Achilles tendon disorders: An overview of diagnosis and conservative treatment.

ABSTRACT: Achilles tendon-related pain affects up to 6% of the US population during their lifetime and is commonly encountered by primary care providers. An accurate diagnosis and early conservative management can improve patient quality of life and reduce unnecessary surgical consultations, saving healthcare dollars. Achilles tendon pathologies can be categorized into acute (pain lasting less than 6 weeks), chronic (pain lasting more than 6 weeks), and acute on chronic (worsening of pain with preexisting chronic Achilles tendon pathology). This article describes the diagnosis, conservative management, indications for imaging, and indications for surgical referral for acute and chronic Achilles tendon rupture, Achilles tendinitis, gastrocnemius strain, plantaris rupture, insertional Achilles tendinopathy, Haglund deformity, and noninsertional Achilles tendinopathy.

First Metatarsophalangeal Arthrodesis for Hallux Rigidus and Hallux Valgus: A Comparison of Patient Reported and Clinical Outcomes.

Few prior studies have compared the patient reported outcomes of first metatarsophalangeal arthrodesis between hallux rigidus and hallux valgus patients. Furthermore, we sought to examine the impact of postoperative radiographic hallux alignment on outcomes scores within each group. A retrospective review of 98 patients who a received primary metatarsophalangeal arthrodesis from January 2010 to March 2020. Clinical complications including nonunion were collected. Patient Reported Outcomes Measurement Information Systems (PROMIS) Physical Function, PROMIS Pain Interference, and the foot function index (FFI) revised short form scores were obtained via telephone. Patients were grouped based on review of preoperative radiographs of the foot and this grouping 37 hallux rigidus and 61 hallux valgus patients. Clinical and patient reported outcomes were compared between these pathologies. No differences in the rate of wound complications, radiographic union, and revision surgery were found between the 2 subgroups. At a median of 2.4 years (3.9 IQR) postoperatively, PROMIS and FFI scores did not vary by pathology group. For both groups, PROMIS scores were similar to the general population of the United States. The postoperative first MTP dorsiflexion angle in the hallux rigidus group was correlated with decreased FFI Pain, FFI Total, and PROMIS Pain Interference domain scores (|r| ≥ 0.40, p < .05 for all). When performing MTP arthrodesis in patients with hallux rigidus, increasing the first MTP dorsiflexion angle may correlate with improved intermediate term patient reported outcomes. However, further studies will need to be done to confirm this theoretical relationship.

A Novel Plating System for First Metatarsophalangeal Joint Arthrodesis: A Retrospective Comparison of Hybrid and Traditional Locking Plate Constructs.

BACKGROUND: Dorsal plate fixation is commonly used for first metatarsophalangeal joint (1st MTPJ) arthrodesis and plate design continues to evolve. A new staple compression plate (SCP) design attempts to utilize the continuous compression of a nitinol staple across the fusion site while simultaneously providing the stability of a dorsal locked plate. Herein, we compare the radiographic, clinical, and patient-reported outcomes of 1st MTPJ joint arthrodesis using 2 dorsal locking plate constructs including a novel SCP construct. METHODS: Forty-four patients who underwent 1st MTPJ arthrodesis between 2016 and 2020 were retrospectively evaluated. There were 2 group cohorts. Group 1 cohort included 23 patients who received a CrossRoads Extremity SCP, and Group 2 cohort included 21 patients who received a Stryker dorsal locking precontoured titanium plate (LPP). All patients were evaluated with radiographs, Patient-Reported Outcomes Measures Information System (PROMIS) outcome scores, and Foot Function Index (FFI). RESULTS: The complication and union rates did not vary between groups with a fusion rate of 95.7% in the SCP group and 90.5 % in the LPP group. Similarly, we found no significant differences in PROMIS or FFI scores between the SCP and LPP plates. CONCLUSION: Use of either dorsal locking plate construct for 1st MTPJ arthrodesis was associated with high union rates and comparable functional outcomes. As locked plate technology continues to evolve for 1st MTPJ arthrodesis, it is important that clinical outcomes are reported. LEVELS OF EVIDENCE: Level IV.

Prevalence and Risk Factors of Postoperative Falls Following Foot and Ankle Surgery.

