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The role of molecular chaperones, such as heat shock protein 70 (Hsp70), is not typically studied as a function of biological sex, but by addressing this gap we might improve our understanding of proteinopathic disorders that predominate in one sex. Therefore, we exposed male or female primary hippocampal cultures to preformed α-synuclein fibrils in a model of early-stage Lewy pathology. We first discovered that two mechanistically distinct inhibitors of Hsp70 function increased phospho-α-synuclein(+) inclusions more robustly in male-derived neurons. Because Hsp70 is released into extracellular compartments and may restrict cell-to-cell transmission/amplification of α-synucleinopathy, we then tested the effects of low-endotoxin, exogenous Hsp70 (eHsp70) in primary hippocampal cultures. eHsp70 was taken up by and reduced α-synuclein(+) inclusions in cells of both sexes, but pharmacological suppression of Hsp70 function attenuated the inhibitory effect of eHsp70 on perinuclear inclusions only in male neurons. In 20-month-old male mice infused with α-synuclein fibrils in the olfactory bulb, daily intranasal eHsp70 delivery also reduced inclusion numbers and the time to locate buried food. eHsp70 penetrated the limbic system and spinal cord of male mice within 3 h but was cleared within 72 h. Unexpectedly, no evidence of eHsp70 uptake from nose into brain was observed in females. A trend towards higher expression of inducible Hsp70—but not constitutive Hsp70 or Hsp40—was observed in amygdala tissues from male subjects with Lewy body disorders compared to unaffected male controls, supporting the importance of this chaperone in human disease. Women expressed higher amygdalar Hsp70 levels compared to men, regardless of disease status. Together, these data provide a new link between biological sex and a key chaperone that orchestrates proteostasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01114-6.

At early disease stages, Lewy body disorders are characterized by limbic vs. brainstem α-synucleinopathy, but most preclinical studies have focused solely on the nigrostriatal pathway. Furthermore, male gender and advanced age are two major risk factors for this family of conditions, but their influence on the topographical extents of α-synucleinopathy and the degree of cell loss are uncertain. To fill these gaps, we infused α-synuclein fibrils in the olfactory bulb/anterior olfactory nucleus complex-one of the earliest and most frequently affected brain regions in Lewy body disorders-in 3-month-old female and male mice and in 11-month-old male mice. After 6 months, we observed that α-synucleinopathy did not expand significantly beyond the limbic connectome in the 9-month-old male and female mice or in the 17-month-old male mice. However, the 9-month-old male mice had developed greater α-synucleinopathy, smell impairment and cell loss than age-matched females. By 10.5 months post-infusion, fibril treatment hastened mortality in the 21.5-month-old males, but the inclusions remained centered in the limbic system in the survivors. Although fibril infusions reduced the number of cells expressing tyrosine hydroxylase in the substantia nigra of young males at 6 months post-infusion, this was not attributable to true cell death. Furthermore, mesencephalic α-synucleinopathy, if present, was centered in mesolimbic circuits (ventral tegmental area/accumbens) rather than within strict boundaries of the nigral pars compacta, which were defined here by tyrosine hydroxylase immunolabel. Nonprimate models cannot be expected to faithfully recapitulate human Lewy body disorders, but our murine model seems reasonably suited to (i) capture some aspects of Stage IIb of Lewy body disorders, which displays a heavier limbic than brainstem component compared to incipient Parkinson's disease; and (ii) leverage sex differences and the acceleration of mortality following induction of olfactory α-synucleinopathy.

A Cu-azolate metal–organic framework (MOF) uptakes stoichiometric loadings of Groups 1 and 2 metal halides, demonstrating efficient reversible release and reincorporation of immobilized anions within the framework. Ion-pairing interactions lead to anion-dependent Li+ and Mg2+ transport in Cu4(ttpm)2·0.6CuCl2, whose high surface area affords a high density of uniformly distributed mobile metal cations and halide binding sites. The ability to systematically tune the ionic conductivity yields a solid electrolyte with a Mg2+ ion conductivity rivaling the best materials reported to date. This MOF is one of the first in a promising class of frameworks that introduces the opportunity to control the identity, geometry, and distribution of the cation hopping sites, offering a versatile template for application-directed design of solid electrolytes.

Background Current postresuscitative care after cardiac arrest (CA) does not address the cause of CA. We previously reported that asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) elicit unique injury signatures. We hypothesized that the early cytokine profiles of the serum, heart, and brain differ in response to ACA versus VFCA. Methods and Results Adult male rats were subjected to 10 minutes of either ACA or VFCA. Naives and shams (anesthesia and surgery without CA) served as controls (n=12/group). Asphyxiation produced an ≈4‐minute period of progressive hypoxemia followed by a no‐flow duration of ≈6±1 minute. Ventricular fibrillation immediately induced no flow. Return of spontaneous circulation was achieved earlier after ACA compared with VFCA (42±18 versus 105±22 seconds; P Conclusions Both models of CA resulted in marked systemic, heart, and brain cytokine responses, with similar degrees of change across the 2 CA insults. Changes in cytokine levels after CA were most pronounced in the striatum compared with other brain regions. These collective observations suggest that the amplitude of the changes in cytokine levels after ACA versus VFCA may not mediate the differences in secondary injuries between these 2 CA phenotypes.

