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In this case series, we present 5 cases of autoimmune rheumatic disease onset shortly after receiving mRNA vaccination against coronavirus disease 2019 (COVID-19).We identified 5 patients from Brooke Army Medical Center who developed new manifestations of rheumatic disease following the second dose of the Pfizer-BioNTech or Moderna COVID-19 vaccinations. All patients were initially seen in primary care and then referred to rheumatology for further evaluation and management. Clinical data were obtained through review of the electronic medical record.Three cases involve elderly women with insidious onset of symmetric wrist and hand polyarthritis with seropositivity for rheumatoid factor. One case involves an elderly woman with a subacute onset of lower extremity-predominant, symmetric polyarthritis. One case involves an elderly man with insidious onset of bilateral shoulder and hip stiffness and arthralgias in the setting of elevated erythrocyte sedimentation rate and a rapid response to glucocorticoid therapy.Whether there exists a causal or contributory relationship between COVID-19 mRNA vaccination and the development of autoimmune rheumatic disease remains to be determined. Ultimately, further research is needed to establish if there is a true connection between the two.

There have been no studies comparing 2% and 4% chlorhexidine gluconate (CHX) for vaginal surgical site preparation despite both commonly being used.The primary objective was to assess the noninferiority of 2% CHX versus 4% CHX to reduce bacterial contamination rates at 60 minutes after surgical preparation of the vagina. Secondary objectives were to assess differences in colony-forming units and the sensation of postoperative vaginal burning and pain.This is a single-blinded randomized controlled trial of women who underwent vaginal prolapse surgery. Study participants were randomized into 2 groups: 2% CHX versus 4% CHX. Two vaginal bacterial cultures were collected: (1) preoperatively before vaginal preparation and (2) intraoperatively at 60 minutes. A questionnaire on vaginal pain and burning was administered preoperatively and postoperatively. For our sample size, assuming that 2% CHX would have double the contamination rate of 4% CHX, 26 participants were needed per group to demonstrate noninferiority.Sixty-one women participated in the study. There were no differences in baseline demographics, length of surgery, or surgical procedures. For our primary outcome, the postpreparation contamination rates were 7% for 2% CHX versus 10% for 4% CHX, with a difference of 3% ( P = 0.52). This difference did meet the criteria for noninferiority. Secondary outcomes were not different between groups.Two percent CHX is noninferior to 4% CHX in reducing vaginal bacterial contamination at 60 minutes after vaginal surgical site preparation, with low rates of postpreparation contamination and vaginal discomfort.

We evaluated the contributions of maternal age, year of death (period), and year of birth (cohort) on trends in hypertension-related maternal deaths in the United States. We undertook a sequential time series analysis of 155 710 441 live births and 3287 hypertension-related maternal deaths in the United States, 1979 to 2018. Trends in pregnancy-related mortality rate (maternal mortality rate [MMR]) due to chronic hypertension, gestational hypertension, and preeclampsia/eclampsia, were examined. MMR was defined as death during pregnancy or within 42 days postpartum due to hypertension. Trends in overall and race-specific hypertension-related MMR based on age, period, and birth cohort were evaluated based on weighted Poisson models. Trends were also adjusted for secular changes in obesity rates and corrected for potential death misclassification. During the 40-year period, the overall hypertension-related MMR was 2.1 per 100 000 live births, with MMR being almost 4-fold higher among Black compared with White women (5.4 [n=1396] versus 1.4 [n=1747] per 100 000 live births). Advancing age was associated with a sharp increase in MMR at ≥15 years among Black women and at ≥25 years among White women. Birth cohort was also associated with increasing MMR. Preeclampsia/eclampsia-related MMR declined annually by 2.6% (95% CI, 2.2–2.9), but chronic hypertension–related MMR increased annually by 9.2% (95% CI, 7.9–10.6). The decline in MMR was attenuated when adjusted for increasing obesity rates. The temporal burden of hypertension-related MMR in the United States has increased substantially for chronic hypertension–associated MMR and decreased for preeclampsia/eclampsia-associated MMR. Nevertheless, deaths from hypertension continue to contribute substantially to maternal deaths.

