Intraoperative Fluoroscopy Versus Navigation to Determine Cup Anteversion in Direct Anterior Total Hip Replacement: A Technical Trick for Obtaining "True" Anteversion.

During acetabular cup positioning, intraoperative measurements of cup anteversion were taken using both fluoroscopy and navigation system. With the C-arm introduced at 40°, an anteroposterior view of the pelvis is taken. The C-arm is then centered over the hip, showing an anteverted cup with an approximate inclination of 40°. The axial C-arm is tilted away until the cup opening is visualized as a straight line, indicating that the beam of the fluoroscopy is aligned with the cup's anteversion. The tilt angle on the C-arm and anteversion reading on the navigation workstation were recorded. The high degree of agreement between fluoroscopic and navigation measurement of acetabular cup anteversion supports the use of fluoroscopy in settings with limited access to navigation systems in direct anterior total hip arthroplasty.

Quadriceps Tendon Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: 3-Year Clinical and Patient-Reported Outcomes.

BACKGROUND: The rate of anterior cruciate ligament (ACL) rupture in active, skeletally immature patients is increasing. Although hamstring tendon autograft (HTA) was previously deemed the gold standard, recent studies have shown HTA to have a high failure rate in this high-risk population of young competitive athletes, and quadriceps tendon autograft (QTA) has yielded excellent preliminary outcomes in some studies examining this population. PURPOSE: To evaluate 3-year clinical and patient-reported functional outcomes of primary ACL reconstruction (ACLR) with soft tissue QTA in skeletally immature patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Skeletally immature patients who underwent ACLR with a full-thickness soft tissue QTA were included. Preoperative patient and surgical data were collected. The ACLR technique was selected predicated upon skeletal age and included all-epiphyseal and complete transphyseal techniques. Patients were followed for a minimum of 2 years with successive clinical visits or were contacted via telephone. Patients who did not have minimum 2-year follow-up after 3 contact attempts via telephone were excluded. Information regarding return to sports (RTS) and concomitant or subsequent surgical procedures was collected. Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery Functional Activity Brief Scale (HSS Pedi-FABS), and Single Assessment Numeric Evaluation (SANE) scores were collected. RESULTS: Of 85 adolescent patients aged 11.1 to 17.6 years (mean age, 14.1 ± 1.2 years), 2 patients were determined to be lost to follow-up after 3 failed contact attempts. Of the patients included in this study (N = 83), 26 patients (31%) underwent all-epiphyseal and 57 patients (69%) underwent complete transphyseal ACLR. Additionally, 48 patients (58%) underwent concomitant lateral extra-articular tenodesis using the iliotibial band with a modified Lemaire technique. The mean follow-up time was 3.7 ± 1.2 years (range, 2-7 years). Twenty (24%) patients had subsequent surgical procedures, of which 3 (4%) were due to graft failures. At a mean 3-year follow-up, the mean Pedi-IKDC, HSS Pedi-FABS, and SANE scores were 90, 23, and 94 respectively; the RTS rate was 100%; and the rate of RTS at the previous level of performance was 93%. CONCLUSION: Use of a soft tissue QTA for ALCR in a high-risk skeletally immature population of athletes resulted in excellent postoperative outcomes with low rates of graft failure and high return to sport rates.

Does a delay to surgery for preoperative echocardiogram affect outcomes in patients with hip fracture?

Introduction: Delay to surgery >24 hours has been shown to correlate with mortality rates in patients with hip fracture when left untreated. Many of these patients have multiple comorbidities, including aortic stenosis (AS), and undergo workup for operative clearance, which may delay time to surgery. The purpose of this study was to examine whether preoperative echocardiogram workup affects time to surgery, complications, and mortality after operative fixation for hip fracture. Methods: Our institutional hip fracture registry was retrospectively reviewed for inclusion over a 3-year period. Patients who had a preoperative echocardiogram (yECHO) for operative clearance were compared with those who did not (nECHO). Demographic data, time to surgery, overall complication rate, and mortality at 30 days, 90 days, and 1 year were collected. Results: Two cohorts consisted of 136 yECHO patients (45.8%) and 161 nECHO patients (54.2%). Thirty-two yECHO patients (23.5%) had AS. Patients in the yECHO cohort were more likely to have a complication for any cause compared with nECHO patients (25.7% vs. 10.6%, P = 0.01) and have a higher mortality rate at 1 year (38.9% vs. 17.4%, P = 0.001). There was no association found between AS and all-cause complication (P = 0.54) or 30-day (P = 0.13) or 90-day mortality rates (P = 0.79). However, patients with AS had a significantly higher mortality rate at 1 year (45.8% vs. 25.1%, P = 0.03). Conclusion: This study reinforces the benefits of ensuring less than a 24-hour time to surgery in the setting of a hip fracture and identifies an area of preoperative management that can be further optimized to prevent unnecessary prolongation in time to surgery. Patients with known aortic stenosis are not associated with increased 30-day or 90-day mortality or all-cause complications. Surgical delays in the yECHO cohort were attributed to preoperative medical assessments, including echocardiograms and the management of comorbidities. Therefore, the selective utilization of preoperative echocardiograms is needed and should be reserved to ensure they have a definitive role in guiding the perioperative care of patients with hip fracture. Level of Evidence: III.