Introduction Obesity (body mass index [BMI] ≥30 kg/m^2) in men is associated with low testosterone (T) levels, and the prevalence of testosterone deficiency (TD) is greater in obese men. Information is limited regarding how BMI affects the pharmacokinetic (PK) profile or dosing of testosterone therapies (TTh) in men with TD. Serum total testosterone (TT) trough concentration (C-trough)-guided dosing achieved physiological serum TT levels (300-1100 ng/dL) in a Phase 3 trial of subcutaneous (SC) testosterone enanthate (TE) administered weekly. Objective This post-hoc analysis evaluated the association between BMI and serum TT to assess PK parameters of weekly SC TE treatment in men with TD and varying BMIs. Methods Concentration-controlled SC TE was evaluated in a single-arm Phase 3 trial. The primary endpoint was the percentage of patients who received ≥1 dose of SC TE (Safety Population) achieving an average serum TT concentration of 300-1100 ng/dL over the 7-day dosing interval, C-avg (0-168h), at Week 12. The PK Population (n=142) included all patients in the Safety Population with ≥1 blood sample drawn post-dose. Patients in the PK Population who completed the study through Week 12 (n=137) were categorized into tertiles based on baseline BMI: Tertile 1 (BMI ≤29 kg/m^2; n=45), Tertile 2 (BMI >29-32 kg/m^2; n=33), and Tertile 3 (BMI >32 kg/m^2; n=59). Assessed PK parameters included C-trough, AUC-(0-168h), C-avg (0-168h), and C-max. Weeks 6 and 12 C-trough and C-avg (0-168h) were assessed by BMI tertiles. C-trough and C-avg (0-168h) were calculated according to their Week 12 treatment doses, and an overall dose-normalized linear regression model at Week 12 was used. Results At baseline, mean (SD) serum TT levels for patients in Tertiles 1-3 were 250.7 (101.3), 235.3 (91.2), and 226.4 (81.1) ng/dL, respectively. Prior to dosing adjustments at Week 6, Tertiles 2 and 3 mean (SD) C-trough (459.2 [157.0] and 453.2 [133.0] ng/dL) were lower than Tertile 1 (616.9 [181.6] ng/dL). At Week 6, 21.2% of the total variance in C-trough levels could be predicted from BMI (P Conclusions Week 12 TT C-trough, C-avg (0-168h), and C-max were inversely related to BMI, suggesting an important role for BMI and final dose selection in SC TE exposure. Patients with higher BMI tertiles may require higher testosterone dosing to replete physiologic levels. Disclosure Yes, this is sponsored by industry/sponsor: Antares Pharma, Inc. Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma, Inc.

Background The risk of early complications is high after monoblock acetabular metal-on-metal (MoM) THA revisions. However, there is a paucity of evidence regarding clinical complications after isolated head-liner exchange of modular MoM THA. Questions/purposes The purposes of this study were (1) to describe the frequency of early complications after an isolated head-liner exchange revision of modular MoM THA; and (2) to determine whether patients who experienced complications or dislocation after head-liner exchanges had higher serum chromium (Cr) or cobalt (Co) ion levels than those who did not. Methods A review of our institution's total joint registry retrospectively identified 53 patients who underwent 54 liner exchange revisions of a modular acetabular MoM THA. The study period was from April 2008 to April 2016 at a single tertiary care center. During this period, isolated head-liner exchanges (rather than more extensive revisions) were performed in patients if they did not have evidence of loosening of the acetabular or femoral components. Reasons for revision surgery included pain, mechanical symptoms, radiographic evidence of osteolysis, elevated serum metal ions, and MRI abnormalities with 40 of the 54 hips having pain or mechanical symptoms and 38 of 54 hips having multiple reasons for revision before surgery. Patients were excluded if they did not meet the minimum postrevision followup or had the modular liner exchange secondary to infection. All revisions were from a single manufacturer with one head-liner exchange of a MoM THA from another manufacturer excluded during the study period. The mean time from index MoM THA to modular exchange was 96 (SD ± 36) months. Because the focus of this study was early complications, we had a minimum 90-day followup duration for inclusion. Mean followup after revision was 15 months (SD ± 12); a total of 56% (30 of 54) had followup of at least 12 months' duration. Complications (dislocation, infection) and reoperations were obtained by chart review performed by individuals other than the treating physician(s). Serum metal ion levels were obtained before head-liner exchange. The median serum Cr and Co levels were 6 µg/L (range, 0-76 µg/L) and 12 µg/L (range, 0-163 µg/L), respectively. Results Of the 54 revision THAs, 15 (28%) developed complications. Nine (17%) occurred within 90 days of the revision surgery and 11 (20%) resulted in reoperation. The most common complication was dislocation (12 of 54 [22%]) with recurrent dislocation noted in eight of these 12 patients. All patients with recurrent dislocation continued to dislocate and underwent repeat revision. Patients with dislocation had higher median serum Cr and Co ion levels than those without dislocation (Cr: 24 [range, 11-76] versus 4 [range, 0-70], p = 0.001 [95% confidence interval {CI}, 10-57]; Co: 41 [range, 6-163] versus 8 [range, 0-133], p = 0.016 [95% CI, 6-141]). Three (6%) of the 54 patients underwent repeat surgery for deep space infection. Conclusions Complications and reoperations are common after modular head-liner exchange in the setting of a failed MoM THA. Our study likely underestimates the frequency of complications and revisions because the followup period in this report was relatively short. Dislocation is the most common complication and elevated serum metal ion levels may be a predictor of dislocation. These findings are concerning and surgeons should be aware of the high complication risk associated with this procedure. Level of evidence Level IV, therapeutic study.

Lewy body disorders are characterized by the emergence of α-synucleinopathy in many parts of the central and peripheral nervous systems, including in the telencephalon. Dense α-synuclein+ pathology appears in regio inferior of the hippocampus in both Parkinson’s disease and dementia with Lewy bodies and may disturb cognitive function. The preformed α-synuclein fibril model of Parkinson’s disease is growing in use, given its potential for seeding the self-propagating spread of α-synucleinopathy throughout the mammalian brain. Although it is often assumed that the spread occurs through neuroanatomical connections, this is generally not examined vis-à-vis the uptake and transport of tract-tracers infused at precisely the same stereotaxic coordinates. As the neuronal connections of the hippocampus are historically well defined, we examined the first-order spread of α-synucleinopathy three months following fibril infusions centered in the mouse regio inferior (CA2 + CA3), and contrasted this to retrograde and anterograde transport of the established tract-tracers FluoroGold and biotinylated dextran amines (BDA). Massive hippocampal α-synucleinopathy was insufficient to elicit memory deficits or loss of cells and synaptic markers in this model of early disease processes. However, dense α-synuclein+ inclusions in the fascia dentata were negatively correlated with memory capacity. A modest compensatory increase in synaptophysin was evident in the stratum radiatum of cornu Ammonis in fibril-infused animals, and synaptophysin expression correlated inversely with memory function in fibril but not PBS-infused mice. No changes in synapsin I/II expression were observed. The spread of α-synucleinopathy was somewhat, but not entirely consistent with FluoroGold and BDA axonal transport, suggesting that variables other than innervation density also contribute to the materialization of α-synucleinopathy. For example, layer II entorhinal neurons of the perforant pathway exhibited somal α-synuclein+ inclusions as well as retrogradely labeled FluoroGold+ somata. However, some afferent brain regions displayed dense retrograde FluoroGold label and no α-synuclein+ inclusions (e.g. medial septum/diagonal band), supporting the selective vulnerability hypothesis. The pattern of inclusions on the contralateral side was consistent with specific spread through commissural connections (e.g. stratum pyramidale of CA3), but again, not all commissural projections exhibited α-synucleinopathy (e.g. hilar mossy cells). The topographical extent of inclusions is displayed here in high-resolution images that afford viewers a rich opportunity to dissect the potential spread of pathology through neural circuitry. Finally, the results of this expository study were leveraged to highlight the challenges and limitations of working with preformed α-synuclein fibrils.