Suicide is a leading cause of death among children and adolescents, and research has shown a significant increase in the rates of emergency department (ED) visits because of suicide ideation and attempts for children younger than 18 years. OBJECTIVE This study examined the feasibility of screening all patients entering the ED using the Columbia-Suicide Severity Rating Scale as well as examining the rates of suicide ideation and attempts endorsed by adolescents who present at the ED. METHODS This study used a sample of 12,113 patients between the ages of 11 and 19 years. RESULTS Results revealed that 13.5% of the participants endorsed passive suicide ideation in the month leading up to their ED visit and 11.3% of the participants reported active ideation in the prior month. Results also revealed that patients whose chief complaints were coded as psychiatric or medical trauma were more likely to endorse either active or passive suicidal ideation than other presenting problems. Patients with a psychiatric or medical trauma chief complaint were also more likely to report lifetime suicidal behavior and suicidal behavior 3 months before the ED visit. CONCLUSIONS In addition to findings, implications, feasibility, and lessons learned are discussed for other institutions or departments considering implementation of a widespread screening.Highlights:• Suicide screenings were implemented in a large pediatric emergency department.• One in 5 endorsed suicidal ideation or behavior regardless of presenting problem.• Feasibility and lessons learned are discussed for others hoping to implement a widespread screening.

BACKGROUND: Information on nurse satisfaction and unit acuity is scarce in the literature. The purpose of this study is to evaluate the effect of the MATRIX Staffing Grid (MSG) on nurse assignment satisfaction in a 20-bed inpatient rehabilitation facility. METHODS: Prospective systematic implementation study of the MSG occurred in 5 phases: development, baseline, run-in, implementation, and sustainability. Pretest/posttest nursing satisfaction data were analyzed using Wilcoxon-Mann-Whitney tests. RESULTS: Analysis of 128 satisfaction surveys demonstrated that the median total satisfaction score increased by 35% after MSG implementation (P < .05), with no change in patient satisfaction or adverse event rates. CONCLUSION: A systematic approach to implementation of the MSG evidence-based practice significantly improved nursing satisfaction with patient assignment in a way that addressed specific needs. The MSG has now been adopted into practice at our institution. The MSG may be feasible for implementation in inpatient rehabilitation units to improve staffing satisfaction.

To evaluate whether self-discontinuation of a transurethral catheter is noninferior to office discontinuation in patients requiring indwelling catheterization for postoperative urinary retention after pelvic reconstructive surgery.In this randomized noninferiority trial, patients with postoperative urinary retention after pelvic reconstructive surgery were assigned to self-discontinuation or office discontinuation of their catheter 1 week after surgery. The primary outcome was a noninferiority comparison of postoperative urinary retention at 1 week. Self-discontinuation patients were instructed on home catheter removal on postoperative day 7. Office discontinuation patients underwent a standard voiding trial on postoperative day 6-8. Postoperative urinary retention at 1 week was defined as continued catheterization on postoperative day 6-8. Secondary outcomes included urinary tract infections (UTI), residual volume at 2 weeks, duration of catheter use, recurrent postoperative urinary retention, number of patient encounters, and visual analog scales (VAS) regarding patient experience. Given a known incidence of postoperative urinary retention at 1 week (16%) and 15% noninferiority margin, a sample size of 74 per group (n=148) was planned.From January 2017 through March 2019, 217 women were screened and 157 were analyzed: 78 self-discontinuation and 79 office discontinuation. Demographic characteristics and surgeries performed were similar. Eleven patients in each group experienced postoperative urinary retention at 1 week (14.1% self-discontinuation vs 13.9% office discontinuation, P=.97), establishing noninferiority (difference 0.2%, 95% CI: -1.00, 0.10). There were significantly fewer patient encounters with self-discontinuation (42/78, 53.8% vs 79/79, 100%). Self-discontinuation patients demonstrated better VAS scores regarding pain, ease, disruption, and likelihood to use the same method again (all P.05). Though the rate of UTI was high, there was no difference between groups (59.0% self-discontinuation vs 66.7% office discontinuation, P=.32). Residual volume at 2 weeks, recurrent postoperative urinary retention, and duration of catheter use were also similar.Self-discontinuation of a transurethral catheter was noninferior to office-based discontinuation in the setting of postoperative urinary retention after pelvic reconstructive surgery. Self-discontinuation resulted in fewer patient encounters and improved patient experience.ClinicalTrials.gov, NCT02996968.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure (HF). Limited insight into underlying mechanisms has culminated in the longstanding absence of evidence-based therapies capable of mitigating the substantial morbidity and mortality associated with the syndrome. Existing clinical and epidemiological evidence suggests that excessive body fat and lipid mishandling contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are unknown. We recently developed a novel, clinically relevant, murine model of HFpEF, uncovering suppression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) signaling pathway as a critical driver of HFpEF pathogenesis. Objectives: To define and manipulate mechanisms downstream of Xbp1s in HFpEF and decipher its cardioprotective actions. Methods and Results: In the myocardium of experimental HFpEF, we detected cardiomyocyte steatosis coupled with increases in the abundance and activity of FoxO1 (Forkhead box protein O1), a conserved transcription factor involved in cell metabolism. FoxO1 depletion, as well as Xbp1s over-expression, in cardiomyocytes each ameliorated the HFpEF phenotype and reduced myocardial lipid accumulation. Strikingly, forced expression of Xbp1s in cardiomyocytes triggered proteasomal degradation of FoxO1. Furthermore, we discovered that FoxO1 is ubiquitinated upon Xbp1s over-expression, and Xbp1s-induced proteasomal degradation of FoxO1 occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-Box-containing protein 1), a protein we identified as a novel and direct transcriptional target of Xbp1s. Conclusions: Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.

