Factors in Removing Job Restrictions for Cancer Survivors in the United Kingdom Royal Air Force.

Purpose To identify personal, occupational and clinical factors associated with the lifting of restrictions on duties among Royal Air Force (RAF) personnel who have returned to work after surviving primary cancer treatment. Methods A retrospective cohort of 205 RAF personnel aged 18-58 with cancer diagnosed between 2001 and 2011 was followed-up until May 2012. Personal, occupational, and clinical information was extracted from occupational health and primary care records. Predictors of the lifting of (a) employment restrictions on UK duties at 18 months after diagnosis and (b) the lifting of all deployment restrictions at the end of the study were analysed using logistic and Cox regression models. Results At 18 months, 62% of the cancer survivors had restrictions on their UK duties lifted. The positive independent predictors of unrestricted UK duties are testicular cancer (OR 5.34; 95% CI 1.21-23.6) and no treatment being required (16.8; 1.11-255.2). The lifting of all employment restrictions and return to full deployability was achieved by 41% of the participants (median time 2.1 years), with testicular cancer (HR 2.69; 95% CI 1.38-5.26) and age at diagnosis (1.05; 1.01-1.09) being the positive independent predictors of faster lifting of all restrictions. Conclusion Diagnostic group, prognosis and type of treatment are not the only predictor of employment outcome after cancer. Patient-centred factors such as smoking, age, fatigue, job status, job type and length of employment are also important predictors of return to pre-morbid job function in cancer survivors in the RAF.

Does the informal caregiver notice HIV associated mild cognitive impairment in people living with HIV?

HIV associated minor neurocognitive disorder (MND) may be difficult to identify as key signs and symptoms (S & S) may be due to other clinical conditions. Using a self-assessment booklet "HIV and associated MND" we recruited 123 people living with HIV (PLHIV) from three sites: two hospital HIV clinics and a sexual health clinic in Sydney, Australia. Patients may down play S & S. Caregivers may notice subtle changes. By including caregivers, we aimed to find whether the caregivers noticed S & S undetected by the PLHIV. This is a sub-study of a prospective observational multi-site study aimed to validate the usefulness of a patient self-assessment tool (HIV-associated MND booklet). Using the booklet, participants and their caregivers subsequently identified S & S of MND. Sixty-four per cent (79) did not nominate a caregiver to be contacted. Participants from 2 sites 44 (36%) nominated caregivers to be contacted. Twenty-five caregivers identified more than four S & S of MND. S & S reported most by caregivers related to participants being more tired at the end of the day (76%). Participants agreed (77%). Participants also reported that they found it more difficult to remember things such as taking medications or attending medical appointments (67%). The most agreed on symptom was the requirement for increased concentration to get the same things done (Kappa P 0.599 <0.001 and McNemar 0.289). For each question at least one caregiver identified a symptom when the PLHIV did not. Caregivers were more likely than participants to report irritability and communication difficulties. It is important to include caregivers when investigating PLHIV for MND, as caregivers may validate the experience of the patient, and may also be uniquely placed to identify S & S not otherwise identified.

Predictors of return to work in cancer survivors in the Royal Air Force.

PURPOSE: Return to work (RTW) is beneficial for cancer survivors, employers and society. However, little is known about predictors of RTW in the military environment. METHODS: A cohort of 194 Royal Air Force (RAF) personnel aged 18-58 who survived primary cancer treatment between 2001 and 2011 were followed up for 18 months. Information was obtained from occupational health and primary care records. Personal, occupational and clinical predictors of RTW were identified by Cox proportional hazards regression. RESULTS: The median sickness absence before RTW was 107 days. Six months after diagnosis 54 % of participants had RTW, and reached 80 % by 12 months. Time taken to RTW was predicted by age at diagnosis, rank, trade group, pre-diagnosis sickness absence, site of cancer, treatment modality, and prognosis. RTW at 18 months were predicted by higher rank (HR = 2.31; 95 % CI 1.46-3.65), and having melanoma (9.75; 4.97-19.13). Those receiving chemotherapy were significantly less likely to have RTW compared to other treatment modalities (0.18; 0.10-0.32). CONCLUSIONS: Rank, cancer diagnostic group, and treatment modality are the most important predictors of RTW in cancer survivors in the RAF. These predictors can be used to inform rehabilitation programmes and decisions on RTW.

Postoperative Prophylactic Antibiotic Use in Breast Reduction Mammoplasty: A Single Centre Retrospective Cohort Study.