Triphenylene ligands hexasubstituted with amino or phenol groups afford two phases of electrically conductive layered two-dimensional metal–organic frameworks upon reaction with various metals. Regardless of the identity of the metal or chelating atom, π-stacking within the MOF layers is essential to achieve high electrical conductivity, redox activity, and catalytic activity.

Introduction. Graduate professional educational programs are very rigorous and challenging, often leading to increased physiological stress and perceived anxiety for the enrolled student. Stress and anxiety levels in physical therapy students are higher than that in their age and gender matched peers. The purpose of this study was to assess the impact of an animal-assisted intervention on stress and anxiety of entry-level physical therapist (PT) students prior to a laboratory practical exam. Subjects. Twenty-three first-year PT students (mean age 23.4 ± 1.70) participated in this study. Methods. A 15-20-minute intervention which either included a therapy dog or no therapy dog was performed prior to the students’ laboratory practical exam. Following the intervention, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and state anxiety measures using the State-Trait Anxiety Inventory (STAI) were obtained. Results were compared to baseline measures as well as between each of four intervention trials using repeated measures ANOVA or Freidman test (alpha level of p 0.005). Discussion and Conclusion. The results of this study indicate that animal-assisted interventions may be beneficial in reducing perceived anxiety for students in graduate professional educational programs prior to an examination.

© 2017 American Chemical Society. Establishing catalytic structure-function relationships introduces the ability to optimize the catalyst structure for enhanced activity, selectivity, and durability against reaction conditions and prolonged catalysis. Here we present experimental and computational data elucidating the mechanism for the O2reduction reaction with a conductive nickel-based metal-organic framework (MOF). Elucidation of the O2reduction electrokinetics, understanding the role of the extended MOF structure in providing catalytic activity, observation of how the redox activity and pKaof the organic ligand influences catalysis, and identification of the catalyst active site yield a detailed O2reduction mechanism where the ligand, rather than the metal, plays a central role. More generally, familiarization with how the structural and electronic properties of the MOF influence reactivity may provide deeper insight into the mechanisms by which less structurally defined nonplatinum group metal electrocatalysts reduce O2.

Objective To examine the safety and efficacy of a high-intensity (HI) progressive rehabilitation protocol beginning 4 days after total knee arthroplasty (TKA) compared to a low-intensity (LI) rehabilitation protocol. Methods A total of 162 participants (mean ± SD ages 63 ± 7 years; 89 women) were randomized to either the HI group or LI group after TKA. Key components of the HI intervention were the use of progressive resistance exercises and a rapid progression to weight-bearing exercises and activities. Both groups were treated in an outpatient setting 2 to 3 times per week for 11 weeks (26 total sessions). Outcomes included the stair climbing test (SCT; primary outcome), timed-up-and-go (TUG) test, 6-minute walk (6MW) test, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 12-item Short Form health survey (SF-12), knee range of motion (ROM), quadriceps and hamstring strength, and quadriceps activation. Outcomes were assessed preoperatively and at 1, 2, 3 (primary end point), 6, and 12 months postoperatively. Results There were no significant differences between groups at 3 or 12 months in SCT, TUG, 6MW, WOMAC scores, knee ROM, quadriceps and hamstrings strength, quadriceps activation, or adverse event rates. By 12 months, outcomes on the 6MW, TUG, WOMAC, SF-12, quadriceps and hamstring strength, and quadriceps activation had improved beyond baseline performance in both groups. Conclusion Both the HI and LI interventions were effective in improving strength and function after TKA. HI progressive rehabilitation is safe for individuals after TKA. However, its effectiveness may be limited by arthrogenic muscular inhibition in the early postoperative period.

Despite the clear importance of the operative report in the electronic medical record, few studies have addressed the quality.We prospectively evaluated 300 consecutive patients undergoing primary total joint arthroplasties for operative report errors utilizing three different forms of documentation (standard dictation vs. templated dictation vs. a computer registry database generated operative report). The three types of reports were evaluated for errors which were classified as either major or minor.There were significantly more total errors in the standard dictation group compared to both the computer registry database generated (p0.001) and the templated operative reports (p0.001). Major errors were significantly reduced in the database generated reports compared to the templated (p0.001) and standard dictation groups (p0.001). There were significantly more minor errors in the standard dictation group (p0.001) compared to the other two groups. No statistically significant differences in major errors were noted when comparing standard vs. templated operative reports. There was no difference in minor or total errors between the database generated and templated operative reports.The use of a computer registry database generated operative report resulted in fewer major errors versus a templated or standard dictated operative report. Further research is warranted in this area to validate these findings across subspecialties and institutions.

Background Patellofemoral (PF) complications following total knee arthroplasty continue to occur. Outcomes are influenced by implant design, size and alignment in addition to patient factors. The objective of this study was to assess the effect of implant design, specifically round versus oval dome patellar components, on size selected and bony coverage in a population of 100 patients. Methods Intraoperative assessments of patella component size were performed using surgical guides for round and oval designs. Digital images of the resected patellae with and without guides were calibrated and analyzed to measure bony coverage. Lastly, the medial–lateral location of the median ridge was assessed in the native patella and compared to the positioning of the apex of the patellar implants. Results In 82% of subjects, a larger oval implant was selected compared to a round. Modest, but statistically significant, differences were observed in selected component coverage of the resected patella: 82.7% for oval versus 80.9% for round. Further, positioning of the apex of oval patellar components reproduced the median ridge of the native patella more consistently than for round components. Conclusions These findings characterized how implant design influenced size selection and coverage in a population of patients. The ability to “upsize” with oval dome components led to increases in bony coverage and better replication of the median ridge compared to round components. Quantifying the interactions between implant design, sizing and coverage for a current implant system in a population of patients supports surgical decision-making and informs the design of future implants.