Patients with ESKD undergoing hemodialysis are at high risk for cardiovascular events, which have been associated with abnormal phosphate homeostasis. Hyperphosphatemia and elevated serum fibroblast growth factor 23 (FGF23) cause vascular calcifications and left ventricular hypertrophy, respectively

The US Department of Agriculture, the US Department of Health and Human Services, and the National Kidney Foundation recommend plant-based diets, such as the Dietary Approaches to Stop Hypertension (DASH) diet, which are high in fiber; are low in saturated fat and processed meats; contain sources of

As quality improvement and patient safety come to play a larger role in health care, academic medical centers and health systems are poised to take a leadership role in addressing these issues. Academic medical centers can leverage their large integrated footprint and have the ability to innovate in this field. However, a robust quality management infrastructure is needed to support these efforts. In this context, quality and safety are often described at the executive level and at the unit level. Yet, the role of individual departments, which are often the dominant functional unit within a hospital, in realizing health system quality and safety goals has not been addressed. Developing a departmental quality management infrastructure is challenging because departments are diverse in composition, size, resources, and needs.In this article, the authors describe the model of departmental quality management infrastructure that has been implemented at the Johns Hopkins Hospital. This model leverages the fractal approach, linking departments horizontally to support peer and organizational learning and connecting departments vertically to support accountability to the hospital, health system, and board of trustees. This model also provides both structure and flexibility to meet individual departmental needs, recognizing that independence and interdependence are needed for large academic medical centers. The authors describe the structure, function, and support system for this model as well as the practical and essential steps for its implementation. They also provide examples of its early success.

Patients with known coronary artery disease presenting to the emergency department (ED) with chest pain are often admitted, yet may not be having an acute coronary syndrome (ACS).We assessed whether the use of a novel risk score and a modified thrombolysis in myocardial infarction risk score obtained in the ED could discriminate which of these high-risk patients have ACS. Chart review was performed on a cohort of 285 patients with known coronary artery disease presenting to the ED with chest pain thought to be of ischemic origin and admitted to the hospital. The ED variables were assessed with logistic regression for their association with eventual ACS diagnosis at hospital discharge. ACS was diagnosed in 74 (26%) of the patients.Non-ACS patients had a 2-day median length of stay and $6875 median inpatient (post ED) hospital charges (not including physician fees), totaling 566 hospital bed days and $1,871,250 for the 211 (74%) non-ACS patients. A novel risk score, including (1) history of prior revascularization, (2) comorbid chronic kidney disease, (3) onset of chest discomfort at rest, (4) dynamic electrocardiogram changes in the ED, (5) elevated troponin I (0.05 ng/mL) in the ED, and (6) associated illness at presentation, discriminated ACS and non-ACS with a c statistic of 0.767; the c statistic for a modified thrombolysis in myocardial infarction risk score was 0.712.Application of these risk scores may reduce the number of potentially avoidable admissions and their associated hazards and costs.

The aging hand is characterized by skin changes and soft-tissue deflation, which leads to rhytides, dermal atrophy, and distinct anatomical structures. Soft-tissue deflation and prominent hand anatomy can be corrected with volume augmentation using dermal fillers or lipofilling. Fat transfer volumizes the hand with prolonged durability and efficacy, autologous tissue replacement, and possible dermal regeneration. The senior author's (R.J.R.) technique for hand rejuvenation is described, which uses minimal access and blunt dissection to effectively augment the soft-tissue compartments of the hand. This approach addresses the prominent aged anatomy of the hand, providing excellent contour and aesthetic outcomes.