BACKGROUND: No study has examined the incidence of risk factors for postoperative falls following foot and ankle surgery. We investigated the incidence and risk factors for postoperative falls in foot and ankle surgery using inpatient and outpatient population. METHODS: A single fellowship-trained foot and ankle surgeon instituted collection of a postoperative fall questionnaire at 2 and 6 weeks postoperatively. A retrospective review of 135 patients with complete prospectively collected fall questionnaire data was performed. Patient demographic information, injury characteristics, comorbidities, baseline medications, length of hospital stay, visual analog scale (VAS) pain scores were collected. After univariable analysis, a multivariable binary logistic regression was conducted to assess independent risk factors for postoperative falls. RESULTS: The median (interquartile range) age was 52 (21) and body mass index was 32.7 (11.1). A total of 108 patients (80%) underwent outpatient procedures. Thirty-nine of the 135 patients (28.9%) reported experiencing a fall in the first 6 weeks after surgery. In multivariable analysis, antidepressant use (adjusted odds ratio 3.41, 95% CI 1.19-9.81) and higher VAS pain scores at 2 weeks postoperatively (adjusted odds ratio 1.27, 95% CI 1.08-1.50) were found to be independent risk factors for postoperative falls. CONCLUSION: This study found a high incidence of postoperative falls in the first 6 weeks after foot and ankle surgery. Baseline antidepressant use and higher 2-week VAS pain scores were associated with postoperative falls. Foot and ankle surgeons should discuss the risk of falling with patients especially those with risk factors. LEVEL OF EVIDENCE: Level III, retrospective cohort study at a single institution.

Which surgical approach is optimal for joint preparation in talonavicular fusion - A cadaver study.

BACKGROUND: Fusion of the talonavicular joint has proven challenging in literature. The optimal surgical approach for talonavicular arthrodesis is still uncertain. This study compares the amount of physical joint preparation between dorsal and medial approaches to the talonavicular joint. METHODS: Twenty fresh frozen cadaver specimens were randomly assigned to receive either a dorsal or medial operative approach to the talonavicular joint. The joint surface was prepared, and the joint was disarticulated. Image analysis, using ImageJ, was performed by two blinded reviewers to assess the joint surface preparation and this was compared by surgical approach. RESULTS: The dorsal approach had a higher median percentage of talar and total talonavicular joint surface area prepared (75% vs. 59% (p = .007) and 82% vs. 70% (p = .005)). Irrespective of approach, the talus was significantly more difficult to prepare than the navicular (62% vs 88% (p = .001)). CONCLUSION: The dorsal approach provides superior talonavicular joint preparation. The lateral »th of the talar head was the most difficult surface to prepare, and surgeons performing double or triple arthrodesis may prepare the lateral talar head from the lateral approach. LEVEL OF EVIDENCE: Level V.

Impact of Patient Resilience on Outcomes of Open Brostrom-Gould Lateral Ligament Repair.

INTRODUCTION: Little is known about the factors affecting the intermediate outcomes of the Brostrom-Gould repair as measured by new patient-reported outcome instruments and the impact of patient resilience on postoperative outcomes. This is the first study to investigate the impact of resilience on the outcomes of lateral ligament repair. METHODS: Retrospectively, 173 patients undergoing Brostrom-Gould at single institution from January 2013 to June 2020 were identified. Patient characteristics, participation in athletic activities, surgical variables, and complications were recorded. Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference v1.1 (PI), Physical Function v1.2 (PF), and the Foot Ankle Ability Measure (FAAM) were collected. The Brief Resilience Scale was used to quantify resilience. A linear regression model was constructed to evaluate the independent effect of resilience on each PROMIS and FAAM outcome instrument. Variables were included in the regression model based on an a priori significance threshold of P <0.05 in bivariate analysis. RESULTS: Resilience's independent effect on outcome measures was as follows: PROMIS PF (unstandardized ß 8.2, 95% confidence interval [CI] 3.9 to 12.6), PROMIS PI (unstandardized ß -4.8, 95% CI -7.9 to -1.7), FAAM Activities of Daily Living (unstandardized ß 16.6, 95% CI 8.7 to 24.6), and FAAM Sports (unstandardized ß 28.4, 95% CI 15.9 to 40.9). Preoperative participation in athletic activities also had a positive independent effect on multiple outcome metrics including PROMIS PF (unstandardized ß 9.4, 95% CI 2.8 to 16.0), PROMIS PI (unstandardized ß -5.3, 95% CI -10.0 to -0.582), and FAAM Sport scores (unstandardized ß 34.4, 95% CI 15.4 to 53.4). CONCLUSIONS: Resilience and patient participation in athletic activities are independent predictors of improved postoperative functional outcomes as measured by PROMIS and FAAM instruments at intermediate term follow-up. Resilient patients and athletes reported markedly higher PF and less pain burden postoperatively. Preoperative quantification of resilience could enable improved prognostication of patients undergoing lateral ligament repair of the ankle.