Pyroelectricity in poled all-organic polar polynorbornene/polydimethylsiloxane-based stretchable electrets.

Pyroelectricity in a recently developed all-organic composite electret with a polar polynorbornene-based filler and polydimethylsiloxane (PDMS) matrix has been studied with the help of thermal and dielectric techniques. Measurement of the pyroelectric p coefficient using a quasi-static periodic temperature variation at RT shows a non-linear dependence with the applied poling field, which is uncharacteristic of amorphous materials. Dielectric relaxation spectroscopy (DRS) and the thermally stimulated depolarization current (TSDC) technique reveal that this behaviour can be attributed to Maxwell-Wagner interface (MWI) polarization that occurs at the filler-matrix interface. These charges released during the onset of dipolar α and ß relaxations of the filler particles contribute majorly to the observed pyroelectricity at RT. The saturation of both MWI TSDC shoulders and spontaneous polarization at higher electric fields correlates with the p coefficient value reaching a plateau at these applied fields. A maximum p coefficient of 0.54 µC m-2 K-1 is calculated for a poling field of 30 V µm-1.

Three-Dimensional-Digital Image Correlation Methodology for Kinematic Measurements of Non-Penetrating Blunt Impacts.

Blunt force trauma remains a serious threat to many populations and is commonly seen in motor vehicle crashes, sports, and military environments. Effective design of helmets and protective armor should consider biomechanical tolerances of organs in which they intend to protect and require accurate measurements of deformation as a primary injury metric during impact. To overcome challenges found in velocity and displacement measurements during blunt impact using an integrated accelerometer and two-dimensional (2D) high-speed video, three-dimensional (3D) digital image correlation (DIC) measurements were taken and compared to the accepted techniques. A semi-spherical impactor was launched at impact velocities from 14 to 20 meters per second into synthetic ballistic gelatin to simulate blunt impacts observed in behind armor blunt trauma (BABT), falls, and sports impacts. Repeated measures Analysis of Variance resulted in no significant differences in maximum displacement (p=0.10), time of maximum displacement (p=0.21), impact velocity (p=0.13), and rebound velocity (p=0.21) between methods. The 3D-DIC measurements demonstrated equal or improved percent difference and low root-mean-square deviation compared to the accepted measurement techniques. Therefore, 3D-DIC may be utilized in BABT and other blunt impact applications for accurate 3D kinematic measurements, especially when an accelerometer or 2D lateral camera analysis is impractical or susceptible to error.

Cage enrichment to minimize aggression in part-time group-housed female breeding rabbits.

In most rabbit farms, breeding does kindle and nurse their kits in single-litter cages throughout their entire reproduction cycle. However, the protective behavior can lead to aggressive displays and injuries when the does are housed in groups. This study aimed to evaluate cage enrichment for reducing the agonistic behavior in part-time group-housed does. A total of eighty does with their 22-day-old kits were allocated to 20 multi-litter cages, with each cage housing four does and their litters for 10 days. Each multi-litter group was subjected to one of four treatments: alfalfa blocks as distraction material (A), wooden panels underneath the platforms (P), both alfalfa and wooden panels (AP), or no extra enrichment (controls, C). This experiment was replicated for three consecutive reproduction cycles. The skin injuries of the does and the kits were scored with a tagged visual analog scale before grouping and at one, three, six, eight, and 10 days after grouping. Computer vision techniques were used to continuously monitor rabbit activity and agonistic behavior (aggression and fleeing/chasing) during the first 24 h after grouping, specifically during light hours. During the first day in the group, 67.2% of the does and 13.4% of the kits acquired new injuries. This increased to 82.0 and 33.2%, respectively after 10 days in the group relative to the onset of grouping. The injury scores of the does increased toward the sixth day after grouping compared to the first (p < 0.001) and were highest on the tenth day for the kits (p < 0.001). On all the observation days, the number of injured does was higher in C compared to A (p = 0.04) and AP treatment (p = 0.005). There were no other treatment effects observed on the doe or kit skin injuries. Rabbit activity was highest after grouping but decreased after the first and second days (p < 0.001). The agonistic interactions between the does involved more fleeing/chasing behavior (62.0%) rather than aggression (38.0%). Although hierarchy fights are likely when unacquainted does are group-housed, the many animals that sustained injuries and the high injury scores confirm that part-time group housing for does is challenging and possibly inevitable. This study has shown that alfalfa, with or without wooden panels, can slightly reduce the number of injured does.