Study Design Systematic review. Introduction It is accepted that the etiology of carpal tunnel syndrome (CTS) is multifactorial. One of the most commonly accepted etiologic factors for CTS is compromise of the kinematic behavior and excursion of the median nerve. Purpose of the Study The objective of this systematic review was to establish if there is a relationship between impaired median nerve excursion and CTS. Methods A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, was conducted. Studies were sought where in vivo median nerve excursion was compared between people with CTS to an appropriate control group. Quality appraisal for each study was conducted using the Newcastle-Ottawa Scale by 2 independent evaluators. Results Ten case-control studies using ultrasound imaging to quantify median nerve excursion were included. All studies were rated as of “moderate” methodologic quality having scored 6 or 7 (of 9 stars) for the Newcastle-Ottawa Scale. Seven of the 10 studies concluded that median nerve excursion was reduced in a CTS population when compared with controls. Conclusion The literature suggests that median nerve excursion is reduced in people with CTS when compared with healthy controls. Level of Evidence 3a.

A 44-year-old female presented with a chief complaint of left knee pain and dysfunction. The patient had a complex surgical history including patellar fracture repair, subsequent patellar ligament repair, and ultimately allograft reconstruction which was complicated by septic arthritis requiring graft resection. On presentation to our clinic, she was noted to have significant degenerative disease in addition to chronic extensor mechanism deficiency. She underwent primary total knee arthroplasty with concomitant tibial tubercle osteotomy and advancement. The patient has had an excellent result postoperatively including return of full range of motion without residual extensor lag.

Over 70,000 Burmese refugees have resettled in the United States in the past decade. While Burmese adolescents quickly acculturate into American society, their perspectives on health are not well-known. The purpose of this study was to identify adolescent Burmese refugee perspectives on determinants of health and health-related experiences after resettlement. In this qualitative study, Burmese adolescents took photographs depicting health-related experiences that were used as elicitation tools during focus groups. These discussions were recorded, transcribed, and analyzed for themes. Participants described positive determinants of health, including family and church. Rampant tobacco use was identified by the participants as a determinant of poor health within the Burmese community. Notably, the participants were proud to serve as liaisons within their community, despite the stressful nature of this role. Our results highlight the need to screen this population for anxiety, secondary to serving as a liaison for their community, as well as tobacco use.

Background: The medial tibial reduction osteotomy (MTRO) was introduced to achieve coronal ligamentous balance in total knee arthroplasty (TKA) patients with substantial preoperative varus deformity. Limited data exists on the outcomes of patients requiring an MTRO. This study compares outcomes of a matched cohort of patients that either required or did not require an MTRO during TKA. Methods: A retrospective review was performed on 67 patients that underwent an MTRO during primary TKA to achieve coronal balance. This patient population was matched 1:1 to another cohort of TKA patients by age, gender, and BMI that did not require an MTRO. A clinical and radiographic evaluation was utilized to compare the two cohorts. Results: Preoperatively, the tibiofemoral angle was 3.42° valgus versus 6.12° varus in the control and MTRO cohorts respectively (p=0.01). Mean postoperative tibiofemoral angles were 3.40° versus 2.43° valgus respectively. Postoperative Knee Society Scores were superior in the MTRO cohort (183.84 versus 174.58; p=0.04). Intraoperatively, no superficial MCL releases were required to achieve coronal balance in either cohort. Complications were similar and limited in both groups. Medial tibial bone resorption was observed in 64% of MTRO subjects averaging 2.02mm versus only 0.3mm in the control cohort ( p=0.01). Conclusion: Patients requiring an MTRO achieved similar alignment and superior knee scores compared to a control cohort with less varus deformity. This procedure eliminated the need for release of the superficial MCL. Resorption of medial tibial bone was commonly observed, possibly secondary to saw-induced thermal necrosis associated with performing an MTRO.

Synovial fluid aspiration is a routine practice used by most orthopaedic surgeons to aid in the diagnosis of joint infection. In patients for whom there is a low pretest probability of infection, a positive culture—particularly if it is a broth-only culture—may be considered a contaminant, especially if the bacterial species are skin pathogens. To our knowledge no study has evaluated the incidence of contamination of aspirations from the native knee. What is the frequency of false-positive cultures among knee aspirations of the native knee? Two hundred patients, with a total of 200 knees, with the diagnosis of degenerative osteoarthritis undergoing a total knee arthroplasty (TKA) were identified for this study. None of these patients had symptoms, signs, or laboratory studies to suggest the presence of joint infection; a positive culture in this population therefore would be considered contaminated. Thirty–two (16%) patients were excluded secondary to a dry aspiration. One patient was enrolled in the study but did not have the knee aspirated and another patient’s specimen was accidentally discarded. Each knee was aspirated under sterile conditions before performing the TKA. The fluid was sent for cell count and culture. If insufficient fluid was obtained for both cell count and culture, culture was performed rather than cell count. There were no false-positive cultures (zero of 166 [0%]) in aspirations of native knees. Our study would indicate that when done properly under sterile technique, cultures taken from knee arthrocentesis in patients without prosthetic joints should not be affected by perceived contaminant species. A positive specimen finding on culture should raise a strong suspicion of bacterial septic arthritis. Future studies should include more specimens as well as knees with prior TKA to help further identify the rate of false-positive cultures in knee arthrocentesis in both populations. Level I, diagnostic study.

Background: The use of a tourniquet during total knee arthroplasty (TKA) continues to be a matter of debate. Advantages of tourniquet use include improved visualization, decreased intraoperative and total blood loss, and possibly decreased transfusion requirement. However, the recent widespread adoption of antifibrinolytic therapy with tranexamic acid (TXA), may negate these benefits. The purpose of this study was to evaluate perioperative blood loss and transfusion requirement with two different tourniquet application strategies, and surgery without the use of a tourniquet during routine, primary cemented TKA.Methods: A retrospective cohort study was performed of 300 patients undergoing TKA at a single institution after the implementation of a routine intravenous TXA administration protocol and consisted of three groups based on tourniquet usage: tourniquet inflation before incision and deflation following cement hardening (TQ), tourniquet inflation prior to cement application and deflation following hardening (Partial TQ), and no tourniquet usage (No TQ). Each group consisted of 100 consecutive patients. Perioperative blood loss, change in hematocrit and transfusion requirement were compared between groups. Results: Total blood loss (estimated blood loss and drain output) was lowest in the TQ group, however this was only due a slight decrease in intraoperative estimated blood loss. There was no difference in post-operative drain output, or change in hematocrit levels from preoperative values. There were no transfusions in the Partial TQ and No TQ groups, whereas there were 5 transfusions in the TQ group.Conclusions: In the era of routine TXA administration during TKA, tourniquet usage does not appear to have a benefit in regards to perioperative blood loss or transfusion requirement.

