Evidence of an excitatory purinergic innervation in mouse corpus cavernosum smooth muscle.

BACKGROUND: Evidence suggests that the corpus cavernosum smooth muscle (CCSM) cells of several species, including humans, express purinergic P2X receptors, but it is not known if the corpus cavernosum has an excitatory purinergic innervation. AIM: In this study we aimed to determine if the mouse CCSM has a functional purinergic innervation. METHODS: Mouse CCSM myocytes were enzymatically isolated and studied using the perforated patch configuration of the patch clamp technique. Isometric tension was measured in whole cavernosum tissue subjected to electrical field stimulation (EFS) to evoke nerve-mediated responses. OUTCOMES: The mouse CCSM myocytes expressed P2X1 receptors, and adenosine triphosphate (ATP) evoked inward currents in these cells. In addition, P2X1-mediated contractions were recorded in whole tissue in response to EFS. RESULTS: In cells held under a voltage clamp at -60 mV, ATP (1 µm) evoked large inward currents (mean approximately 900 pA). This current rapidly declined but was repeatable at 8-minute intervals. α,ß-methylene ATP (10 µM), an agonist of P2X1 and P2X3 receptors, caused a similar current that also rapidly declined. Desensitization to α,ß-methylene ATP negated the effect of ATP, but the ATP effect was restored 8 minutes after washout of α,ß-methylene ATP. The effect of ATP was reversibly blocked by NF449 (1 µm), a selective antagonist of P2X1 receptors. In isometric tension experiments electrical field stimulation (EFS) at 0.5-8 Hz evoked frequency-dependent contractions in the presence of l-nitro arginine (l-NO-Arg) (100 µm). When phentolamine (3 µm) and atropine (1 µm) were applied, there remained a nonadrenergic, noncholinergic component of the response to EFS, consisting mainly of a transient contraction. This was significantly reduced by NF449 (1 µm). Finally, in immunocytochemistry experiments, isolated CCSM myocytes stained positively when exposed to an antibody raised against P2X1 receptors. CLINICAL IMPLICATIONS: Previous studies have shown that P2X1 receptors in CCSM are upregulated in diabetes. These findings, taken together with the functional evidence presented here, indicate that P2X1 receptors may provide an alternative therapeutic target for treatment of erectile dysfunction in patients with diabetes, which is known to be relatively resistant to treatment with phosphodiesterase 5 inhibitors. STRENGTHS AND LIMITATIONS: Strengths of this study are the use of a combination of functional experiments (patch clamp) and immunocytochemical analyses to show expression of P2X1 receptors on CCSM myocytes while also performing functional experiments to show that stimulation these receptors results in contraction of CCSM. A limitation of this study was the use of animal rather than human tissue. CONCLUSION: This investigation provides evidence that mouse corpus cavernosum smooth muscle cells express P2X1 receptors and that these receptors are involved in mediating part of the contractile response to nerve stimulation evoked by EFS.

Terephthalate Copolyesters Based on 2,3-Butanediol and Ethylene Glycol and Their Properties.

This study explores the synthesis and performance of novel copolyesters containing 2,3-butanediol (2,3-BDO) as a biobased secondary diol. This presents an opportunity for improving their thermal properties and reducing crystallinity, while also being more sustainable. It is, however, a challenge to synthesize copolyesters of sufficient molecular weight that also have high 2,3-BDO content, due to the reduced reactivity of secondary diols compared to primary diols. Terephthalate-based polyesters were synthesized in combination with different ratios of 2,3-BDO and ethylene glycol (EG). With a 2,3-BDO to EG ratio of 28:72, an Mn of 31.5 kDa was reached with a Tg of 88 °C. The Mn dropped with increasing 2,3-BDO content to 18.1 kDa for a 2,3-BDO to EG ratio of 78:22 (Tg = 104 °C) and further to 9.8 kDa (Tg = 104 °C) for the homopolyester of 2,3-BDO and terephthalate. The water and oxygen permeability both increased significantly with increasing 2,3-BDO content and even the lowest content of 2,3-BDO (28% of total diol) performed significantly worse than PET. The incorporation of 2,3-BDO had little effect on the tensile properties of the polyesters, which were similar to PET. The results suggest that 2,3-BDO can be potentially applied for polyesters requiring higher Tg and lower crystallinity than existing materials (mainly PET).