Introduction: Breast reduction mammoplasty (BRM) is a common procedure performed by plastic surgeons treating patients with hypermastia. It is customary to give preoperative prophylactic intravenous antibiotics for BRM, followed by several days of postoperative prophylactic oral antibiotics, despite the lack of evidence of their effectiveness in preventing surgical site infections (SSIs). The purpose of this study is to determine if the addition of prophylactic postoperative antibiotics is more effective in preventing SSIs in comparison to a single dose of preoperative prophylactic antibiotics in BRM. Methods: A retrospective analysis of 124 elective BRM cases by a single senior plastic surgeon was completed. Two study groups were formed based on the location of surgery and each group was assigned a different antibiotic regimen. The first antibiotic regimen consisted of a single preoperative intravenous dose of antibiotics (group 1), while the second regimen consisted of a preoperative intravenous dose followed by a 5-day course of oral antibiotics (group 2). Results: Overall SSI rate was 5.6%. Infection rate in group 1 was 8.1% in comparison to 3.2% for group 2 (P value .44). Overall, the incidence of complications was 29.0%; 38.7% in group 1 and 19.4% in group 2 (P value .03). Complications consisted of 35 cases of delayed wound healing, 7 SSIs and 2 hematomas requiring evacuation. Conclusion: Study results demonstrated that the use of postoperative prophylactic antibiotics for BRM had no significant effect on the rate of SSIs.

Introduction: La mammoplastie de réduction mammaire (MRM) est une procédure couramment pratiquée par les chirurgiens plastiques traitant des patientes ayant une hypertrophie mammaire. Il est habituel d'administrer une prophylaxie intraveineuse préopératoire pour la MRM puis plusieurs jours d'antibiothérapie prophylactique postopératoire par voie orale en dépit de l'absence de données probantes de leur efficacité à prévenir les infections du site chirurgical. L'objectif de cette étude était de déterminer si l'ajout d'antibiotiques postopératoires à visée prophylactique est plus efficace pour la prévention des infections de la cicatrice opératoire que la seule administration préopératoire d'une dose unique d'antibiotiques à visée prophylactique dans la MRM. Méthodes: Une analyse rétrospective a été réalisée par un seul chirurgien plastique expérimenté de 124 cas de MRM planifiés. Deux groupes d'étude ont été constitués en fonction du lieu de la chirurgie parmi deux centres chirurgicaux et chaque groupe ayant reçu l'un des deux protocoles d'antibiothérapie suivants : le premier schéma thérapeutique était constitué d'une seule dose préopératoire administrée par voie intraveineuse (groupe 1) et le deuxième consistait en l'administration de la dose préopératoire par voie intraveineuse suivie de 5 jours d'antibiotiques par voie orale (groupe 2). Résultats: Le taux global d'infections de la cicatrice opératoire était de 5,6%. Le taux d'infections dans le groupe 1 a été de 8,1%, comparativement à 3,2% dans le groupe 2 (P = 0,44). L'incidence globale des complications a été de 29,0%; 38,7% dans le groupe 1 et 19,4% dans le groupe 2 (P = 0,03). Les complications ont été 35 cas de retard de cicatrisation, 7 cas d'infection du site chirurgical et 2 hématomes nécessitant leur évacuation. Conclusion: Les résultats de l'étude ont montré que l'utilisation postopératoire d'antibiotiques à visée prophylactique pour la mammoplastie de réduction mammaire n'avait pas d'effet significatif sur le taux d'infections du site chirurgical.

What CPAP to use in the delivery room? Bench comparison of two methods to provide continuous positive airways pressure in neonates.

BACKGROUND: Continuous positive airway pressure (CPAP) is a recommended first-line therapy for infants with respiratory distress at birth. Resuscitation devices incorporating CPAP delivery can have significantly different imposed resistances affecting airway pressure stability and work of breathing. AIM: To compare CPAP performance of two resuscitation devices (Neopuff T-piece resuscitator and rPAP) in a neonatal lung model simulating spontaneous breathing effort at birth. METHODS: The parameters assessed were variation in delivered pressures (∆P), tidal volume (VT), inspiratory effort (model pressure respiratory muscle (PRM)) and work of breathing (WOB). Two data sequences were required with Neopuff and one with rPAP: (1) set PRM with changes in VT and (2) constant VT (preterm 6 mL, term 22 mL) with increased effort. Data were collected at CPAP settings of 5, 7 and 9 cmH2O using a 1 kg preterm (Compliance: 0.5 mL/cmH2O) and 3.5 kg term (1.0 mL/cmH2O) model. RESULTS: 2298 breaths were analysed (760 rPAP, 795 Neopuff constant VT, 743 Neopuff constant PRM). With CPAP at 9 cmH2O and set VT the mean ∆P (cmH2O) rPAP vs Neopuff 1.1 vs 5.6 (preterm) and 1.9 vs 13.4 (term), WOB (mJ) 4.6 vs 6.1 (preterm) and 35.3 vs 44.5 (term), and with set PRM mean VT (ml) decreased to 6.2 vs 5.2 (preterm) and 22.3 vs 17.5 (term) p<0.001. Similar results were found at pressures of 5 and 7 cmH2O. CONCLUSION: rPAP had smaller pressure swings than Neopuff at all CPAP levels and was thus more pressure stable. WOB was higher with Neopuff when VT was held constant. VT reduced with Neopuff when respiratory effort was constant.