First Metatarsophalangeal Joint Arthrodesis: A Narrative Review of Fixation Constructs and Their Evolution.

First metatarsophalangeal (MTP) joint arthrodesis is a surgical procedure in which the first metatarsal head is fused to the proximal phalanx of the great toe in order to permanently stiffen the first MTP joint. It was originally proposed as a treatment for severe cases of hallux valgus deformity, but the procedure's indications and utilization have expanded since its initial development. Despite a wide variety of indications, first MTP arthrodesis has been shown to have reliable, satisfactory outcomes. As a result, the development of a wide array of surgical approaches, joint preparation techniques, and fixation devices used in the procedure has occurred. In this narrative review, we highlight the evolution of fixation constructs used in first MTP arthrodesis in order to provide a frame of reference for the various types of fixation constructs available.

Diagnosis and conservative management of great toe pathologies: a review.

Acute great toe (Hallux) pain is a common complaint encountered by the primary care physician. Pathological conditions can vary from acute trauma to acute exacerbation of underlying chronic conditions. Delay in treatment or misdiagnosis can lead to debilitating loss of function and long-lasting pain. This review endeavors to discuss the pertinent history, physical exam findings, radiographic evidence, conservative treatment options, and surgical management for the musculoskeletal causes of acute and acute on chronic great toe pain in the adult population. The acute pathologies discussed in this review are hallux fractures and dislocations, turf toe, sand toe, and sesamoid disorders. The chronic pathologies discussed include hallux rigidus, hallux valgus, and chronic sesamoiditis.

Management of acute lesser toe pain.

Patients with foot pain commonly present to their primary care physicians for their initial management and treatment. These patients and their respective foot or lesser toe pain can present the physician with a complex problem with a long differential list. Depending on the timing of the pain and underlying pathology, these differentials can be divided into acute and acute exacerbation of chronic conditions. This review categorizes the history, physical exam, radiological findings, conservative treatment, and surgical management for each major cause of lesser toe pain, whether acute or chronic. The acute conditions surrounding lesser toe pain in the adult population discussed are toe fractures, toe dislocations, and metatarsal head and neck fractures. The chronic pathologies surrounding lesser toe pain in the adult population evaluated in this review include metatarsalgia, Morton's neuroma, Freiberg infraction, brachymetatarsia, bunionettes, and lesser toe disorders.

Suture Anchor-Enhanced Medial Capsulorrhaphy of the Great Toe.