Fermented food consumption modulates the oral microbiota.

Fermented food consumption is recommended for health and environmental purposes. While it is known to impact gut microbiota, further investigation is needed to establish connections with the oral microbiota. For this purpose, we investigated the effect of daily consumption of a model cheese containing 3 Lactic Acid Bacteria (LAB) species on the oral microbiota of rats following a 3-week diet. Cheese consumption transiently modifies the oral microbiota and leads to a transient persistence of LAB in the oral cavity of 1/3 of the animals. The origin of this variability was partly explained by an overrepresentation of salivary proteins involved in the response to oxidative stress in animals without LAB persistence. These findings highlight the significance of fermented foods in shaping the diversity of the oral microbiota. Additionally, they suggest that variations in the salivary proteome among individuals may influence the permissiveness of the oral microbiota towards exogenous microorganisms.

Is the Orthopaedic Trauma Association-Open Fracture Classification (OTA-OFC) Better than the Gustilo-Anderson Classification at Predicting Fracture-Related Infections in the Tibia?

OBJECTIVES: To investigate and compare the predictive ability of the Orthopaedic Trauma Association Open Fracture Classification (OTA-OFC) and the Gustilo-Anderson classification systems for fracture-related infections (FRI) in patients with open tibia fractures. METHODS: Design: Retrospective cohort study. SETTING: Academic trauma center. PATIENT SELECTION CRITERIA: Patients aged 16 years or older with an operatively treated open tibia fracture (OTA-OTA 41, 42, and 43) between 2010 and 2021. OUTCOME MEASURES AND COMPARISONS: The primary outcome was FRI. The OTA-OFC and the Gustilo-Anderson classifications were compared in their ability to predict FRI. RESULTS: 890 patients (mean age, 43 years [range, 17 to 96]; 75% male) with 912 open tibia fractures were included. 142 (16%) had an infection. The OTA-OFC was not significantly better at predicting FRI than the Gustilo-Anderson classification (area under the curve, 0.66 vs. 0.66; P = 0.89). The Gustilo-Anderson classification was a stronger predictor of FRI than any single OTA-OFC domain, explaining 72% of FRI variance. Only the addition of the OTA-OFC wound contamination domain to Gustilo-Anderson significantly increased the variance explained (72% vs. 84%, P = 0.04). Embedded contamination increased the risk of FRI by approximately 10% as the risk of FRI with embedded contamination was 16% for Type I or IIs, 26% for Type IIIAs, 45% for Type IIIBs, and 46% for Type IIICs. CONCLUSIONS: The more complex OTA-OFC system was not better than the Gustilo-Anderson classification system in predicting FRIs in patients with open tibia fractures. Adding embedded wound contamination to the Gustilo-Anderson classification system significantly improved its prognostic ability. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Microplastics and riverine macroinvertebrate communities in a multiple-stressor context: A mesocosm approach.

Growing use of synthetic materials has increased the number of stressors that can degrade freshwater ecosystems. Many of these stressors are relatively new and poorly understood, such as microplastics which are now ubiquitous in freshwater systems. The effects of microplastics on freshwater biota must be investigated further in order to better manage and mitigate their impacts. Our experiment provides the first empirical evaluation of stream invertebrate community dynamics in response to microplastics of different concentrations and sizes, in combination with fine sediment, a pervasive known stressor in running waters. In a 7-week streamside experiment using 64 flow-through circular mesocosms, we investigated the effects of exposure to three simulated microplastic influxes (polyethylene microspheres at four levels between 0 and 28,800 items/event) and the addition of fine sediment (to simulate a polluted stream environment). Invertebrate drift was monitored for 48 h immediately after each microplastic influx, and benthic invertebrate communities were sampled after 28 days of microplastic and sediment manipulations. Microplastic concentration, size and fine sediment all had significant factor main effects on several invertebrate drift response metrics, whereas few microplastic main effects were seen in the benthic community. However, interactive stressor effects were common in different combinations between sediment, microplastic size and concentration, suggesting multiple-stressor relationships between microplastics and fine sediment. Microplastic ingestion was witnessed in four of 12 taxa analysed: Hydrobiosidae, Deleatidium spp., Potamopyrgus antipodarum and Archichauliodes diversus. Our findings provide insights into how microplastics affect drift and benthic community dynamics of stream invertebrates in a field-realistic experimental setting and highlight areas requiring further study. These include investigations of invertebrate drift dynamics in response to other types of microplastics, the role invertebrate size may play in determining their vulnerability to microplastic pollution, and framing more microplastic research in a field-realistic multiple-stressor context.

