vitamin E concentrations provided in the foods, circulating vitamin E, DNA damage, and total antioxidant power were assessed. Results from the parameters assessed showed that dogs and cats benefit from supplementing their diet with a blend of antioxidants targeted to include 100 ppm of vitamin C, 1.5 ppm of ß-carotene, and have varying benefits to increased vitamin E/kg in the food.

Increased lipogenesis and lipidosis of gallbladder epithelium in dogs with gallbladder mucocele formation.

BACKGROUND: Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown. METHODS: A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium. RESULTS: Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism. CONCLUSION: Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.

Effects of acclimation temperature and feed restriction on the metabolic performance of green sturgeon.

Green sturgeon (Acipenser medirostris) are an anadromous threatened species of sturgeon found along the Pacific coast of North America. The southern distinct population segment only spawns in the Sacramento River and is exposed to water temperatures kept artificially cold for the conservation and management of winter-run Chinook salmon (Oncorhynchus tshawytscha). Past research has demonstrated costs of cold-water rearing including reduced growth rates, condition and survivorship of juvenile green sturgeon. Our research investigates how the stressors of water temperature and food limitation influence the metabolic performance of green sturgeon. We reared green sturgeon at two acclimation temperatures (13 and 19°C) and two ration amounts (100% and 40% of optimal feed). We then measured the routine and maximum metabolic rates (RMR and MMR, respectively) of sturgeon acclimated to these rearing conditions across a range of acute temperature exposures (11 to 31°C). Among both temperature acclimation treatments (13 or 19°C), we found that feed restriction reduced RMR across a range of acute temperatures. The influence of feed restriction on RMR and MMR interacted with acclimation temperature. Fish reared at 13°C preserved their MMR and aerobic scope (AS) despite feed restriction, while fish fed reduced rations and acclimated to 19°C showed reduced MMR and AS capacity primarily at temperatures below 16°C. The sympatry of threatened green sturgeon with endangered salmonids produces a conservation conflict, such that cold-water releases for the conservation of at-risk salmonids may constrain the metabolic performance of juvenile green sturgeon. Understanding the impacts of environmental conditions (e.g. temperature, dissolved oxygen) on ecological interactions of green sturgeon will be necessary to determine the influence of salmonid-focused management.

The influence of oviposition status on measures of transmission potential in malaria-infected mosquitoes depends on sugar availability.

BACKGROUND: Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organism's oviposition status also influence their nutrient requirement from the environment. Yet, studies that measure transmission potential (vectorial capacity or competence) of mosquito-borne parasites rarely consider whether the rates of parasite replication and development could be influenced by these constraints resulting from whether mosquitoes have completed their gonotrophic cycle. METHODS: Anopheles stephensi mosquitoes were infected with Plasmodium berghei, the rodent analog of human malaria, and maintained on 1% or 10% dextrose and either provided oviposition sites ('oviposited' herein) to complete their gonotrophic cycle or forced to retain eggs ('non-oviposited'). Transmission potential in the four groups was measured up to 27 days post-infection as the rates of (i) sporozoite appearance in the salivary glands ('extrinsic incubation period' or EIP), (ii) vector survival and (iii) sporozoite densities. RESULTS: In the two groups of oviposited mosquitoes, rates of sporozoite appearance and densities in the salivary glands were clearly dependent on sugar availability, with shorter EIP and higher sporozoite densities in mosquitoes fed 10% dextrose. In contrast, rates of appearance and densities in the salivary glands were independent of sugar concentrations in non-oviposited mosquitoes, although both measures were slightly lower than in oviposited mosquitoes fed 10% dextrose. Vector survival was higher in non-oviposited mosquitoes. CONCLUSIONS: Costs to parasite fitness and vector survival were buffered against changes in nutritional availability from the environment in non-oviposited but not oviposited mosquitoes. Taken together, these results suggest vectorial capacity for malaria parasites may be dependent on nutrient availability and oviposition/gonotrophic status and, as such, argue for more careful consideration of this interaction when estimating transmission potential. More broadly, the complex patterns resulting from physiological (nutrition) and evolutionary (egg-retention) trade-offs described here, combined with the ubiquity of selective oviposition behavior, implies the fitness of vector-borne pathogens could be shaped by selection for these traits, with implications for disease transmission and management. For instance, while reducing availability of oviposition sites and environmental sources of nutrition are key components of integrated vector management strategies, their abundance and distribution are under strong selection pressure from the patterns associated with climate change.