Background: Studies of neurologic deterioration in stroke have primarily focused on the acute period 24 hours after arrival. We sought to determine whether prehospital/early ED hyper-acute deterioration portends subsequent deterioration in the 24 hour acute period, as well as other prehospital factors that may predict subsequent deterioration. Methods: All subjects were enrolled in the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial. Hyper-acute neurologic deterioration was defined as Glasgow Coma Scale (GCS) decreasing ≥2 points from paramedic to ED evaluation, acute neurologic deterioration was defined as ≥4 point increase on the NIH Stroke Scale (NIHSS) from ED evaluation to 24 hours post-arrival. Other prehospital factors investigated included age, race, sex, WBC, serum glucose, arrival NIHSS, systolic blood pressure (SBP), body temperature, intracerebral hemorrhage (ICH), hypertension, smoking, diabetes, and previous stroke. Results: Of 1,643 patients, 184 (11.2%) experienced acute 24-hour deterioration. Among deteriorators; 45 % were female and mean age (SD) was 70 (±13.3) years. Median last-known-well time to assessments were: prehospital GCS 25 (IQR 15-46) mins, ED arrival GCS and NIHSS 149 (IQR 120-180) minutes and follow-up (24-hour) NIHSS 26 (IQR 18-30) hours. On multivariate analysis, hyper-acute deterioration increased the odds of subsequent acute neurological deterioration (OR = 2.24, p = 0.010, 95% CI 1.21-4.14). Other factors independently associated with acute 24-hour deterioration were ICH, arrival NIHSS, serum glucose level, SBP and body temperature (see Table 1). Conclusion: Hyper-acute deterioration is associated with increased odds of acute neurological deterioration in the subsequent 24-hour period.

Purpose To compare the intraoperative pain, anxiety, undesired movement, and cooperation between patients receiving oral diazepam or intravenous (IV) midazolam for conscious sedation during cataract surgery under topical anesthesia. Setting Ambulatory surgical center, Honolulu, Hawaii, USA. Design Prospective randomized controlled trial. Methods Patients having first-time cataract extraction with topical anesthesia were randomized to receive sedation with oral diazepam 30 minutes before surgery or IV midazolam immediately preceding surgery. The outcomes of intraoperative pain, anxiety, undesired movement, and poor cooperation were observed by the surgeon and recorded during surgery. Results One hundred fifty-six cataract surgeries were included, 83 in the IV midazolam group and 73 in the oral diazepam group. Twenty-four patients (29%) in the IV group and 7 patients (10%) in the oral group showed undesired movement ( P P > .05). Fifteen patients (18%) in the IV group and 9 patients (12%) in the oral group had anxiety ( P > .05). Three patients (4%) in the IV group and 3 patients (4%) in the oral group experienced pain ( P > .05). Conclusions Fewer patients receiving oral diazepam 30 minutes before cataract surgery than patients receiving IV midazolam immediately preceding surgery showed undesired movement during surgery. There was no statistically significant difference in the number of patients showing poor cooperation or experiencing pain or anxiety between the 2 groups. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Group beta streptococcus (GBS) is a well-documented pathogen causing serious maternal and fetal morbidity and mortality. The CDC guidelines for managing clients who test positive for GBS in pregnancy were revised and published in 2010. However, CDC and extant literature provide limited guidance on implementation strategies for these new recommendations. Although several algorithms are included in the CDC (2010) document, none combine the maternal risk factors for practical and consistent implementation from pregnancy to newborn. In response to confusion upon initial education of these guidelines, we developed an algorithm for maternal intrapartum management. In addition, we clarified the CDC (2010) newborn algorithm in response to provider request. Without altering the recommendations, both algorithms provide clarification of the CDC (2010) guidelines. The nursing process provides an organizational structure for the discussion of our efforts to translate the complex guidelines into practice. This article could provide other facilities with tools for dealing with specific aspects of the complex clinical management of perinatal GBS.

As a safety net for the health care system, quality and safety performance in emergency medicine (EM) is important for policy makers, insurers, researchers, health care providers, and patients. Developing performance indicators that are relevant, valid, feasible, and easy to measure has proven difficult. To monitor progress, patient safety should be measured objectively. Although conceptual frameworks and error taxonomies have been proposed, a practical scorecard for measuring patient safety over time in EM has been lacking. This article proposes a framework that measures safety through 4 major domains: (1) how often patients are harmed, (2) how often appropriate interventions are delivered, (3) how well errors in the system are identified and corrected, and (4) emergency department (ED) safety culture. Examples of specific measures for each of these domains are provided, but the EM community should reach consensus on what measures are important for the ED environment and patients.