Background α-synucleinopathy emerges quite early in olfactory structures such as the olfactory bulb and anterior olfactory nucleus (OB/AON) in Parkinson's disease. This may contribute to smell impairments years before the commencement of motor symptoms. We tested whether α-synucleinopathy can spread from the OB/AON to regions of the limbic telencephalon that harbor connections with olfactory structures. Findings α-synuclein fibrils were infused into the OB/AON. Inclusions containing pathologically phosphorylated α-synuclein (pSer129) were observed three months later in the piriform and entorhinal cortices, amygdala, and hippocampal formation. The retrograde tract-tracer FluoroGold confirmed the existence of first-order afferents at these sites. Some sites harbored FluoroGold+ neurons but no inclusions, suggestive of selective vulnerabilities. Multiple areas close to the injection site but not connected with the OB/AON remained free of inclusions, suggesting a lack of widespread uptake of fibrils from interstitial diffusion. Two independent pSer129 antibodies revealed the same labeling patterns and preadsorption control experiments confirmed a loss of pSer129 staining. Dense total α-synuclein (but not pSer129) staining was apparent in the OB/AON 1.5 h following fibril infusions, suggesting that pSer129+ staining did not reflect exogenously infused material. Waterbath sonication of fibrils for 1 h improved α-synucleinopathy transmission relative to 1 min-long probe sonication. Electron microscopy revealed that longer sonication durations reduced fibril size. The Thioflavin stain labeled cells at the infusion site and some, but not all inclusions contained ubiquitin. Three-dimensional confocal analyses revealed that many inclusions ensconced NeuN+ neuronal nuclei. Young and aged mice exhibited similar topographical spread of α-synucleinopathy. Conclusions 1) α-synucleinopathy in this model is transmitted through some, but not all neuroanatomical connections, 2) pathology is largely confined to first-order afferent sites at three months and this is most parsimoniously explained by retrograde transport, and 3) transmission in aged animals is largely similar to that in young control animals at three months post-infusion. Electronic supplementary material The online version of this article (doi:10.1186/s13024-016-0113-4) contains supplementary material, which is available to authorized users.

α-synucleinopathy emerges quite early in olfactory structures such as the olfactory bulb and anterior olfactory nucleus (OB/AON) in Parkinson's disease. This may contribute to smell impairments years before the commencement of motor symptoms. We tested whether α-synucleinopathy can spread from the OB/AON to regions of the limbic telencephalon that harbor connections with olfactory structures. α-synuclein fibrils were infused into the OB/AON. Inclusions containing pathologically phosphorylated α-synuclein (pSer129) were observed three months later in the piriform and entorhinal cortices, amygdala, and hippocampal formation. The retrograde tract-tracer FluoroGold confirmed the existence of first-order afferents at these sites. Some sites harbored FluoroGold+ neurons but no inclusions, suggestive of selective vulnerabilities. Multiple areas close to the injection site but not connected with the OB/AON remained free of inclusions, suggesting a lack of widespread uptake of fibrils from interstitial diffusion. Two independent pSer129 antibodies revealed the same labeling patterns and preadsorption control experiments confirmed a loss of pSer129 staining. Dense total α-synuclein (but not pSer129) staining was apparent in the OB/AON 1.5 h following fibril infusions, suggesting that pSer129+ staining did not reflect exogenously infused material. Waterbath sonication of fibrils for 1 h improved α-synucleinopathy transmission relative to 1 min-long probe sonication. Electron microscopy revealed that longer sonication durations reduced fibril size. The Thioflavin stain labeled cells at the infusion site and some, but not all inclusions contained ubiquitin. Three-dimensional confocal analyses revealed that many inclusions ensconced NeuN+ neuronal nuclei. Young and aged mice exhibited similar topographical spread of α-synucleinopathy. 1) α-synucleinopathy in this model is transmitted through some, but not all neuroanatomical connections, 2) pathology is largely confined to first-order afferent sites at three months and this is most parsimoniously explained by retrograde transport, and 3) transmission in aged animals is largely similar to that in young control animals at three months post-infusion.

Veterans (N=41) with type II diabetes were enrolled in a behavioral and pharmacologic intervention for cardiac risk reduction for 4 weeks at the Providence Veterans Affairs Medical Center during 2004-2007 and were followed up 3 months post intervention. Erectile dysfunction (ED) was assessed using the 5-item version of the International Index of Erectile Function (IIEF-5). Participants experienced significant improvements in hemoglobin A1c (HbA1c), diastolic blood pressure and total cholesterol levels over the course of the intervention. Change in systolic and diastolic blood pressure and reduction in or maintenance of HbA1c below 7.0% were significantly associated with change in IIEF-5 (P=0.01, P=0.01, P=0.04, respectively). These results suggest that improved blood pressure and glycemic control in men with diabetes may lead to an improvement in ED.

Control over the architectural and electronic properties of heterogeneous catalysts poses a major obstacle in the targeted design of active and stable non-platinum group metal electrocatalysts for the oxygen reduction reaction. Here we introduce Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene) as an intrinsically conductive metal-organic framework which functions as a well-defined, tunable oxygen reduction electrocatalyst in alkaline solution. Ni3(HITP)2 exhibits oxygen reduction activity competitive with the most active non-platinum group metal electrocatalysts and stability during extended polarization. The square planar Ni-N4 sites are structurally reminiscent of the highly active and widely studied non-platinum group metal electrocatalysts containing M-N4 units. Ni3(HITP)2 and analogues thereof combine the high crystallinity of metal-organic frameworks, the physical durability and electrical conductivity of graphitic materials, and the diverse yet well-controlled synthetic accessibility of molecular species. Such properties may enable the targeted synthesis and systematic optimization of oxygen reduction electrocatalysts as components of fuel cells and electrolysers for renewable energy applications., There are numerous heterogeneous oxygen reduction reaction catalysts, although synthetic tunability is rare among these materials. Here, the authors report that a conductive metal-organic framework functions as a well-defined, tunable electrocatalyst for the oxygen reduction reaction in alkaline solution.

Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon–nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation., The active site of many non-noble metal cathodic oxygen reduction catalysts consists of a nitrogen-corodinated transition metal. Here, the authors report an iron-based electrocatalyst devoid of iron–nitrogen coordination, and demonstrate its high activity in acid and alkaline media.