Examining the Relation Between Early Violence Exposure and Firearm-Related Experiences in Emerging Adulthood: A Longitudinal Cohort Study.

Firearms are a leading cause of death among adolescents and young adults in the United States. Early exposure to violence, as a victim or witness, is associated with increased risk of firearm-related experiences, including carrying and threatening others with a gun. These experiences, in turn, increase the risk of both fatal and non-fatal firearm injuries. Using an ethnically diverse sample of emerging adults, we build on prior research by examining the link between early violence exposure at multiple contexts of the social-ecological model and multiple firearm-related experiences (i.e., firearm-threatening victimization, firearm-threatening perpetration, and firearm carriage). We analyzed data from a 10-year longitudinal study of 1042 youth in the Southern United States. Experiencing childhood physical abuse was associated with both firearm-threatening victimization and perpetration in emerging adulthood. Additionally, exposure to neighborhood and interparental violence were linked to threatening others with firearms and carrying firearms, respectively. Counter to expectations, bullying victimization did not emerge as a predictor of any firearm-related experiences. Findings highlight the importance of cross-cutting violence prevention efforts to prevent high-risk firearm-related behaviors among emerging adults. Programs for children and adolescents that address these types of violence exposure should highlight coping skills and sources of positive social support to bolster protective factors against firearm-related outcomes.

Chromosomal instability induced in cancer can enhance macrophage-initiated immune responses that include anti-tumor IgG.

Solid tumors generally exhibit chromosome copy number variation, which is typically caused by chromosomal instability (CIN) in mitosis. The resulting aneuploidy can drive evolution and associates with poor prognosis in various cancer types as well as poor response to T-cell checkpoint blockade in melanoma. Macrophages and the SIRPα-CD47 checkpoint are understudied in such contexts. Here, CIN is induced in poorly immunogenic B16F10 mouse melanoma cells using spindle assembly checkpoint MPS1 inhibitors that generate persistent micronuclei and diverse aneuploidy while skewing macrophages toward a tumoricidal 'M1-like' phenotype based on markers and short-term anti-tumor studies. Mice bearing CIN-afflicted tumors with wild-type CD47 levels succumb similar to controls, but long-term survival is maximized by SIRPα blockade on adoptively transferred myeloid cells plus anti-tumor monoclonal IgG. Such cells are the initiating effector cells, and survivors make de novo anti-cancer IgG that not only promote phagocytosis of CD47-null cells but also suppress tumor growth. CIN does not affect the IgG response, but pairing CIN with maximal macrophage anti-cancer activity increases durable cures that possess a vaccination-like response against recurrence.

Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

Community-Level Factors As Positive and Negative Correlates of Sexual Aggression Perpetration Among Adolescent Boys.

Often, perpetrators of sexual violence first aggress in their teens. Presently, very little is known about environmental factors that may influence adolescents' engagement in sexual aggression. Drawing upon data collected at 27 high schools in the Northeast United States, this study is the first to test the association between community-level factors and male adolescents' sexual aggression. A series of backward linear regressions determined that 10 of 19 community variables were associated with males' sexual aggression, which were then used to generate a ratio of positive to negative correlates of sexual aggression for each high school. In multilevel analyzes, as hypothesized, the ratio of positive to negative correlates was positively associated with schools' sexual aggression perpetration rates. We discuss the study's implications for future sexual assault research and prevention interventions.

Extended blood stage sensitivity profiles of Plasmodium cynomolgi to doxycycline and tafenoquine, as a model for Plasmodium vivax.