A partial hospitalization program was developed for youth with moderate to severe psychiatric disorders. The objectives of this study were to prospectively assess changes from admission to discharge in the participants' clinical symptoms and psychosocial functioning, as well as the maintenance of any treatment gains at 3-month follow-up. In this naturalistic treatment study, 55 youth completed both the youth partial hospitalization program and the study. Diagnosis at admission was established by a psychiatrist based on a clinical assessment and a structured diagnostic interview. Clinician-rated and self-report measures of symptoms and psychosocial functioning were administered at admission, discharge, and follow-up to track changes over time. Clinically and statistically significant improvements were found in both symptoms and psychosocial functioning from admission to discharge on all study measures. Furthermore, these gains were maintained at 3-month follow-up. The results suggest that partial hospitalization programs can be an effective modality in treating youth with moderate to severe psychiatric disorders.

OBJECTIVES:: Due to the absence of clinical blast data, automotive injury data using the abbreviated injury score (AIS) has been extrapolated to define current North Atlantic Treaty Organisation (NATO) injury thresholds for anti-vehicle mine tests. We hypothesized that AIS, being a marker of fatality rather than disability, would be a worse predictor of poor clinical outcome compared with the lower limb-specific foot and ankle severity score (FASS). METHODS:: Using a prospectively collected trauma database, we identified UK Service Personnel sustaining lower leg injuries from under-vehicle explosions from January 2006 to December 2008. A full review of all medical documentation was performed to determine patient demographics and the severity of lower leg injury, as assessed by AIS and FASS. Clinical endpoints were defined as (1) need for amputation or (2) poor clinical outcome (defined as amputation or ongoing clinical problems). Statistical models were developed to explore the relationship between the scoring systems and clinical endpoints. RESULTS:: Sixty-three UK casualties (89 limbs) were identified with a lower limb injury after under-vehicle explosion. The mean age of the casualty was 26.0 years. At 33.6 months follow-up, 29.1% (26 of 89) required an amputation and 74.6% (67 of 89) having a poor clinical outcome. Only 9 (14%) casualties were deemed medically fit to return to full military duty. Receiver operating characteristic analysis revealed that both AIS = 2 and FASS = 4 could predict the risk of amputation, with FASS = 4 demonstrating greater specificity (43% vs. 20%) and greater positive predictive value (72% vs. 34%). In predicting poor clinical outcome, FASS was significantly superior to AIS. Probit analysis revealed that a relationship could not be developed between AIS and the probability of a poor clinical outcome. CONCLUSIONS:: Our study clearly demonstrates that AIS is not a predictor of long-term clinical outcome and that FASS would be a better quantitative measure of lower limb injury severity. Language: en

OBJECTIVE: The objective of this study was to investigate adolescent and parent attitudes toward screening adolescents for suicide risk and other mental health problems in the emergency department (ED). METHODS: Two hundred ninety-four adolescents and 300 parents completed questionnaires about the importance of screening for suicide risk and other mental health problems in the ED, what would be helpful if the screen was positive, their concerns about screening in the ED, whether they believe screening should be a routine part of an ED visit, and whether they would complete a screening during the current visit if offered the opportunity. RESULTS: Overall, parents and adolescents reported positive attitudes toward screening for suicide risk and other mental health problems in the ED, with the majority responding that it should be a routine part of ED care. Suicide risk and drug and alcohol misuse were rated as more important to screen for than any of the other mental health problems by both parents and adolescents. Adolescent females and mothers were more supportive of screening for suicide risk and mental health problems in the ED than male adolescents and fathers. Descriptive data regarding screening concerns and follow-up preferences are reported. CONCLUSIONS: Study results suggest overall positive support for screening for suicide risk and other mental health problems in the ED, with some important preferences, concerns, and parent versus adolescent and male versus female differences. Language: en

Alzheimer's disease is a progressive, neurodegenerative disorder that develops within the limbic system, spreading radially into anatomically linked brain association areas as the disease progresses. Analysis of temporal-lobe association of neocortex-derived extracellular fluid and cerebrospinal fluid from Alzheimer's disease patients shows an abundant presence of micro-RNA (miRNA), including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly sensitive LED-Northern dot-blot focusing technique, we detected the secretion of potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155 was found to induce Alzheimer-type gene expression changes in control brain cells. These included downregulation in the expression of an important repressor of the innate immune response, complement factor H (CFH). These effects were neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may provide a novel and efficacious treatment to stem the miRNA-mediated spreading of inflammatory signaling involved in Alzheimer's disease.