Purpose. To determine the predictive value of surgery-related variables for delayed inpatient functional recovery (i.e., ≥3 days to reach functional independence) after TKA.Method. 193 consecutive people undergoing TKA were included in this prospective cohort study. Inpatient functional recovery was measured daily using the Iowa Level of Assistance scale (ILAS). Two persons reviewed medical records to extract patient characteristics (i.e., age, sex, and BMI) and surgical factors (i.e., blood loss, tourniquet time, postoperative morphine use, and surgical experience). Odds ratios (OR) and area under the curves (AUC) were calculated to determine the predictive value of the putative factors and of the model on delayed functional recovery, respectively.Results. Delayed functional recovery was apparent in 76 (39%) people. Higher age, female sex, and higher BMI were all independent risk factors for delayed functional recovery (AUC (95%-CI); 0.72 (0.65–0.80)), whereas blood loss (OR (95%-CI); 1.00 (0.99–1.01)), tourniquet time (OR = 1.00 (0.98–1.02)), and postoperative morphine use (OR = 0.88 (0.37–2.06)) did not statistically improve the predictive value of the model, while surgical experience did (OR = 0.31 (0.16–0.64); AUC = 0.76 (0.69–83)).Conclusions. Surgery-related factors contribute little to the patient-related characteristics in a predictive model explaining delayed functional recovery after TKA in daily orthopaedic practice.

Assessment and treatment of benign prostatic hyperplasia, or enlarged prostate, has evolved considerably in recent years; clear evidence has accumulated for the progression of disease over time, the association between disease progression and negative outcomes, and the potential for medical management of this condition. Commensurate with the long-term preventive role of primary care, efforts can and should be made to treat the underlying condition of enlarged prostate as well as to manage the symptoms short-term. This review outlines evaluation of men presenting with lower urinary tract symptoms, examines the challenges for medical treatment and suggests how treatment choice can address these challenges.

A commercial computational fluid dynamics (CFD) code is used to compute the flow field within the first-stage rotor and stator of a two-stage mixed flow pump. The code solves the 3D Reynolds-averaged Navier-Stokes equations in rotating and stationary cylindrical coordinate systems for the rotor and stator, respectively. Turbulence effects are modeled using a standardk−εturbulence model. Stage design parameters are rotational speed890 rpm, flow coefficientφ=0.116, head coefficientψ=0.094, and specific speed2.01(5475 US). Results from the study include velocities, and static and total pressures for both the rotor and stator. Comparison is made to measured data for the rotor. The comparisons in the paper are for circumferentially averaged results and include axial and tangential velocities, static pressure, and total pressure profiles. Results of this study show that the computational results closely match the shapes and magnitudes of the measured profiles, indicating that CFD can be used to accurately predict performance.

BackgroundFatigue is one of the most commonly reported symptoms of multiple sclerosis (MS). It has a profound impact on all spheres of life, for people with MS and their relatives. It is one of the key precipitants of early retirement. Individual, group, and Internet cognitive behavioral therapy–based approaches to supporting people with MS to manage their fatigue have been shown to be effective. ObjectiveThe aim of this project was to (1) survey the types of mobile devices and level of Internet access people with MS use or would consider using for a health intervention and (2) characterize the levels of fatigue severity and their impact experienced by the people in our sample to provide an estimate of fatigue severity of people with MS in New Zealand. The ultimate goal of this work was to support the future development of a mobile intervention for the management of fatigue for people with MS. MethodsSurvey methodology using an online questionnaire was used to assess people with MS. A total of 51 people with MS participated. The average age was 48.5 years, and the large majority of the sample (77%) was female. ResultsParticipants reported significant levels of fatigue as measured with the summary score of the Neurological Fatigue Index (mean 31.4 [SD 5.3]). Most (84%) respondents scored on average more than 3 on the fatigue severity questions, reflecting significant fatigue. Mobile phone usage was high with 86% of respondents reporting having a mobile phone; apps were used by 75% of respondents. Most participants (92%) accessed the Internet from home. ConclusionsNew Zealand respondents with MS experienced high levels of both fatigue severity and fatigue impact. The majority of participants have a mobile device and access to the Internet. These findings, along with limited access to face-to-face cognitive behavioral therapy–based interventions, create an opportunity to develop a mobile technology platform for delivering a cognitive behavioral therapy–based intervention to decrease the severity and impact of fatigue in people with MS.

This paper presents the results of a study using a coarse grid to analyze the flow in the impeller of a mixed flow pump. A commercial computational fluid dynamics code (FLOTRAN) is used to solve the 3-D Reynolds Averaged Navier Stokes equations in a rotating cylindrical coordinate system. The standardk-εturbulence model is used. The mesh for this study uses 26,000 nodes and the model is run on a SPARCstation 20. This is in contrast to typical analyses using in excess of 100,000 nodes that are run on a super computer platform. The smaller mesh size has advantages in the design environment. Stage design parameters are, rotational speed 1185 rpm, flow coefficientφ=0.116, head coefficientψ=0.094, and specific speed 2.01 (5475 US). Results for the model include circumferentially averaged results at the leading and trailing edges of the impeller, and analysis of the flow field within the impeller passage. Circumferentially averaged results include axial and tangential velocities, static pressure, and total pressure. Within the impeller passage the static pressure and velocity results are presented on surfaces from the leading edge to the trailing edge, the hub to the shroud, and the pressure surface to the suction surface. Results of this study are consistent with the expected flow characteristics of mixed flow impellers, indicating that small CFD models can be used to evaluate impeller performance in the design environment.

A commercial CFD code is used to compute the flow field within the first stage impeller of a two stage axial flow pump. The code solves the 3-D Reynolds Averaged Navier Stokes equations in a rotating cylindrical coordinate system using a standardk−εturbulence model. Stage design parameters are, rotational speed 870 rpm, flow coefficientφ=0.12, head coefficientψ=0.06, and specific speed 2.86 (8070 US). Results from the study include relative and absolute velocities, flow angles, and static and total pressures. Comparison is made to measured data available for the same impeller at two planes, one upstream of the impeller and the other downstream. The comparisons are for circumferentially averaged results and include axial and tangential velocities, impeller exit flow angle, static pressure, and total pressure. Results of this study show that the computational results closely match the shapes and magnitudes of the measured profiles, indicating that CFD can be used to accurately predict performance.