Testing Plasmodium vivax antimicrobial sensitivity is limited to ex vivo schizont maturation assays, which preclude determining the IC50s of delayed action antimalarials such as doxycycline. Using Plasmodium cynomolgi as a model for P. vivax, we determined the physiologically significant delayed death effect induced by doxycycline [IC50(96 h), 1,401 ± 607 nM]. As expected, IC50(96 h) to chloroquine (20.4 nM), piperaquine (12.6 µM), and tafenoquine (1,424 nM) were not affected by extended exposure.

Load carriage changes tibiofemoral arthrokinematics during ambulatory tasks in recruit-aged women.

The introduction of women into U.S. military ground close combat roles requires research into sex-specific effects of military training and operational activities. Knee osteoarthritis is prevalent among military service members; its progression has been linked to occupational tasks such as load carriage. Analyzing tibiofemoral arthrokinematics during load carriage is important to understand potentially injurious motion and osteoarthritis progression. The study purpose was to identify effects of load carriage on knee arthrokinematics during walking and running in recruit-aged women. Twelve healthy recruit-aged women walked and ran while unloaded (bodyweight [BW]) and carrying additional + 25%BW and + 45%BW. Using dynamic biplane radiography and subject-specific bone models, tibiofemoral arthrokinematics, subchondral joint space and center of closest contact location between subchondral bone surfaces were analyzed over 0-30% stance (separate one-way repeated measures analysis of variance, load by locomotion). While walking, medial compartment contact location was 5% (~ 1.6 mm) more medial for BW than + 45%BW at foot strike (p = 0.03). While running, medial compartment contact location was 4% (~ 1.3 mm) more lateral during BW than + 25%BW at 30% stance (p = 0.04). Internal rotation was greater at + 45%BW compared to + 25%BW (p < 0.01) at 30% stance. Carried load affects tibiofemoral arthrokinematics in recruit-aged women. Prolonged load carriage could increase the risk of degenerative joint injury in physically active women.

Knee Flexion Angle of Fixation During Anterolateral Ligament Reconstruction or Lateral Extra-articular Tenodesis: A Systematic Review and Meta-analysis of Lateral Extra-articular Reinforcement Techniques Performed in Conjunction With ACL Reconstruction.

Background: Anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) is being used more frequently in conjunction with anterior cruciate ligament reconstruction (ACLR). However, the knee flexion angle at which fixation of ALLR or LET is performed during the procedure is quite variable based on existing technique descriptions. Purpose/Hypothesis: The purpose of this study was to identify whether flexion angle at the time of ALLR/LET fixation affected postoperative outcomes in a clinical population. It was hypothesized that ALLR/LET fixation at low versus high flexion angles would lead to no statistically significant differences in patient-reported outcome measures and graft failure rates. Study Design: Systematic review; Level of evidence, 4. Methods: The PubMed, Embase, and Cochrane Library databases were searched according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify published clinical studies of ACLR with ALLR/LET in which the knee flexion angle at the time of ALLR/LET was reported. A priori, low flexion was defined as 0° to 30°, and high flexion was defined as 60° to 90°. Studies were excluded if the flexion angle was between 31° and 59° because these angles constituted neither low nor high flexion angles and including them in an analysis of high versus low flexion angle at fixation would have biased the study results toward the null. The overall risk of bias was assessed using the Newcastle-Ottawa Scale. The pooled results of the studies were analyzed using the International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores, along with reported graft failure rates. Results: A total of 32 clinical studies (5230 patients) met inclusion criteria: 22 studies (1999 patients) in the low-flexion group and 10 studies (3231 patients) in the high-flexion group. The median Newcastle-Ottawa Scale score was 6. Comparisons of patients with a low flexion angle versus a high flexion angle demonstrated no differences in the IKDC (P = .84), Lysholm (P = .67), or Tegner (P = .44) scores or in graft failure (3.4% vs 4.1%, respectively; P = .69). Conclusion: The results of this review indicated that ACLR performed in conjunction with ALLR/LET provides good to excellent patient-reported outcomes and low graft failure rates when ALLR/LET fixation is performed in either low or high knee flexion.