Cosmetic surgery training in Canadian plastic surgery residencies: are we training competent surgeons?

BACKGROUND: With the demand for cosmetic surgery continuing to rise, it is necessary to reevaluate the current state of cosmetic surgery training during plastic surgery residency. An evaluation of cosmetic surgery training in US plastic surgery residency programs in 2006 identified several areas for improvement, resulting in changes to both the duration and content of training. OBJECTIVES: The authors assess the current state of cosmetic surgery training in Canadian plastic surgery residency programs. METHODS: A paper survey of all graduating Canadian plastic surgery residents eligible to complete the 2009 Royal College of Physicians and Surgeons of Canada fellowship examinations was performed (N = 29). The survey was conducted primarily at the Canadian Plastic Surgery Review Course in February 2009, with surveys collected from absent residents by e-mail within 1 month after the course. The survey covered 2 broad areas: (1) specifics regarding resident cosmetic surgery training and (2) confidence and satisfaction associated with this experience. RESULTS: Of the 29 residents surveyed, 28 responded (96%). The majority of Canadian plastic surgery residency programs (75%) have a designated cosmetic surgery rotation, but 90% of respondents felt it has become increasingly difficult to gain exposure to cosmetic procedures as most are performed at private surgery centers. Elective rotations at cosmetic surgery practices and resident cosmetic clinics were considered the most beneficial for cosmetic surgery education. Residents considered cosmetic surgery procedures of the face (such as rhinoplasty and facelift) more challenging, but they had more confidence with breast and body contouring procedures. CONCLUSIONS: Canadian plastic surgery residency programs need to ensure that residents continue to receive comprehensive exposure to both surgical and nonsurgical cosmetic procedures to ensure our specialty's continued leadership in this evolving and highly competitive field. A multidimensional approach utilizing a variety of readily available resources will ensure that the current and future cosmetic surgery educational needs of Canadian plastic surgery residents are met.

One-person versus two-person mask ventilation in preterm infants at birth: a pilot randomised controlled trial.

BACKGROUND: Mask leak and airway obstruction are common with mask ventilation in newborn infants, leading to suboptimal ventilation. We aimed to perform a pilot study measuring respiratory mechanics during one-person and two-person mask ventilation in preterm infants at birth. METHODS: Infants less than 30 weeks' gestation were eligible for the study. In the two-person method, one person holds the mask in place and the other provides positive pressure ventilation compared with the standard one-person mask hold. A respiratory function monitor was used in line with a T-piece resuscitator to measure mask leak and airway obstruction. Deferred consent was obtained. RESULTS: Twenty-five infants were recruited. The mean (SD) birth weight was 920.4 g (188.3), and mean (SD) gestational age was 27.3 weeks (3.0). Percentage mask leak was higher in the one-person mask method (26.4±18.5) compared with the two-person mask method (17.6±9.3) (p=0.018). The mean (SD) expired tidal volume (VTe, mL) in breaths with leak was 3.9 (1.57) in the one-person method compared with 3.05 (1.0) the two-person method (p=0.31). A significantly lower mean (SD) end-tidal carbon dioxide (EtCO2, mm Hg) was measured at 25.3 (9.9) in breaths with mask leak, compared with 30.8 (12.1) in breaths without leak. The breaths with airway obstruction had lower mean EtCO2 (25.9 vs 30.8, p=0.003) and lower mean VTe (1.71 vs 6.95, p<0.001). CONCLUSION: Mask leak and airway obstruction are common in resuscitation of preterm infants at birth. The use of the two-person mask technique is effective and it could be a useful option if mask ventilation with the one-person method is not effective. TRIAL REGISTRATION NUMBER: ACTRN12614000245695.