The suture anchor-enhanced medial capsulorrhaphy of the great toe is utilized as an adjuvant procedure to proximal and distal osteotomies for the treatment of hallux valgus. In traditional open techniques, hallux valgus repair requires both osseous correction along with shortening of the capsule on the medial side of the metatarsophalangeal joint. Osseous correction typically corrects the intermetatarsal angle, whereas capsular correction maintains the hallux valgus angle1. Description: A standard medial approach to the 1st metatarsophalangeal joint is performed. A medial midline horizontal capsulotomy is performed starting just proximal to the medial eminence and extending distally to the base of the proximal phalanx. Once the concomitant osseous and soft-tissue procedures are completed, a vertical capsulotomy is made in the inferior capsular flap at the level of the metatarsophalangeal joint in a manner perpendicular to the first ray in order to form an L shape. A 3 to 4-mm wedge of capsule is formed near the base of the vertical limb, running obliquely to the horizontal limb, and is excised. Optionally, the free limbs of the inferior capsule are imbricated. A unicortical hole is then drilled in the first metatarsal head, and a 2.7-mm outer diameter by 7-mm deep suture anchor with 2-0 FiberWire (Arthrex) is placed. The free ends of the suture are then utilized to close the horizontal capsulotomy in a running-locking interrupted fashion. Fluoroscopic imaging is performed throughout the procedure to prevent overcorrection and varus malignment. Alternatives: Alternative treatments include L-shaped capsulorrhaphy without suture anchor augmentation, dorsolinear capsulorrhaphy, Y-shaped capsulorrhaphy, and proximal hallux osteotomy or distal hallux osteotomy without capsulorrhaphy. Rationale: Anchor-enhanced capsulorrhaphy has been proven to assist in early maintenance of hallux valgus angle correction when combined with relevant distal osteotomy techniques. The anchor-enhanced capsulorrhaphy has an advantage over traditional capsulorrhaphy methods because it allows enhanced tightening of the capsule to the bone and, therefore, the potential for enhanced short-term maintenance. Additionally, the use of a running-locking interrupted suture technique reduces the number of suture knots required for capsular closure, potentially reducing the chance of complications such as suture granuloma formation. This technique is useful in all patients with hallux valgus deformity because it helps to provide durable deformity correction through additional modification of the soft tissues surrounding the 1st metatarsophalangeal joint. Expected Outcomes: Medial capsulorrhaphy has been shown to help with short-term reduction of the hallux valgus angle, both with and without the use of suture anchors1-3. Gould et al. demonstrated the superiority of adding suture anchors to the L-shaped medial capsulorrhaphy in order to aid in prevention of early postoperative relapse of the valgus deformity in patients undergoing chevron or modified McBride osteotomy1. We have utilized this suture anchor-enhanced capsulorrhaphy technique as an adjuvant procedure in most patients receiving osteotomies or Lapidus procedures for hallux valgus correction with consistent, reproducible results. In our experience, the suture anchor-enhanced medial capsulorrhaphy is an effective and time-efficient adjunctive soft-tissue corrective procedure in hallux valgus patients. Important Tips: Always excise a small capsular wedge to start with.Throughout the capsular tightening process, utilize clinical judgment and fluoroscopy to avoid pulling the hallux into varus malalignment.If varus is noted during plication of the plantar capsule, simply undo the tightening stitch.Because the majority of capsular tightening occurs at the first distal knot during the running horizontal capsular closure, if varus is noted, untie the knot and proceed with less correction.The extra cost of the suture anchor is a drawback but should be weighed against the enhanced durability of capsular correction compared with a traditional capsulorrhaphy.Always check the position of the suture anchor under fluoroscopy before proceeding with capsular closure in order to ensure proper deployment and adequate osseous purchase.Suture anchor failure can cause misleading radiographic presentation or joint impingement. Acronyms and Abbreviations: VAS = Visual analog scaleAOFAS = American Orthopaedic Foot & Ankle SocietyHV = Hallux valgusHVA = Hallux valgus angleMTP = Metatarsophalangeal jointDVT = Deep venous thrombosis.

Molecular determinants of antiviral potency of paramyxovirus entry inhibitors.

Hendra virus (HeV) and Nipah virus (NiV) constitute the Henipavirus genus of paramyxoviruses, both fatal in humans and with the potential for subversion as agents of bioterrorism. Binding of the HeV/NiV attachment protein (G) to its receptor triggers a series of conformational changes in the fusion protein (F), ultimately leading to formation of a postfusion six-helix bundle (6HB) structure and fusion of the viral and cellular membranes. The ectodomain of paramyxovirus F proteins contains two conserved heptad repeat regions, the first (the N-terminal heptad repeat [HRN]) adjacent to the fusion peptide and the second (the C-terminal heptad repeat [HRC]) immediately preceding the transmembrane domain. Peptides derived from the HRN and HRC regions of F are proposed to inhibit fusion by preventing activated F molecules from forming the 6HB structure that is required for fusion. We previously reported that a human parainfluenza virus 3 (HPIV3) F peptide effectively inhibits infection mediated by the HeV glycoproteins in pseudotyped-HeV entry assays more effectively than the comparable HeV-derived peptide, and we now show that this peptide inhibits live-HeV and -NiV infection. HPIV3 F peptides were also effective in inhibiting HeV pseudotype virus entry in a new assay that mimics multicycle replication. This anti-HeV/NiV efficacy can be correlated with the greater potential of the HPIV3 C peptide to interact with the HeV F N peptide coiled-coil trimer, as evaluated by thermal unfolding experiments. Furthermore, replacement of a buried glutamic acid (glutamic acid 459) in the C peptide with valine enhances antiviral potency and stabilizes the 6HB conformation. Our results strongly suggest that conserved interhelical packing interactions in the F protein fusion core are important determinants of C peptide inhibitory activity and offer a strategy for the development of more-potent analogs of F peptide inhibitors.