Lawn mower injuries in children represent an unfortunate common problem to the plastic reconstructive surgeon, which are reported approximately 68,000 per year in the United States. Compounding this problem is the fact that a standard treatment algorithm does not exist. This study follows a series of 7 pediatric patients treated for lower extremity mower injuries by a single plastic surgeon. The extent of soft tissue injury varied. All patients were treated with negative pressure wound therapy as a bridge to definitive closure. Of the 7 patients, 4 required skin grafts, 1 required primary closure, 1 underwent a lower extremity amputation secondary to wounds, and 1 was repaired using a cross-leg flap. Function limitations were minimal for all of our patients after reconstruction. Our basic treatment algorithm is presented with initial debridement followed by the simplest method possible for wound closure using negative pressure wound therapy, if necessary. Language: en

ObjectiveTo identify modifiers of age at diagnosis of Parkinson disease (PD).MethodsGenome-wide association study (GWAS) included 1,950 individuals with PD from the NeuroGenetics Research Consortium (NGRC) study. Replication was conducted in the Parkinson's, Genes and Environment study, including 209 prevalent (PAGEP) and 517 incident (PAGEI) PD cases. Cox regression was used to test association with age at diagnosis. Individuals without neurologic disease were used to rule out confounding. Gene-level analysis and functional annotation were conducted using Functional Mapping and Annotation of GWAS platform (FUMA).ResultsThe GWAS revealed 2 linked but seemingly independent association signals that mapped to LPPR1 on chromosome 9. LPPR1 was significant in gene-based analysis (p = 1E-8). The top signal (rs17763929, hazard ratio [HR] = 1.88, p = 5E-8) replicated in PAGEP (HR = 1.87, p = 0.01) but not in PAGEI. The second signal (rs73656147) was robust with no evidence of heterogeneity (HR = 1.95, p = 3E-6 in NGRC; HR = 2.14, p = 1E-3 in PAGEP + PAGEI, and HR = 2.00, p = 9E-9 in meta-analysis of NGRC + PAGEP + PAGEI). The associations were with age at diagnosis, not confounded by age in patients or in the general population. The PD-associated regions included variants with Combined Annotation Dependent Depletion (CADD) scores = 10–19 (top 1%–10% most deleterious mutations in the genome), a missense with predicted destabilizing effect on LPPR1, an expression quantitative trait locus (eQTL) for GRIN3A (false discovery rate [FDR] = 4E-4), and variants that overlap with enhancers in LPPR1 and interact with promoters of LPPR1 and 9 other brain-expressed genes (Hi-C FDR < 1E-6).ConclusionsThrough association with age at diagnosis, we uncovered LPPR1 as a modifier gene for PD. LPPR1 expression promotes neuronal regeneration after injury in animal models. Present data provide a strong foundation for mechanistic studies to test LPPR1 as a driver of response to damage and a therapeutic target for enhancing neuroregeneration and slowing disease progression.

To educate fitness and health professionals about the cardiovascular health benefits of marine-derived omega-3 fatty acids, with discussion of recommended intakes and dietary sources. To explore issues relating to higher intake of marine-derived omega-3 fatty acids, including sustainability, environmental contaminants, and cost benefits. This article describes the health benefits of marine-derived omega-3 fatty acids, with particular focus on cardiovascular disease, and discussion of recommended intakes and dietary sources. Refereed/Peer-reviewed

The effects of using a newly available water-soluble polymer bone hemostatic material in a contaminated environment were assessed in a rabbit tibial defect model. Infection rates and healing of polymer-treated bone were compared with the infection and healing of bone wax-treated bone and untreated controls after a bacterial challenge. Defects created in 24 rabbit tibias were treated with the polymer or bone wax, or left without a hemostatic agent. The defects were inoculated with Staphylococcus aureus ATCC-29213 (2.5 x 10(4) colony-forming units). After 4 weeks, all defects treated with bone wax were infected and osteomyelitis had developed, and none had evidence of bone healing. In the polymer and control groups, two defects in each group (25%) had osteomyelitis develop. The remaining six defects in each group (75%) showed no osteomyelitis and exhibited normal bone healing. The polymer-treated defects had a considerably lower rate of osteomyelitis and positive bone cultures compared with the bone wax-treated group. There were no differences between the polymer-treated and control groups in the rates of osteomyelitis, positive cultures, or bone healing. The use of a soluble polymer as an alternative to bone wax may decrease the rates of postoperative bone infections.