Time-resolved small-angle X-ray scattering studies of polymer-silica nanocomposite particles: initial formation and subsequent silica redistribution.

Small angle X-ray scattering (SAXS) is a powerful characterization technique for the analysis of polymer-silica nanocomposite particles due to their relatively narrow particle size distributions and high electron density contrast between the polymer core and the silica shell. Time-resolved SAXS is used to follow the kinetics of both nanocomposite particle formation (via silica nanoparticle adsorption onto sterically stabilized poly(2-vinylpyridine) (P2VP) latex in dilute aqueous solution) and also the spontaneous redistribution of silica that occurs when such P2VP-silica nanocomposite particles are challenged by the addition of sterically stabilized P2VP latex. Silica adsorption is complete within a few seconds at 20 °C and the rate of adsorption strongly dependent on the extent of silica surface coverage. Similar very short time scales for silica redistribution are consistent with facile silica exchange occurring as a result of rapid interparticle collisions due to Brownian motion; this interpretation is consistent with a zeroth-order Smoluchowski-type calculation.

Morphologic Analysis of the Carpal Tunnel and Median Nerve Following Open and Endoscopic Carpal Tunnel Release.

Background: Endoscopic carpal tunnel release (ECTR) has purported advantages over open release such as reduced intraoperative dissection and trauma and more rapid recovery. Endoscopic carpal tunnel release has been shown to have comparable outcomes to open release, but open release is considered easier and safer to perform. Previous studies have demonstrated an increase in carpal tunnel volume, regardless of the technique used. However, the mechanism by which this volumetric increase occurs has been debated. Our study will determine through magnetic resonance imaging (MRI) analysis the morphologic changes that occur in both open carpal tunnel release (OCTR) and ECTR, thereby clarifying any morphologic differences that occur as a result of the 2 operative techniques. We hypothesize that there will be no morphologic differences between the 2 techniques. Methods: This was a prospective study to compare the postoperative anatomy of both techniques with MRI. Nineteen patients with clinical and nerve conduction study-confirmed carpal tunnel syndrome underwent either open or endoscopic release. Magnetic resonance imaging was performed preoperatively and 6 months postoperatively in all patients to examine the volume of the carpal tunnel, transverse distance, anteroposterior (AP) distance, divergence of tendons, and Guyon's canal transverse and AP distance. Results: There was no significant difference in the postoperative morphology of the carpal tunnel and median nerve between OCTR and ECTR at 6-month follow-up on MRI. Conclusion: We conclude that there are no morphologic differences in OCTR and ECTR. It is an increase in the AP dimension that appears to be responsible for the increase in the volume of the carpal tunnel.

T-piece resuscitators: can they provide safe ventilation in a low compliant newborn lung?

BACKGROUND: T-piece resuscitators (TPRs) are used for primary newborn resuscitation in birthing and emergency rooms worldwide. A recent study has shown spikes in peak inflation pressure (PIP) over set values with two brands of TPRs inbuilt into infant warmer/resuscitation platforms. We aimed to compare delivered ventilation between two TPR drivers with inflation pressure spikes to a standard handheld TPR in a low test lung compliance (Crs), leak-free bench test model. METHODS: A single operator provided positive pressure ventilation to a low compliance test lung model (Crs 0.2-1 mL/cmH2O) at set PIP of 15, 25, 35 and 40 cmH2O. Two TPR devices with known spikes (Draeger Resuscitaire, GE Panda) were compared with handheld Neopuff (NP). Recommended settings for positive end-expiratory pressure (5 cmH2O), inflation rate of 60/min and gas flow rate 10 L/min were used. RESULTS: 2293 inflations were analysed. Draeger and GE TPR drivers delivered higher mean PIP (Panda 18.9-49.5 cmH2O; Draeger 21.2-49.2 cmH2O and NP 14.8-39.9 cmH2O) compared with set PIP and tidal volumes (TVs) compared with the NP (Panda 2.9-7.8 mL; Draeger 3.8-8.1 mL; compared with NP 2.2-6.0 mL), outside the prespecified acceptable range (±10% of set PIP and ±10% TV compared with NP). CONCLUSION: The observed spike in PIP over set values with Draeger and GE Panda systems resulted in significantly higher delivered volumes compared with the NP with identical settings. Manufacturers need to address these differences. The effect on patient outcomes is unknown.

Unexpected facile redistribution of adsorbed silica nanoparticles between latexes.