The relationship between pedometer-determined ambulatory activity and body composition variables.

OBJECTIVE: To examine the relationship between pedometer-determined ambulatory activity (steps/day) and body composition variables body mass index (BMI) and percentage body fat). DESIGN: : Secondary analysis of a cross-sectional objective activity monitoring study for up to 21 consecutive days. SUBJECTS: A total of 109 apparently healthy adults (eight African American males, 23 African-American females, 33 Caucasian males, 45 Caucasian females), age 44.9+/-15.8 y, BMI=26.9+/-5.1 kg/m2. MEASUREMENTS: Pedometer-assessed ambulatory activity (steps/day), height and weight, and percentage body fat by bioelectrical impedance. RESULTS: Analyzed as both a continuous and a categorical variable (determined using 25th and 75th percentiles for distribution for steps/day), ambulatory activity was consistently related to body composition variables. Steps/day was inversely correlated with BMI and percentage body fat (r=-0.30, and r=-0.27, respectively, both P<0.01). The consistency of the relationship was also evident when examined using accepted BMI cut-off points for normal-weight, overweight, and obese categories. CONCLUSIONS: Individuals in this small sample with values greater than approximately 9000 steps/day are more frequently classified as normal weight for height. Individuals with values less than approximately 5000 steps/day are more frequently classified as obese. These findings require further corroborative investigation but provide preliminary cutoff points for identifying individuals at risk who may benefit from appropriate physical activity intervention.

Rhabdoviruses and the cellular ubiquitin-proteasome system: a budding interaction.

The matrix (M) proteins of vesicular stomatitis virus (VSV) and rabies virus (RV) play a key role in both assembly and budding of progeny virions. A PPPY motif (PY motif or late-budding domain) is conserved in the M proteins of VSV and RV. These PY motifs are important for virus budding and for mediating interactions with specific cellular proteins containing WW domains. The PY motif and flanking sequences of the M protein of VSV were used as bait to screen a mouse embryo cDNA library for cellular interactors. The mouse Nedd4 protein, a membrane-localized ubiquitin ligase containing multiple WW domains, was identified from this screen. Ubiquitin ligase Rsp5, the yeast homolog of Nedd4, was able to interact both physically and functionally with full-length VSV M protein in a PY-dependent manner. Indeed, the VSV M protein was multiubiquitinated by Rsp5 in an in vitro ubiquitination assay. To demonstrate further that ubiquitin may be involved in the budding process of rhabdoviruses, proteasome inhibitors (e.g., MG132) were used to decrease the level of free ubiquitin in VSV- and RV-infected cells. Viral titers measured from MG132-treated cells were reproducibly 10- to 20-fold lower than those measured from untreated control cells, suggesting that free ubiquitin is important for efficient virus budding. Last, release of a VSV PY mutant was not inhibited in the presence of MG132, signifying that the functional L domain of VSV is required for the inhibitory effect exhibited by MG132. These data suggest that the cellular ubiquitin-proteasome machinery is involved in the budding process of VSV and RV.

Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor.

Group B coxsackieviruses (CVB) utilize the coxsackievirus-adenovirus receptor (CAR) to recognize host cells. CAR is a membrane protein with two Ig-like extracellular domains (D1 and D2), a transmembrane domain and a cytoplasmic domain. The three-dimensional structure of coxsackievirus B3 (CVB3) in complex with full length human CAR and also with the D1D2 fragment of CAR were determined to approximately 22 A resolution using cryo-electron microscopy (cryo-EM). Pairs of transmembrane domains of CAR associate with each other in a detergent cloud that mimics a cellular plasma membrane. This is the first view of a virus-receptor interaction at this resolution that includes the transmembrane and cytoplasmic portion of the receptor. CAR binds with the distal end of domain D1 in the canyon of CVB3, similar to how other receptor molecules bind to entero- and rhinoviruses. The previously described interface of CAR with the adenovirus knob protein utilizes a side surface of D1.