Beliefs about COVID-19 testing and treatment: A national survey of Black and White adults.

Objectives: Knowledge, access, and use of testing and antiviral treatments is critical to managing and mitigating the continuing burden of the novel Corona Virus (COVID-19) in the United States. This study measured knowledge, attitude, behaviors, and self-reported barriers towards COVID-19 testing and outpatient anti-viral medications (OPA) treatments among Black and older individuals who face greater hospitalization and mortality from the disease. Study design: Cross-sectional structured survey. Methods: Respondents were randomly selected from an opt-in national panel in December 2022. Equal numbers of Black and White US adults over the age of 40 (n = 1037) completed the 42 item online survey. The main measures were key sociodemographic variables of respondents, race, age, political affiliation and COVID-19 attitudes, beliefs, testing behaviors, and knowledge and barriers to OPA access. Results: Overall, awareness and knowledge of COVID-19 outpatient treatments was low. Black respondents were more likely to test for COVID-19 than White respondents but less likely to know about OPA treatments. Insurance coverage was a significant factor in use of home tests. Knowledge of OPA treatments was low across groups. White respondents were more likely than Black respondents to be aware of OPA treatments (1.75, 95 % CI [1.31-2.33]) as were higher income respondents (1.13, 95 % CI [1.08-1.17]) and self-identified Liberals (1.79, 95 % CI [1.29-2.49]). Conclusions: Clinicians should know large numbers of patients may not be testing for COVID-19, nor are they aware of outpatient treatment options and may hold inaccurate beliefs about them. Developing culturally specific patient education materials are warranted to increase testing, utilization of vaccinations and OPAs.

Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra.

Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit+ interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca2+ signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca2+ indicator, GCaMP6f, driven off the endogenous promoter for Kit (Kit-GCaMP6f mice) to identify ICC-LC in situ within urethra muscles and to characterize spontaneous and nerve-evoked Ca2+ signalling. ICC-LC generated Ca2+ waves spontaneously that propagated on average 40.1 ± 0.7 µm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca2+ signalling between ICC-LC was obtained. Ca2+ events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca2+ channels (GSK-7975A). Phenylephrine increased Ca2+ event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca2+ event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.

Analysis of the diversity pipeline for the orthopedic trauma surgeon workforce in the United States.