Coronal Deformity is Associated With Uptake on Single Photon Emission Computed Tomography in Patients With Low Back Pain.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) is emerging as a valuable imaging test for identifying pain generators within the lumbar spine. The relationship between radiotracer uptake on SPECT/CT and anatomic biomechanical parameters has not been previously studied. METHODS: We performed a retrospective review of all patients seen at our institution between 2021-2023 who obtained SPECT/CT scans for workup of thoracolumbar back pain. Patient data including demographic, clinical symptoms, and surgical history were collected. Radiology reports were reviewed for evidence of pathologic degeneration and increased bone metabolism on SPECT/CT. Biomechanical parameters were measured from standing scoliosis plain radiographs. Patients were stratified into two cohorts by either presence or absence of asymmetric coronal uptake on SPECT/CT. RESULTS: 160 patients met inclusion criteria. Patients were primarily male (55%) with average age 55 ± 15 years. 87 (54%) patients demonstrated asymmetric uptake on SPECT/CT. These patients were older (P < 0.001), but with similar gender, prior fusion history, sacroiliitis, adjacent segment degeneration, and pseudoarthrosis (P > 0.05). This cohort had more disc disease, facet arthropathy, and greater degree of coronal scoliosis and coronal imbalance (P < 0.001). There were significantly more sites of uptake in the asymmetric cohort, and uptake was preferentially observed in the concavity of the lumbar curve (P < 0.001). There were no significant differences in sagittal balance or spinopelvic mismatch between cohorts (P > 0.05). CONCLUSION: Asymmetric uptake on SPECT/CT was associated with coronal deformity in patients with low back pain. Further prospective studies are warranted to assess the effect of coronal deformity on pain generation.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Policy analysis for informing climate adaptation, environmental resilience, and irrigation demands in the Rio Grande Basin.

Water policymakers internationally face the challenge of adapting to climate, supporting environmental resource needs, and meeting irrigation demands for food security in the world's arid and semi-arid regions. Much recent work has assessed the economic performance of environmental river flows to support endangered species habitat protection. However, little published work to date has systematically formulated and applied methods to identify the economic performance of various policy measures that adapt to climate, support endangered species, and meet irrigation demands for water. This work's original contribution with international relevance is to address those gaps by identifying the economic performance of various water shortage sharing methods for handling climate water stress while supporting protection of critical habitat to protect the endangered Southwestern willow flycatcher (Empidonax traillii extimus) along with Willow tree (Salix bonplandiana) habitat in the middle part of the Rio Grande Basin in North America, a region facing a number of conflicts between commercial uses of water and protection of key ecological assets. It develops a hydroeconomic optimization model containing information on crop water use and endangered species requirements in that region to identify the economic performance of three climate adaptation policy scenarios for handling water shortages while respecting endangered species habitat protection requirements. Results show how water shortages as well as policy responses for handing those shortages affect the economic value of water in agriculture for food security both with and without critical habitat to support the endangered flycatcher. This work's international relevance comes from its capacity to inform policy debates on the costs of protecting endangered species habitat under various climate scenarios and climate policy adaptation measures. Findings provide a general framework to address existing gaps in understanding and measuring the economic performance of measures to promote environmental resilience.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Biomechanical Predictors of Sacroiliac Joint Uptake on Single-Photon Emission Computed Tomography/Computed Tomography.