Characterization of pseudotype VSV possessing HCV envelope proteins.

The genome of hepatitis C virus (HCV) encodes two envelope glycoproteins (E1 and E2), which are thought to be responsible for receptor binding and membrane fusion resulting in virus penetration. To investigate cell surface determinants important for HCV infection, we used a recombinant vesicular stomatitis virus (VSV) in which the glycoprotein gene was replaced with a reporter gene encoding green fluorescent protein (GFP) and produced HCV-VSV pseudotypes possessing chimeric HCV E1 or E2 glycoproteins, either individually or together. The infectivity of the pseudotypes was determined by quantifying the number of cells expressing the GFP reporter gene. Pseudotypes that contained both of the chimeric E1 and E2 proteins exhibited 10--20 times higher infectivity on HepG2 cells than the viruses possessing either of the glycoproteins individually. These results indicated that both E1 and E2 envelope proteins are required for maximal infection by HCV. The infectivity of the pseudotype virus was not neutralized by anti-VSV polyclonal antibodies. Bovine lactoferrin specifically inhibited the infection of the pseudotype virus. Treatment of HepG2 cells with Pronase, heparinase, and heparitinase but not with phospholipase C and sodium periodate reduced the infectivity. Therefore, cell surface proteins and some glycosaminoglycans play an important role in binding or entry of HCV into susceptible cells. The pseudotype VSV possessing the chimeric HCV glycoproteins might offer an efficient tool for future research on cellular receptors for HCV and for the development of prophylactics and therapeutics for hepatitis C.

N-terminal domain of Borna disease virus G (p56) protein is sufficient for virus receptor recognition and cell entry.

Borna disease virus (BDV) surface glycoprotein (GP) (p56) has a predicted molecular mass of 56 kDa. Due to extensive posttranslational glycosylation the protein migrates as a polypeptide of 84 kDa (gp84). The processing of gp84 by the cellular protease furin generates gp43, which corresponds to the C-terminal part of gp84. Both gp84 and gp43 have been implicated in viral entry involving receptor-mediated endocytosis and pH-dependent fusion. We have investigated the domains of BDV p56 involved in virus entry. For this, we used a pseudotype approach based on a recently developed recombinant vesicular stomatitis virus (VSV) in which the gene for green fluorescent protein was substituted for the VSV G protein gene (VSV Delta G*). Complementation of VSV Delta G* with BDV p56 resulted in infectious VSV Delta G* pseudotypes that contained both BDV gp84 and gp43. BDV-VSV chimeric GPs that contained the N-terminal 244 amino acids of BDV p56 and amino acids 421 to 511 of VSV G protein were efficiently incorporated into VSV Delta G* particles, and the resulting pseudotype virions were neutralized by BDV-specific antiserum. These findings indicate that the N-terminal part of BDV p56 is sufficient for receptor recognition and virus entry.

Induction of hepatic aromatase by p,p'-DDE in adult male rats.

1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE, DDE) is a stable metabolite of the pesticide DDT and a persistent environmental pollutant. Earlier reports have demonstrated that DDE is an endocrine-active compound capable of affecting early-stage sexual differentiation in male rats. Experiments based on receptor binding affinity and receptor-mediated transcriptional activation have identified DDE as an androgen receptor antagonist. Other effects of DDE include modulation of the expression and activity of cytochrome P450 (CYP) enzymes, some of which function as steroid hydroxylases, and elevation of serum estrogen levels in treated male rats. These effects suggest the possibility of DDE-caused induction of aromatase, a member of CYP family that catalyzes the conversion of C19 steroids to estrogens. The present study was conducted to determine whether hepatic aromatase was responsive to DDE treatment. We found that hepatic aromatase protein in adult male rats was greatly increased after seven daily oral treatments of DDE at a dosage of 100 mg/kg wt. per day. This induction was seen in both immunoblot and immunohistochemistry of liver tissue sections. Distribution of the aromatase in the liver corresponded to the distribution of hypertrophic hepatocytes in the tissue. Furthermore, we found a large increase in hepatic microsomal aromatase activity in DDE-treated animals, although the difference in serum 17beta-estradiol concentrations between treated animals and controls was not statistically significant. However, an in vitro experiment using primary culture of rat hepatocytes did not show a change in aromatase level after DDE treatment at four concentrations ranging from 0 to 5x10(-6) M for 24 h. Meanwhile, CYP 2B1 induction, a known DDE effect in primary rat hepatocyte culture, was seen in those cells. This study supports the notion that induction of aromatase by DDE is a contributory factor to its reproductive developmental effects.