INTRODUCTION: There is a lack of research on the state of racial, ethnic, and gender diversity in the emerging orthopedic trauma workforce. The purpose of this study was to analyze the training pathway for diverse candidates in orthopedic trauma as it relates to race, ethnicity, and sex. METHODS: Self-reported demographic data were compared among allopathic medical students, orthopedic surgery residents, orthopedic trauma fellows, and the general population in the United States (2013-2022). Race categories consisted of White, Asian, Black, and Native American/Alaskan Native (NA/AN), and Native Hawaiian/Pacific Islander (NH/PI). Ethnicity categories were Hispanic/Latino or non-Hispanic/Latino. Sex categories were male and female. Representation was calculated at each stage of accredited training. Participation-to-prevalence ratios (PPRs) quantified the equitable representation of demographic groups in the emerging orthopedic trauma workforce relative to the US population. PPR thresholds were used to classify representation as overrepresented (PPR > 1.2), equitable (PPR = 0.8-1.2), and underrepresented (PPR < 0.8). RESULTS: Relative to medical school and orthopedic surgery residency, fewer female (48.5 % vs 16.7 % vs 18.7 %, P < 0.001), Hispanic (6.1 % vs 4.5 % vs 2.6 %, P < 0.001), Black (6.9 % vs 5.0 % vs 3.1 %, P < 0.001), and Asian (24.0 % vs 14.3 % vs 12.2 %, P < 0.001) trainees existed in orthopedic trauma fellowship training. In contrast, more male (51.5 % vs 83.3 % vs 81.3 %, P < 0.001) and White (62.8 % vs 79.1 % vs 84.0 %, P < 0.001) trainees existed in orthopedic trauma fellowship relative to earlier training stages. There were zero NA/AN or NH/PI trainees in orthopedic trauma (PPR = 0). Relative to the US population, Hispanic (PPR = 0.14), Black (PPR = 0.25), and female (PPR = 0.37) trainees were underrepresented in orthopedic trauma. In contrast, Asian (PPR = 2.04), male (PPR = 1.64), and White (PPR = 1.36) trainees were overrepresented in orthopedic trauma. CONCLUSION: Women, racial, and ethnic minorities are underrepresented in the emerging orthopedic trauma workforce relative to the US population, and earlier stages of training. Targeted recruitment and guided mentorship of these groups may lead to greater interest, engagement, and diversity in orthopedic trauma.

Establishing surgical volume benchmarks for Orthopaedic Trauma Association (OTA)-accredited fellowship training.

INTRODUCTION: Case volumes of trauma centers and surgeons influence clinical outcomes following orthopaedic trauma surgery. This study quantifies surgical volume benchmarks for Orthopaedic Trauma Association (OTA)-accredited fellowship training in the United States. METHODS: This was a retrospective cross-sectional study of orthopaedic trauma fellows graduating between 2018 and 2019 to 2022-2023. Case volume percentiles were calculated across categories and variability defined as the fold-difference between 90th and 10th percentiles. Temporal trends were assessed with linear regression. RESULTS: 446 orthopaedic trauma fellows were included in this study. Mean reported case volume increased from 898 ± 245 in 2018-2019 to 974 ± 329 in 2022-2023 (P = 0.066). Mean case volume was 924 over the study period and mostly consisted of other (418 cases, 45 %), subtrochanteric/intertrochanteric femoral neck (84 cases, 9 %), open fracture debridement (72 cases, 8 %), pelvic ring disruption / fracture (55 cases, 6 %), acetabular fracture (41 cases, 4 %), tibial shaft fracture (39 cases, 4 %), and femoral shaft fracture (38 cases, 4 %) cases. Overall variability in total reported case volume was 2.0. Variability was greatest in distal radius fracture (14.8), amputation (9.5), fasciotomy (8.0), and proximal humerus repair (5.0). CONCLUSION: Graduates from OTA-accredited fellowship training perform 924 cases on average, which exceeds the current minimum requirement of 600 cases. Case volume benchmarks can assist trainees and faculty align training goals with fellowship program strengths. More research is needed to determine evidence-based case minimum requirements for core competency training in orthopaedic trauma surgery.

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

AIMS: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. METHODS AND RESULTS: ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. CONCLUSIONS: Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

Industrial Routes from Sugars and Biomass to CMF and Other 5-(Halomethyl)furfurals.

The synthesis of 5-(halomethyl)furfurals (XMFs, X=F, Cl, Br, I), including 5-(chloromethyl)furfural (CMF), 5-(bromomethyl)furfural (BMF), 5-(iodomethyl)furfural (IMF), and 5-(fluoromethyl)furfural (FMF), from biomass represents a pivotal advancement in renewable chemistry and engineering. Harnessing waste biomass as a raw material offers a sustainable alternative to fossil-based resources, mitigating environmental degradation and addressing pressing energy needs. CMF and BMF, characterized by their enhanced stability over the hydroxyl analog, 5-(hydroxymethyl)furfural (HMF), exhibit promise as renewable building blocks for scale-up and commercialization. The surge in research interest, particularly from 2010 to 2024, reflects a growing recognition of XMFs' potential as novel platform chemicals. This review highlights the evolution of XMF synthesis methods, focusing on their transformation from saccharides and lignocellulosic biomass. Mechanistic insights and experimental setups are scrutinized for industrial feasibility and scalability, shedding light on technical challenges and avenues for further research. The analysis underscores the burgeoning significance of XMFs in the transition towards sustainable chemical production, emphasizing the importance of process optimization and mechanistic understanding for commercial deployment.