Alzheimer's disease is associated with progressively dysfunctional gene expression in the limbic system of the brain. The thalamus and primary visual cortex are thought to be initially spared of Alzheimer-type changes that ravage the association neocortex. In this study, using DNA arrays and Western immunoassay, gene expression patterns were examined in the thalamus and primary visual cortex of moderate-stage and late-stage Alzheimer's disease and age-matched controls using a set of proinflammatory genes known to be upregulated in the temporal lobe neocortex and hippocampus of moderate-stage Alzheimer's disease. The data indicate that, in late-stage Alzheimer's disease, proinflammatory and proapoptotic gene expression spreads into the primary visual sensory cortex. This upregulation of pathological gene expression could be, in part, responsible for the visual disturbances associated with end-stages of the Alzheimer process.

Introduction: Extracellular matrix (ECM) remodeling upon vascular stent injury contributes to both neointimal hyperplasia (restenosis) as well as endothelialization (propensity for thrombosis). Despite its important clinical implications little is known about ECM changes post stent implantation. Hypothesis: ECM remodelling, a determinant of stent healing, differs between drug-eluting (DES) and bare-metal stents (BMS). Methods: Using proteomics, we profile changes of vascular ECM proteins over time following implantation of DES and BMS in porcine coronary arteries in an overstretch model. Results: DES (n=14) or BMS (n=14) were implanted in coronary arteries of pigs. Quantitative coronary angiography and optical coherence tomography were performed at 1, 3, 7, 14 and 28 days after stent deployment. Animals were sacrificed at each of these time-points and their coronary arteries were retrieved for subsequent analysis by proteomics. A total of 126 ECM and ECM-associated proteins were identified by mass spectrometry. Within the first week after stent injury, proteins involved in inflammation and thrombosis were elevated in DES and BMS stented arteries. After one week, significant changes in regulatory ECM proteins such as small leucine rich proteins or matricellular proteins were observed. By day 28, differences between BMS and DES became apparent: basement membrane proteins as markers of cellularity were reduced in DES compared with BMS. In contrast, large aggregating proteoglycans such as aggrecan and versican were increased. Both belong to the lectican protein family that act as linkers of ECM molecules with their highly charged glycan side chains. The proteomics findings were validated by immunoblot analysis and real-time polymerase chain reaction. We were also able to detect aggrecan by immunohistochemistry in clinical specimen confirming differential expression patterns of aggrecan and versican in stented human coronary arteries. Conclusions: In the early course after BMS and DES implantation the ECM changes were similar. Significant differences were identified in the regulation of ECM proteins in long-term follow-up consisting of suppression of basement membrane proteins and up-regulation of large aggregating proteoglycans in DES.

Purpose. The human corneal oxygen uptake responses associated with the static (nonblinking) and dynamic (blinking) wear of five rigid gas-permeable materials with high oxygen permeabilities were determined for three different center thicknesses and compared with the responses for the normal open eye and severe hypoxic stress (static wear of polymethylmethacrylate). Methods. Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode during two sessions with each of 10 human subjects. Measurements were made on the right eye for the normal open eye (air) and after 5 minutes of static and dynamic wear of polymethylmethacrylate and five rigid gas-permeable contact lens materials: Fluoroperm 92 (paflufocon A, Dk = 92), Fluoroperm 151 (paflufocon D, Dk = 151), 1992 Menicon SF-P (melafocon A, Dk = 102), 1995 Menicon SF-P (melafocon A, Dk = 159), and Menicon Z (tisilfocon A, Dk = 163-250). Lenses were manufactured in three different center thicknesses (0.12, 0.16, and 0.20 mm), with all other parameters remaining constant. Repeated-measures analysis of variance was used and included lens material (five levels), blinking condition (two levels), and lens thickness (three levels) as within-subject effects. Results. Significant differences were found in corneal oxygen responses to lens material (p < 0.001) and lens thickness (p < 0.001), with lenses of lower oxygen permeability and thicker lenses being associated with higher oxygen uptake. No statistically significant differences were noted between static or dynamic wear of the lens materials (p = 0.59). Conclusions. For those very high Dk rigid lens materials studied here, moderate changes in lens thickness or material permeability may result in modest differences in corneal hypoxic relief, whereas blinking results in no significant improvement to corneal oxygenation.

Irregular menstrual cycles, acne, and hirsutism often cause women to present to a primary care setting. This article demonstrates how to take a careful history, perform a physical examination, and order the laboratory tests necessary to diagnose polycystic ovary syndrome (PCOS). Managing PCOS complaints and maintaining important health issues are also addressed, as well as when to refer to a specialist.