The role of endothelial function testing using peripheral artery tonometry (PAT) in the evaluation of ED is not well established. Endothelial dysfunction is expected to be more common in men presenting with general or vasculogenic ED, compared with men who develop ED after prostatectomy. This study evaluated whether PAT could help identify men in whom endothelial cell dysfunction was the underlying cause of ED.A chart review of 194 men with general ED and 98 men with postprostatectomy ED was performed to abstract data on demographics, medical comorbidities, SHIM-5 scores and EndoPAT scores. Patients with preoperative ED were excluded. Statistical analysis using Student's t-test and Chi-squared analysis was performed to compare the two groups of men with respect to these variables.EndoPAT scores were not significantly different between men with general vs. postprostatectomy ED (1.97 vs. 2.08, p = 0.074). There was no relationship between EndoPAT and SHIM-5 scores in the general ED cohort. The prevalence of hypertension, hyperlipidaemia and cardiovascular (CV) disease was similar between the two groups, but diabetes and hypogonadism were more prevalent in men with general ED (21% vs. 9%, and 28% vs. 7%, p0.015). Overall, EndoPAT scores in postprostatectomy men with at least one risk factor were not significantly different compared with men with general ED with the same comorbidity, or a combination of two or more comorbidities.The value of EndoPAT testing in the clinical evaluation of ED patients is questionable.

Background Since a substantial percentage of ovarian cancers express gonadotropin receptors and are responsive to the relatively high concentrations of pituitary gonadotropins during the postmenopausal years, it has been suggested that receptor activation may contribute to the etiology and/or progression of the neoplasm. The goal of the present study was to develop a cell model to determine the impact of luteinizing hormone (LH) receptor (LHR) expression and LH-mediated LHR activation on gene expression and thus obtain insights into the mechanism of gonadotropin action on ovarian surface epithelial (OSE) carcinoma cells. Methods The human ovarian cancer cell line, SKOV-3, was stably transfected to express functional LHR and incubated with LH for various periods of time (0-20 hours). Transcriptomic profiling was performed on these cells to identify LHR expression/activation-dependent changes in gene expression levels and pathways by microarray and qRT-PCR analyses. Results Through comparative analysis on the LHR-transfected SKOV-3 cells exposed to LH, we observed the differential expression of 1,783 genes in response to LH treatment, among which five significant families were enriched, including those of growth factors, translation regulators, transporters, G-protein coupled receptors, and ligand-dependent nuclear receptors. The most highly induced early and intermediate responses were found to occupy a network impacting transcriptional regulation, cell growth, apoptosis, and multiple signaling transductions, giving indications of LH-induced apoptosis and cell growth inhibition through the significant changes in, for example, tumor necrosis factor, Jun and many others, supportive of the observed cell growth reduction in in vitro assays. However, other observations, e.g. the substantial up-regulation of the genes encoding the endothelin-1 subtype A receptor, stromal cell-derived factor 1, and insulin-like growth factor II, all of which are potential therapeutic targets, may reflect a positive mediation of ovarian cancer growth. Conclusion Overall, the present study elucidates the extensive transcriptomic changes of ovarian cancer cells in response to LH receptor activation, which provides a comprehensive and objective assessment for determining new cancer therapies and potential serum markers, of which over 100 are suggested.

Evaluation of cardiometabolic risk has become vital in primary prevention of adverse vascular events (coronary artery disease, heart attack, stroke or congestive heart failure), particularly in younger middle-aged men (40-60 years old). To discern the prevalence of events in these men, clinicians often stratify cardiovascular risk and treat according to traditional Framingham risk criteria. Yet it is evident that the traditional Framingham risk assigned to intermediate- and low-risk men will miss several of these individuals deemed at high 'cardiometabolic risk', also known as residual cardiovascular risk. This review will elaborate the definition of cardiometabolic risk and apply the use of surrogate markers for cardiovascular risk stratification in men in addition to the traditional Framingham-based markers. It will utilise both gender non-specific and gender-specific determinants of cardiometabolic risk. Lastly, it will examine minority men's health and racial differences in these determinants of cardiovascular risk. This analysis includes an electronic literature search utilising PubMed, EMBASE and MEDLINE databases to clarify the level of evidence for the stepwise utility of novel biomarkers for cardiometabolic risk in the male patient. This manuscript generates discussion of the utility of markers of cardiometabolic risk stratification. The following questions are summarised: (i) Are there non-traditional tests that might define this risk better than traditional markers? (ii) Will treatment based on this risk assessment augment present risk stratification and lower cardiovascular risk? (iii) What is known regarding racial differences surrounding cardiometabolic risk assessment? Traditional risk factors including Framingham Risk Score underestimate the overall 10 year and lifetime risk for the intermediate-risk younger middle-aged men60 years of age. This fact is especially true in the minority population. We have graded the evidence of non-gender specific and gender-specific markers of cardiometabolic risk, thereby, allowing greater clarification of risk in this population. The pragmatic use of these novel markers of cardiometabolic risk may help stratify those individuals at greater lifetime risk than that noted by the Framingham Risk Score.

Androgens not only play an important role in the development and function of the prostate but they are also intimately involved in the development and progression of prostate cancer (PCa). Within the prostate, testosterone is converted to the more potent androgen dihydrotestosterone (DHT) via the action of 5α-reductase enzymes. DHT is the primary prostatic androgen and promotes the growth and survival of normal, hyperplastic and malignant prostate tissues. Throughout the different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised, recurrent, and metastatic] there is an increase in expression of 5α-reductase enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting 5α-reductase may reduce the production of DHT in the prostate while maintaining other endogenous hormone levels. Clinical studies have shown significant PCa risk reduction by blocking this pathway with 5α-reductase inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side effects, gynaecomastia and cardiac failure. In addition, one study has shown a slight, but significant, risk of high-grade PCa. The currently available evidence does not support the routine use of 5α-reductase inhibitors to prevent PCa in the general population. It could, however, be considered as an individual option for high-risk or concerned patients with appropriate education from the prescribing provider.