OBJECTIVE: Single-photon emission computed tomography/computed tomography (SPECT/CT) is an emerging imaging modality that identifies sites of heightened bone metabolism in response to increased stresses. The relationship between sacroiliac (SI) joint radiotracer uptake and anatomic biomechanical parameters is poorly understood. METHODS: Adult patients with SPECT/CT scans performed at our institution between 2021 and 2023 for the workup of low back pain were included. Patient charts were reviewed for demographic factors including age, gender, and prior thoracolumbar fusion history. Biomechanical spinopelvic parameters were measured from standing scoliosis radiographs. SPECT/CT scans were reviewed for uptake at the SI joint. Patients were stratified into 2 cohorts; patients with SI uptake greater than iliac crest uptake were designated "hot," whereas those with less or equal uptake were labeled "cold." RESULTS: One-hundred and sixty patients met inclusion criteria. Patients were slightly more male (55%) with average age 55 ± 14.9 years. Sixty-eight patients (43%) had evidence of increased SI activity. Interrater reliability showed substantial agreement (kappa = 0.62). The hot cohort demonstrated greater pelvic incidence (54.8 ± 14.0 degrees vs. 51.0 ± 11.0 degrees, P = 0.031) and pelvic tilt (20.8 ± 9.5 degrees vs. 18.4 ± 8.6 degrees, P =0.047) compared with the cold cohort. Patients were otherwise similar between cohorts (P > 0.05). CONCLUSIONS: Increased pelvic incidence and pelvic tilt angles are associated with SPECT/CT uptake at the SI joint, which may reflect altered biomechanics at the spinopelvic junction. SPECT/CT may be a valuable tool to assess SI degeneration. Future studies are warranted to better characterize the clinical applications of these findings.

Melatonin decreases human adipose tissue insulin sensitivity.

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

Using the Equatorial Talar Line as a Radiographic Predictor of Sanders Type 3 and 4 Calcaneus Fractures and Lateral Wall Blowout.

OBJECTIVE: To assess the equatorial talar line (ETL) as a sensitive radiographic parameter to predict Sanders type III and IV fractures and the presence of lateral wall blowout. METHODS: Reliability of the ETL was assessed using the intraclass correlation coefficient (ICC) and receiver operating curve (ROC) to predict sensitivity. Using lateral ankle radiographs, raters determined whether the calcaneal tuberosity was "above" (predicting Sanders type I or II) or "below" (predicting Sanders type III or IV and lateral wall blowout). RESULTS: In determining the "above" or "below" location of the ETL, the calculated ICC was 1.0 for each session. As a predictor of Sanders fracture classification type, the calculated ICC was 0.93 for the first session and 0.89 for the second session for an overall ICC of 0.91. As a predictor of Sanders fracture type, ROC analysis yielded an overall sensitivity of 0.82. As a predictor of lateral wall blowout, ROC analysis yielded an overall sensitivity of 0.81. CONCLUSION: The ETL is a reproducible radiographic parameter that can be reliably used to crudely predict between Sanders type I or II (ETL is "above") and Sanders type III or IV (ETL is "below") calcaneus fractures as well as the presence of lateral wall blowout.

Are all ADHD medications created equal? Exploring the differences that enable evening dosing.

With more than 30 available stimulant medications, choosing among therapeutic options for attention-deficit/hyperactivity disorder (ADHD) has become increasingly complex and patient specific. All ADHD stimulants owe their action to variants of either amphetamine or methylphenidate, yet formulation and delivery system differences create unique pharmacokinetic and clinical profiles for each medication. A benefit of the diversity within ADHD pharmacotherapy is that it facilitates tailoring treatment to meet patient needs. Historically, there has been a constant among long-acting stimulant options, regardless of formulation, which was morning dosing. The introduction of delayed-release and extended-release methylphenidate (DR/ER-MPH) is the first long-acting stimulant that patients take in the evening, with the clinical effect delayed until awakening in the morning. This paradigm shift has generated questions among clinicians and continued interest in real-world experience and data. This review used available clinical data, real-world evidence, emerging analyses, and clinical experience to evaluate the characteristics of DR/ER-MPH and its clinical utility within the greater context of ADHD medications and to provide clinicians with practical guidance on the use of DR/ER-MPH in children, adolescents, and adults with ADHD.

The effect of experimentally-induced sleep fragmentation and estradiol suppression on neurobehavioral performance and subjective sleepiness in pre-menopausal women.