Addition of excess sterically stabilized P2VP latex to a colloidal dispersion of P2VP-silica nanocomposite particles (with silica shells at full monolayer coverage) leads to the facile redistribution of the silica nanoparticles such that partial coverage of all the P2VP latex particles is achieved. This silica exchange, which is complete within 1 h at 20 degrees C as judged by small-angle x-ray scattering, is observed for nanocomposite particles prepared by heteroflocculation, but not for nanocomposite particles prepared by in situ copolymerization. These observations are expected to have important implications for the optimization of nanocomposite formulations in the coatings industry.

When does silica exchange occur between vinyl polymer-silica nanocomposite particles and sterically stabilized latexes?

The redistribution of silica nanoparticles between "core-shell" polymer-silica nanocomposites and sterically stabilized latexes is investigated using a combination of electron microscopy, disk centrifuge photosedimentometry (DCP), and X-ray photoelectron spectroscopy (XPS). Facile exchange of silica nanoparticles occurs on addition of sterically-stabilized polystyrene (or poly(2-vinylpyridine)) latex to polystyrene-silica (or poly(2-vinylpyridine)-silica) nanocomposite particles previously prepared by heteroflocculation. In contrast, no silica exchange occurs after such a latex "challenge" if similar polymer/silica nanocomposite particles are prepared via in situ polymerization. Silica redistribution can be confirmed by post mortem electron microscopy studies, which are facilitated if the original nanocomposite and latex particles differ sufficiently in their mean diameters. Ideally, XPS requires a unique elemental marker for the nanocomposite particle cores, which become progressively more exposed if silica exchange occurs. DCP is a particularly convenient in situ technique for assessing whether or not silica exchange has occurred. If no silica exchange occurs, there is little or no change in the nanocomposite and latex size distributions. On the other hand, silica redistribution always results in a larger mean particle diameter for the (partially) silica-coated latex particles relative to the original bare latex. In addition, incipient flocculation is typically observed after silica exchange. Like electron microscopy, DCP studies are aided if there is a significant difference in particle diameter between the original polymer-silica nanocomposite particles and the added latex. Moreover, silica redistribution can be prevented for heteroflocculated polymer-silica nanocomposite particles under certain conditions. For example, although silica exchange is observed at pH 10 when adding sterically-stabilized polystyrene (or poly(2-vinylpyridine)) latex to heteroflocculated poly(2-vinylpyridine)-silica particles, it does not occur at pH 5. Presumably, this is due to greater electrostatic attraction between the cationic P2VP cores and the anionic silica nanoparticles at this lower pH.

The mammalian orthoreovirus bicistronic M3 mRNA initiates translation using a 5' end-dependent, scanning mechanism that does not require interaction of 5'-3' untranslated regions.

Mammalian orthoreovirus mRNAs possess short 5' UTR, lack 3' poly(A) tails, and may lack 5' cap structures at late times post-infection. As such, the mechanisms by which these viral mRNAs recruit ribosomes remain completely unknown. Toward addressing this question, we used bicistronic MRV M3 mRNA to analyze the role of 5' and 3' UTRs during MRV protein synthesis. The 5' UTR was found to be dispensable for translation initiation; however, reducing its length promoted increased downstream initiation. Modifying start site Kozak context altered the ratio of upstream to downstream initiation, whereas mutations in the 3' UTR did not. Moreover, an M3 mRNA lacking a 3' UTR was able to rescue MRV infection to WT levels in an siRNA trans-complementation assay. Together, these data allow us to propose a model in which the MRV M3 mRNA initiates translation using a 5' end-dependent, scanning mechanism that does not require the viral mRNA 3' UTR or 5'-3' UTRs interaction.

Packing efficiency of small silica particles on large latex particles: a facile route to colloidal nanocomposites.

The adsorption of small silica particles onto large sterically stabilized poly(2-vinylpyridine) [P2VP] latex particles in aqueous solution is assessed as a potential route to nanocomposite particles with a "core-shell" morphology. Geometric considerations allow the packing efficiency, P, to be related to the number of adsorbed silica particles per latex particle, N. Making no assumptions about the packing structure, this approach leads to a theoretical estimate for P of 86 +/- 4%. Experimentally, dynamic light scattering is used to obtain a plot of hydrodynamic diameter against N, which indicates the conditions required for monolayer coverage of the latex by the silica particles. Transmission electron microscopy confirmed that, at approximately monolayer coverage, calcination of these nanocomposite particles led to the formation of well-defined hollow silica shells. This is interpreted as strong evidence for a contiguous monolayer of silica particles surrounding the latex cores. On this basis, an experimental value for P of 69 +/- 4% was estimated for nanocomposite particles prepared by the heteroflocculation of a 20 nm silica sol with near-monodisperse P2VP latexes of either 463 or 616 nm diameter at approximately pH 10. X-ray photoelectron spectroscopy was used to quantify the extent of latex surface coverage by the silica particles. This technique gave good agreement with the silica packing efficiencies estimated from calcination studies.