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Infants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. METHODS: Infants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. RESULTS: Of 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. CONCLUSIONS: Among infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Prevalence and Predictors of Concomitant Meniscal Surgery During Pediatric and Adolescent ACL Reconstruction: Analysis of 4729 Patients Over 20 Years at a Tertiary-Care Regional Children's Hospital.

Background: The rate of concomitant meniscal procedures performed in conjunction with anterior cruciate ligament (ACL) reconstruction is increasing. Few studies have examined these procedures in high-risk pediatric cohorts. Hypotheses: That (1) the rates of meniscal repair compared with meniscectomy would increase throughout the study period and (2) patient-related factors would be able to predict the type of meniscal operation, which would differ according to age. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: Natural language processing was used to extract clinical variables from notes of patients who underwent ACL reconstruction between 2000 and 2020 at a single institution. Patients were stratified to pediatric (5-13 years) and adolescent (14-19 years) cohorts. Linear regression was used to evaluate changes in the prevalence of concomitant meniscal surgery during the study period. Logistic regression was used to determine predictors of the need for and type of meniscal procedure. Results: Of 4729 patients (mean age, 16 ± 2 years; 54.7% female) identified, 2458 patients (52%) underwent concomitant meniscal procedures (55% repair rate). The prevalence of lateral meniscal (LM) procedures increased in both pediatric and adolescent cohorts, whereas the prevalence of medial meniscal (MM) repair increased in the adolescent cohort (P = .02). In the adolescent cohort, older age was predictive of concomitant medial meniscectomy (P = .031). In the pediatric cohort, female sex was predictive of concomitant MM surgery and of undergoing lateral meniscectomy versus repair (P≤ .029). Female sex was associated with decreased odds of concomitant LM surgery in both cohorts (P≤ .018). Revision ACLR was predictive of concomitant MM surgery and of meniscectomy (medial and lateral) in the adolescent cohort (P < .001). Higher body mass index was associated with increased odds of undergoing medial meniscectomy versus repair in the pediatric cohort (P = .03). Conclusion: More than half of the young patients who underwent ACLR had meniscal pathology warranting surgical intervention. The prevalence of MM repair compared with meniscectomy in adolescents increased throughout the study period. Patients who underwent revision ACLR were more likely to undergo concomitant meniscal surgeries, which were more often meniscectomy. Female sex had mixed effects in both the pediatric and adolescent cohorts.

Biomechanical analysis of complications following T10-Pelvis spinal fusion: A population based computational study.

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are challenging complications of long fusion constructs for the treatment of adult spinal deformity. The objective of this study is to understand the biomechanical stresses proximal to the upper instrumentation of a T10-pelvis fusion in a large patient cohort. The pre-fusion models were subject-specific thoracolumbar spine models that incorporate the height, weight, spine curvature, and muscle morphology of 250 individuals from the Framingham Heart Study Multidetector CT Study. To create post-fusion models, the subject-specific models were further modified to eliminate motion between the intervertebral joints from T10 to the pelvis. OpenSim analysis tools were used to calculate the medial lateral shear force, anterior posterior shear force, and compressive force on the T9 vertebra during the static postures. Differences between pre-fusion and post-fusion T9 biomechanics were consistent between increased segmental mobility and unchanged segmental mobility conditions. For all static postures, compression decreased (p < 0. 0005). Anterior-posterior shear force significantly increased (p < 0. 0005) during axial twist and significantly increased (p < 0. 0005) during trunk flexion. Medial lateral shear force significantly increased (p < 0. 0005) during axial twist. This computational study provided the first use of subject-specific models to investigate the biomechanics of long spinal fusions. Patients undergoing T10-Pelvis fusion were predicted to have increased shear forces and decreased compressive force at the T9 vertebra, independent of change in segmental mobility. The computational model shows potential for the investigation of spinal fusion biomechanics to reduce the risk of PJK or PJF.