Agreement between participant-rated and compendium-coded intensity of daily activities in a triethnic sample of women ages 40 years and older.

Participant-rated and compendium-coded intensity of daily physical activities were compared in 148 African American, 144 Native American, 51 non-Hispanic White women ages 40 to 91 years who completed 4 days of activity records. For compendium-coded intensity, reported activities were classified as light (< 3 metabolic equivalents [METS]), moderate (3-6 METS), or vigorous (> 6 METS) using the Compendium of Physical Activities (1), whereas these categories were self-assigned for participant-rated intensity. Minutes per day (min/d) spent in activities at each intensity level were computed. Relative to compendium-coded min/d, participants reported significantly greater time spent in light (+10 min/d; p < .01) and vigorous (+17 min/d; p < .001) activities, and less time spent in moderate activities (-27 min/d; p <.001). Similarly, compendium-coded estimates yielded higher rates ofparticipants meeting Centersfor Disease Control and Prevention-American College of Sports Medicine and Surgeon General recommendations than participant-rated estimates (11-18% differences) but substantially lower rates meeting American College of Sports Medicine vigorous recommendations (22% difference). Further, 247 greater kilocalories per day were estimated based on compendium-coded intensity. Kilocalories per day estimates based on compendium codings were more highly associated with pedometer counts than those based on participant ratings (p < .05). Studypatterns were generally seen across all sample subgroups. Discrepancies between participant and compendium estimates are likely to be most meaningful in studies estimating energy expenditure as it relates to health outcomes and in studies estimating vigorous activities.

Mutations in the PPPY motif of vesicular stomatitis virus matrix protein reduce virus budding by inhibiting a late step in virion release.

The N terminus of the matrix (M) protein of vesicular stomatitis virus (VSV) and of other rhabdoviruses contains a highly conserved PPPY sequence (or PY motif) similar to the late (L) domains in the Gag proteins of some retroviruses. These L domains in retroviral Gag proteins are required for efficient release of virus particles. In this report, we show that mutations in the PPPY sequence of the VSV M protein reduce virus yield by blocking a late stage in virus budding. We also observed a delay in the ability of mutant viruses to cause inhibition of host gene expression compared to wild-type (WT) VSV. The effect of PY mutations on virus budding appears to be due to a block at a stage just prior to virion release, since electron microscopic examination of PPPA mutant-infected cells showed a large number of assembled virions at the plasma membrane trapped in the process of budding. Deletion of the glycoprotein (G) in addition to these mutations further reduced the virus yield to less than 1% of WT levels, and very few particles were assembled at the cell surface. This observation suggested that G protein aids in the initial stage of budding, presumably during the formation of the bud site. Overall, our results confirm that the PPPY sequence of the VSV M protein possesses L domain activity analogous to that of the retroviral Gag proteins.

Compendium of physical activities: an update of activity codes and MET intensities.

We provide an updated version of the Compendium of Physical Activities, a coding scheme that classifies specific physical activity (PA) by rate of energy expenditure. It was developed to enhance the comparability of results across studies using self-reports of PA. The Compendium coding scheme links a five-digit code that describes physical activities by major headings (e.g., occupation, transportation, etc.) and specific activities within each major heading with its intensity, defined as the ratio of work metabolic rate to a standard resting metabolic rate (MET). Energy expenditure in MET-minutes, MET-hours, kcal, or kcal per kilogram body weight can be estimated for specific activities by type or MET intensity. Additions to the Compendium were obtained from studies describing daily PA patterns of adults and studies measuring the energy cost of specific physical activities in field settings. The updated version includes two new major headings of volunteer and religious activities, extends the number of specific activities from 477 to 605, and provides updated MET intensity levels for selected activities.