STUDY OBJECTIVES: Menopause is associated with nighttime sleep fragmentation, declining estradiol and impaired cognition. In a model of pharmacologically-induced estradiol suppression mimicking menopause, we examined the impact of menopause-pattern sleep fragmentation on daytime neurobehavioral performance and sleepiness in premenopausal women. METHODS: Twenty premenopausal women completed two 5-night inpatient studies in the mid-to-late follicular phase (estrogenized) and after pharmacological estradiol suppression (hypo-estrogenized). During each study, participants had an uninterrupted 8-hour sleep opportunity for two nights, followed by three nights where sleep was experimentally fragmented to mimic menopause-pattern sleep disturbance, and during which the sleep opportunity was extended to prevent shortening of the sleep duration. Neurobehavioral performance and subjective sleepiness were measured using the Psychomotor Vigilance Task and Karolinska Sleepiness Scale (KSS). RESULTS: Compared to unfragmented sleep, sleep fragmentation increased attentional lapses (+0.6 lapses, p<0.05), slowed reaction time (+9.4 milliseconds, p<0.01), and increased daytime sleepiness (+0.5 KSS score, p<0.001). Estradiol suppression increased attentional lapses (+0.8; p<0.001) and reaction time (+12.3, p<0.01) but did not significantly affect daytime sleepiness. The effect of sleep fragmentation on neurobehavioral performance differed by estradiol state, such that the adverse effects of sleep fragmentation on attentional lapses (+0.9, trend p=0.06) and reaction time (+15, p<0.05) were observed only when estrogenized. CONCLUSIONS: Menopause-pattern sleep fragmentation and estradiol suppression worsened neurobehavioral performance and daytime sleepiness, even while sleep duration was not reduced. The adverse effects of sleep fragmentation in the context of an adequate sleep duration highlight the importance of sleep continuity as a vital aspect of good sleep health.

Epidemiology, Etiology, and Pathophysiology of Pulmonary Embolism.

Over the last 20 years, there has been a progressive increase in the incidence of pulmonary embolism (PE) diagnosis in the United States, Europe, and Australia. Increased use of computed tomography pulmonary angiography has likely contributed in part to this rising incidence. However, it is pertinent to note that the burden of comorbidities associated with PE, such as malignancy, obesity, and advanced age, has also increased over the past 20 years. Time-trend analysis in North American, European, and Asian populations suggests that mortality rates associated with PE have been declining. The reported improved survival rates in PE over the past 20 years are likely, at least in part, to be the result of better adherence to guidelines, improved risk stratification, and enhanced treatment. Factors contributing to the development of venous thromboembolism (VTE) include stasis of blood, hypercoagulability, endothelial injury, and inflammation. In 70 to 80% of cases of PE, the thrombi embolizes from the proximal deep veins of the lower extremities and pelvis. Strong risk factors for VTE include lower extremity fractures and surgeries, major trauma, and hospitalization within the previous 3 months for acute myocardial infarction or heart failure with atrial fibrillation. Acute PE causes several pathophysiological responses including hypoxemia and right ventricle (RV) failure. The latter is a result of pulmonary artery occlusion and associated vasoconstriction. Hemodynamic compromise from RV failure is the principal cause of poor outcome in patients with acute PE.

Safety of tenofovir alafenamide in people with HIV who experienced proximal renal tubulopathy on tenofovir disoproxil.

Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

Transcriptomic and developmental effects of persistent organic pollutants in sentinel fishes collected near an arctic formerly used defense site.

Alaska contains over 600 formerly used defense (FUD) sites, many of which serve as point sources of pollution. These sites are often co-located with rural communities that depend upon traditional subsistence foods, especially lipid-rich animals that bioaccumulate and biomagnify persistent organic pollutants (POPs). Many POPs are carcinogenic and endocrine-disrupting compounds that are associated with adverse health outcomes. Therefore, elevated exposure to POPs from point sources of pollution may contribute to disproportionate incidence of disease in arctic communities. We investigated PCB concentrations and the health implications of POP exposure in sentinel fishes collected near the Northeast Cape FUD site on Sivuqaq (St. Lawrence Island), Alaska. Sivuqaq residents are almost exclusively Yupik and rely on subsistence foods. At the request of the Sivuqaq community, we examined differential gene expression and developmental pathologies associated with exposure to POPs originating at the Northeast Cape FUD site. We found significantly higher levels of PCBs in Alaska blackfish (Dallia pectoralis) collected from contaminated sites downstream of the FUD site compared to fish collected from upstream reference sites. We compared transcriptomic profiles and histopathologies of these same blackfish. Blackfish from contaminated sites overexpressed genes involved in ribosomal and FoxO signaling pathways compared to blackfish from reference sites. Contaminated blackfish also had significantly fewer thyroid follicles and smaller pigmented macrophage aggregates. Conversely, we found that ninespine stickleback (Pungitius pungitius) from contaminated sites exhibited thyroid follicle hyperplasia. Despite our previous research reporting transcriptomic and endocrine differences in stickleback from contaminated vs. reference sites, we did not find significant differences in kidney or gonadal histomorphologies. Our results demonstrate that contaminants from the Northeast Cape FUD site are associated with altered gene expression and thyroid development in native fishes. These results are consistent with our prior work demonstrating disruption of the thyroid hormone axis in Sivuqaq residents.