Fatal cerebritis and ventriculitis secondary to tracheoesophageal prosthesis.

Tracheoesophageal puncture and voice prosthesis placement is the preferred method of voice restoration following total laryngectomy. Although this is a safe and effective means of optimizing voice, severe complications can occur. We present the case of a patient who developed cerebritis and ventriculitis secondary to a tracheoesophageal prosthesis eroding his cervical vertebrae 20 years following pharyngo-laryngo-esophagectomy. Despite optimal antimicrobial therapy, he deteriorated and succumbed to his disease. Although tracheoesophageal prostheses are a safe and effective means of voice restoration, life-threatening complications can occur. This case report highlights a rare but severe case of cervical osteomyelitis, epidural abscess, and cerebritis and ventriculitis secondary to tracheoesophageal prosthesis. Clinicians must be aware of this severe complication in postlaryngectomy patients with tracheoesophageal prostheses.

Venous thromboembolism testing practices after orthopaedic trauma: prophylaxis regimen does not influence testing patterns.

Objectives: To determine venous thromboembolism (VTE) testing patterns in an orthopaedic trauma population and to evaluate for differences in VTE surveillance by prophylaxis regimen through a secondary analysis of the ADAPT trial. Design: Prospective randomized trial. Setting: Level I trauma center. Patients: Three hundred twenty-nine adult (18 years and older) trauma patients presenting with an operative extremity fracture proximal to the metatarsals/carpals or any pelvic or acetabular fracture requiring VTE prophylaxis. Intervention: VTE imaging studies recorded within 90 days post injury. Main Outcome Measurements: Percentage of patients tested for VTE were compared between treatment groups using Fisher's exact test. Subsequently, multivariable regression was used to determine patient factors significantly associated with risk of receiving a VTE imaging study. Results: Sixty-seven patients (20.4%) had VTE tests ordered during the study period. Twenty (29.9%) of these 67 patients with ordered VTE imaging tests had a positive finding. No difference in proportion of patients tested for VTE by prophylaxis regimen (18.8% on aspirin vs. 22.0% on LMWH, P = 0.50) was observed. Factors associated with increased likelihood of VTE testing included White race (adjusted odds ratio [aOR]: 2.61, 95% CI: 1.26-5.42), increased Injury Severity Score (aOR for every 1-point increase: 1.10, 95% CI: 1.05-1.15), and lower socioeconomic status based on the Area Deprivation Index (aOR for every 10-point increase: 1.14, 95% CI: 1.00-1.30). Conclusions: VTE surveillance did not significantly differ by prophylaxis regimen. Patient demographic factors including race, injury severity, and socioeconomic status were associated with differences in VTE surveillance. Level of Evidence: Level I, Therapeutic.

TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells.

Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the human airway. This study aimed to investigate the role of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs).PBECs were obtained from individuals undergoing bronchoscopy. They were cultured in vitro and exposed to mechanical stress in the form of compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities. ATP release was measured using a luciferin-luciferase assay. Functional TRPV2 protein expression in human PBECs was investigated by confocal calcium imaging. The role of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or siRNA knockdown of TRPV2. TRPV2 protein expression in human lung tissue was also determined by immunohistochemistry.ATP release was significantly increased in PBECs subjected to CFSS compared with control (unstimulated) PBECs (N = 3, ***P < 0.001). PBECs expressed functional TRPV2 channels. TRPV2 protein was also detected in fixed human lung tissue. ATP release from FFS stimulated PBECs was decreased by the TRPV2 inhibitor tranilast (N = 3, **P < 0.01) (vehicle: 159 ± 17.49 nM, tranilast: 25.08 ± 5.1 nM) or by TRPV2 siRNA knockdown (N = 3, *P < 0.05) (vehicle: 197 ± 24.52 nM, siRNA: 119 ± 26.85 nM).In conclusion, TRPV2 is expressed in the human airway and modulates ATP release from mechanically stimulated PBECs.