High-power microwave (HPM) sources for testing systems and components at high peak powers and high energy fluences are described. Peak powers of up to 400 MW are radiated using a 150 ns, 650 kV pulse-power device to drive a class of microwave tubes termed double-anode relativistic tetrode oscillators. The DART class of devices is particularly useful for facility testing because the devices (1) provide pencil beam output at high exposure levels, (2) are fully tunable over approximately 25% bandwidth, and (3) are compatible with a wide variety of low-cost horns which provide various antenna gains. A 1 MW L-band magnetron provides power densities and energy fluences exceeding 500 W/cm/sup 2/ and 2 mJ/cm/sup 2/ for mu s pulse lengths at repetition rates to 120 Hz. The RF test environment is characterized using redundant in-situ and free-field RF diagnostics and a VAX-based data acquisition and archival system. The capability for both single-shot and repetitive testing is discussed. >

BACKGROUND To assess whether normal cardiac growth occurs after heart transplantation in the pediatric age group, we performed a study of 13 infants and children who underwent orthotopic heart transplantation at Stanford. METHODS AND RESULTS The echocardiographic data from a population of 93 normal children were analyzed to determine estimates of the fifth, 25th, 50th, 75th, and 95th percentiles of the normal pediatric population. Growth curves for each of the cardiac dimensions were stratified into six classes representing each of the percentile bands, and dimensions for the 13 patients were tracked between early postoperative (early) and point of maximal follow-up (late). Results were compared by Student's paired t test to determine whether normal growth was occurring. The mean age at transplant was 5.0 +/- 1.3 years (mean +/- SEM) (range, 0.4-12.8 years), duration of follow-up was 3.1 +/- 0.4 years (1.3-5.8 years), and change in body surface area was 0.24 +/- 0.03 m2 (0.12-0.50 m2). Both right ventricular (RV) and left ventricular (LV) chamber dimensions were within the normal range at both early and late time points and grew normally as assessed by a lack of class changes. Early wall thickness measurements were above the 95th percentile in seven of 13 patients (LV), 12 of 13 patients (septum), and four of 13 patients (RV). Wall thickness measurements remained above normal, and there were no significant class changes at late follow-up. Histological examination in five patients showed markedly increased septal myocyte width, indicating myocyte hypertrophy. Atrial and great vessel anastomotic sites showed no evidence of obstruction by Doppler and catheterization studies. CONCLUSIONS These data demonstrate that normal cardiac chamber dimensional growth occurs at greater than 3 years' follow-up after pediatric heart transplantation. Significant LV and septal (and to a lesser extent RV) hypertrophy persists and may have implications for long-term allograft growth and function.

Velocity profiles were measured in the impeller of a centrifugal pump with a two-directional laser velocimeter. Blade-to-blade profiles were measured at four circumferential positions and four radii within and one outside the four-bladed impeller. Data are presented herein at two circumferential and three radial locations. The pump was tested in two configurations; with the impeller running centered within the pump, and with the impeller orbiting with a synchronous motion (ε/r2 = 0.016). Variation in velocity profiles among the individual passages in the orbiting impeller were found. At design flow rate, these variations ranged from 30 to 60 percent for the radial component, and 15 to 25 percent for the tangential component. Tangential velocity profiles near the impeller exit (r/r2 = 0.973) were near uniform across each individual passage. Differences in the magnitude of the exit tangential velocities among the passages however, were detected. Systematic differences in the velocity profile shapes of the centered and orbiting impellers were in general not measured, the only exception being at r/r2 = 0.973 at 40 percent of the design flow rate. At this condition, two distinct radial velocity profiles were measured. Two of the impeller passages of the orbiting impeller contained a recirculation region covering 20-30 percent of the blade passage while the other two passages contained no recirculation region. The centered impeller also contained this region of reverse flow. Finally, velocity data were numerically integrated to find the forces and stiffnesses due to momentum fluxes on the impeller for the orbiting condition.

We propose a simple and practical approach to the identification, evaluation and treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a logical guide to patient management by the primary care provider (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress into a condition with profound adverse effects on quality of life. Despite the high prevalence, EP is underdiagnosed and undertreated. This situation may result from patient- and provider-related issues. Assessment of symptoms of EP should be initiated with a discussion of LUTS. Evaluation includes a focused history, physical examination and selected laboratory tests. Certain factors put the symptomatic patient at risk for disease progression; however, not all factors can be readily evaluated in the PCP setting. The serum prostate-specific antigen (PSA) level acts both as an indicator of prostatic size and a screening tool for prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan is a logical guide to patient management. Step 1, watchful waiting, is appropriate in patients with symptoms that are not bothersome. If symptoms cause bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively rapid symptom improvement. Patients with bothersome symptoms and a PSAor = 1.5 ng/ml are at risk for progression and consideration should be given to combination treatment with an AB and a 5alpha-reductase inhibitor (step 3). Patients with refractory symptoms should be referred to a urologist (step 4). Identification, evaluation and management of EP are within the domain of the primary care setting. The STEP approach provides a simple and practical framework for PCPs to manage most men with symptoms of EP.

PURPOSE Postpartum depression affects up to 22% of women who have recently given birth. Most mothers are not screened for this condition, and an ideal screening tool has not been identified. This study investigated (1) the validity of a 2-question screen and the 9-item Patient Health Questionnaire (PHQ-9) for identifying postpartum depression and (2) the feasibility of screening for postpartum depression during well-child visits. METHODS Study participants were English-literate mothers registering their 0- to 1-month-old infants for well-child visits at 7 family medicine or pediatric clinics. They were asked to complete questionnaires during well-child visits at 0 to 1, 2, 4, 6, and 9 months postpartum. Each questionnaire included 2 depression screens: the 2-question screen and the PHQ-9. The mothers also completed the depression component of the Structured Clinical Interview for DSM-IV (SCID) initially, and again at a subsequent interval if either screening result was positive for depression. RESULTS The response rate was 33%. Of the 506 women who participated, 45 (8.9%) had major depression (ie, they had a positive result on the SCID). The screen sensitivities/specificities over the course of the study were 100%/44% with the 2-question screen, 82%/84% with the PHQ-9 using simple scoring, and 67%/92% with the PHQ-9 using complex scoring. In addition, the corresponding values for the first 2 items of the PHQ-9 (ie, the 2-item Patient Health Questionnaire or PHQ-2) were 84%/79%. Some 38% of women completed their 2- to 6-month questionnaires during well-child visits; the rest completed them by mail (29%) or telephone (33%). CONCLUSIONS The 2-question screen was highly sensitive and the PHQ-9 was highly specific for identifying postpartum depression. These results suggest the value of a 2-stage procedure for screening for postpartum depression, whereby a 2-question screen that is positive for depression is followed by a PHQ-9. These screens can be easily administered in primary care clinics; feasibility of screening during well-child visits was moderate but may be better in clinics using a mass-screening approach.