The endogenous natriuretic peptide system helps maintain cardiovascular homeostasis by counterbalancing the deleterious effects of renin angiotensin system activation. This study examined whether the co-administration of an ARB (valsartan: VAL) with a NEPi (AHU377: AHU) can reduce cardiorenal disease progression in the Dahl salt-sensitive (Dahl/SS) rat model of volume-dependent hypertension. Methods: Studies were conducted in conscious Dahl/SS hypertensive rats that were maintained on a high salt diet and surgically implanted with telemetry transmitters for monitoring blood pressure. Rats were treated for 6 weeks with either vehicle, VAL (30 mg/kg, PO) or VAL+AHU (30 + 30 mg/kg, PO). Changes in cardiac and renal functions were measured via Left Ventricle (LV) pressure-volume loops and biomarkers (KIM-1, NGAL and osteopontin). Results: Dahl/SS rats maintained on a high salt diet exhibited a progressive decrease in body weight gain, progressive increases in blood pressure and elevation of plasma and urinary biomarkers indicative of cardiac stress or renal injury. VAL and VAL+AHU both improved body weight gain and blunted the progressive hypertension. However, the magnitude of the antihypertensive effect was greater for VAL+AHU (peak change: - 33 ± 3 mmHg) than for VAL alone (peak change: -15 ± 5 mmHg). VAL+AHU treatment provided greater renal protective effects, based on renal biomarkers KIM-1 (286 ± 29 vs. 341 ± 59 ng), NGAL (58 ±9 vs. 108 ± 28 μg) and osteopontin (1637 ± 372 vs 2155 ± 748 ng), than VAL alone. The VAL+AHU treatment group demonstrated a greater normalization in LV function, with improved systolic contractility over VAL alone (preload-adjusted PWR max = 1 ± 0.1 vs. 2 ± 0.5 μWatt/uL). Most notably, the VAL+AHU group exhibited a greater survival rate (94%: 15 of 16) than either the VAL (75%: 12 of 16) or vehicle (70%: 14 of 20) groups. Conclusion: In summary, chronic co-administration of an ARB and NEPi to Dahl/SS rats significantly attenuated progression of hypertension, suppressed increases in biomarkers indicative of renal injury, improved cardiac function and increased overall survival. These results suggest that co-administration of an ARB and NEPi may confer a beneficial therapeutic strategy for the treatment of cardiorenal disease.

We analyzed spirometry results for 351 male hazardous materials firefighters from 1996 to 1999 who underwent one or more annual medical surveillance/fitness for duty examinations: 276 (79%) technicians and 75 (21%) support members. Support members had a very limited potential for hazardous materials exposure and served as referents. In cross-sectional comparisons, the technicians' average forced vital capacity and forced expiratory volume in 1 second were either statistically better or not significantly different from that of the support members at all four examinations. Longitudinally, no statistically significant differences were seen for forced vital capacity. The mean percent of predicted forced expiratory volume in 1 second decreased by 3% for technicians (P = 0.029), support controls (P = 0.433), and the total cohort (P = 0.014). Although respiratory irritants are the most common type of exposure in hazardous materials releases, the results suggest that hazardous materials technicians do not lose pulmonary function at a more accelerated rate than support team firefighters.

To determine the validity of transabdominal ultrasound in the detection of a two-vessel and a three-vessel umbilical cord.The ultrasound and pathology databases were collated between January 1, 1999, and December 31, 2000. Only those cases with ultrasound and pathology information concerning the number of vessels in the umbilical cord were included for analysis (group 1). In addition, 27 cases with a two-vessel umbilical cord were included from the ultrasound database before January 1, 1999, for which pathologic information was also obtained (group 2).A total of 1295 ultrasound/pathology reports were entered from January 1, 1999, through December 31, 2000; 268 cases did not have complete information, leaving 1027 for analysis (group 1). The visualization rate of the number of vessels in the umbilical cord increased from 15 to 17 weeks' gestation (74.1-97.6%; P.001). The visualization rate remained stable from 17.0 to 35.9 weeks' gestation, and then declined to 83.3% (P.01). The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of a two-vessel umbilical cord were 85%, 99.7%, 85%, and 99.7%, respectively.The detection rate of either a two-vessel or three-vessel umbilical cord is best achieved between 17 and 36 weeks' gestation. In the majority of two-vessel umbilical cords that were called three-vessel, an appropriate transverse image of the umbilical cord was not obtained.