Fix or Replace? Patient Preferences for the Treatment of Geriatric Lower Extremity Fractures: A Discrete Choice Experiment.

Introduction: When considering treatment options for geriatric patients with lower extremity fractures, little is known about which outcomes are prioritized by patients. This study aimed to determine the patient preferences for outcomes after a geriatric lower extremity fracture. Materials and Methods: We administered a discrete choice experiment survey to 150 patients who were at least 60 years of age and treated for a lower extremity fracture at a Level I trauma center. The discrete choice experiment presented study participants with 8 sets of hypothetical outcome comparisons, including joint preservation (yes or no), risk of reoperation at 6 months and 24 months, postoperative weightbearing status, disposition, and function as measured by return to baseline walking distance. We estimated the relative importance of these potential outcomes using multinomial logit modeling. Results: The strongest patient preference was for maintained function after treatment (59%, P < .001), followed by reoperation within 6 months (12%, P < .001). Although patients generally favored joint preservation, patients were willing to change their preference in favor of joint replacement if it increased function (walking distance) by 13% (SE, 66%). Reducing the short-term reoperation risk (12%, P < .001) was more important to patients than reducing long-term reoperation risk (4%, P = .33). Disposition and weightbearing status were lesser priorities to patients (9%, P < .001 and 7%, P < .001, respectively). Discussion: After a lower extremity fracture, geriatric patients prioritized maintained walking function. Avoiding short-term reoperation was more important than avoiding long-term reoperation. Joint preservation through fracture fixation was the preferred treatment of geriatric patients unless arthroplasty or arthrodesis provides a meaningful functional benefit. Hospital disposition and postoperative weightbearing status were less important to patients than the other included outcomes. Conclusions: Geriatric patients strongly prioritize function over other outcomes after a lower extremity fracture.

Regulation of nerve-evoked contractions of the murine vas deferens.

Stimulation of sympathetic nerves in the vas deferens yields biphasic contractions consisting of a rapid transient component resulting from activation of P2X1 receptors by ATP and a secondary sustained component mediated by activation of α1-adrenoceptors by noradrenaline. Noradrenaline can also potentiate the ATP-dependent contractions of the vas deferens, but the mechanisms underlying this effect are unclear. The purpose of the present study was to investigate the mechanisms underlying potentiation of transient contractions of the vas deferens induced by activation of α1-adrenoceptors. Contractions of the mouse vas deferens were induced by electric field stimulation (EFS). Delivery of brief (1s duration) pulses (4 Hz) yielded transient contractions that were inhibited tetrodotoxin (100 nM) and guanethidine (10 µM). α,ß-meATP (10 µM), a P2X1R desensitising agent, reduced the amplitude of these responses by 65% and prazosin (100 nM), an α1-adrenoceptor antagonist, decreased mean contraction amplitude by 69%. Stimulation of α1-adrenoceptors with phenylephrine (3 µM) enhanced EFS and ATP-induced contractions and these effects were mimicked by the phorbol ester PDBu (1 µM), which activates PKC. The PKC inhibitor GF109203X (1 µM) prevented the stimulatory effects of PDBu on ATP-induced contractions of the vas deferens but only reduced the stimulatory effects of phenylephrine by 40%. PDBu increased the amplitude of ATP-induced currents recorded from freshly isolated vas deferens myocytes and HEK-293 cells expressing human P2X1Rs by 93%. This study indicates that: (1) potentiation of ATP-evoked contractions of the mouse vas deferens by α1-adrenoceptor activation were not fully blocked by the PKC inhibitor GF109203X and (2) that the stimulatory effect of PKC on ATP-induced contractions of the vas deferens is associated with enhanced P2X1R currents in vas deferens myocytes.