Formation of the factory matrix is an important, though not a sufficient function of nonstructural protein mu NS during reovirus infection.

Genome replication of mammalian orthoreovirus (MRV) occurs in cytoplasmic inclusion bodies called viral factories. Nonstructural protein microNS, encoded by genome segment M3, is a major constituent of these structures. When expressed without other viral proteins, microNS forms cytoplasmic inclusions morphologically similar to factories, suggesting a role for microNS as the factory framework or matrix. In addition, most other MRV proteins, including all five core proteins (lambda1, lambda2, lambda3, micro2, and sigma2) and nonstructural protein sigmaNS, can associate with microNS in these structures. In the current study, small interfering RNA targeting M3 was transfected in association with MRV infection and shown to cause a substantial reduction in microNS expression as well as, among other effects, a reduction in infectious yields by as much as 4 log(10) values. By also transfecting in vitro-transcribed M3 plus-strand RNA containing silent mutations that render it resistant to the small interfering RNA, we were able to complement microNS expression and to rescue infectious yields by ~100-fold. We next used microNS mutants specifically defective at forming factory-matrix structures to show that this function of microNS is important for MRV growth; point mutations in a C-proximal, putative zinc-hook motif as well as small deletions at the extreme C terminus of microNS prevented rescue of viral growth while causing microNS to be diffusely distributed in cells. We furthermore confirmed that an N-terminally truncated form of microNS, designed to represent microNSC and still able to form factory-matrix structures, is unable to rescue MRV growth, localizing one or more other important functions to an N-terminal region of microNS known to be involved in both micro2 and sigmaNS association. Thus, factory-matrix formation is an important, though not a sufficient function of microNS during MRV infection; microNS is multifunctional in the course of viral growth.

Guanidine hydrochloride inhibits mammalian orthoreovirus growth by reversibly blocking the synthesis of double-stranded RNA.

Millimolar concentrations of guanidine hydrochloride (GuHCl) are known to inhibit the replication of many plant and animal viruses having positive-sense RNA genomes. For example, GuHCl reversibly interacts with the nucleotide-binding region of poliovirus protein 2C(ATPase), resulting in a specific inhibition of viral negative-sense RNA synthesis. The use of GuHCl thereby allows for the spatiotemporal separation of poliovirus gene expression and RNA replication and provides a powerful tool to synchronize the initiation of negative-sense RNA synthesis during in vitro replication reactions. In the present study, we examined the effect of GuHCl on mammalian orthoreovirus (MRV), a double-stranded RNA (dsRNA) virus from the family Reoviridae. MRV growth in murine L929 cells was reversibly inhibited by 15 mM GuHCl. Furthermore, 15 mM GuHCl provided specific inhibition of viral dsRNA synthesis while sparing both positive-sense RNA synthesis and viral mRNA translation. By using GuHCl to provide temporal separation of MRV gene expression and genome replication, we obtained evidence that MRV primary transcripts support sufficient protein synthesis to assemble morphologically normal viral factories containing functional replicase complexes. In addition, the coordinated use of GuHCl and cycloheximide allowed us to demonstrate that MRV dsRNA synthesis can occur in the absence of ongoing protein synthesis, although to only a limited extent. Future studies utilizing the reversible inhibition of MRV dsRNA synthesis will focus on elucidating the target of GuHCl, as well as the components of the MRV replicase complexes.

Axillary hyperhidrosis: a 5-year review of treatment efficacy and recurrence rates using a new arthroscopic shaver technique.

BACKGROUND: Axillary hyperhidrosis is a chronic condition characterized by excess axillary perspiration. This results in considerable patient morbidity, with no consistently efficacious medical or surgical treatment method described in the literature. METHODS: All cases of axillary hyperhidrosis over a 5-year period were reviewed retrospectively. Data were gathered by a chart review and telephone interview. Inclusion criteria included primary hyperhidrosis, failed conservative therapy, no prior surgical therapy, surgical management using a new arthroscopic shaver technique (R.L.B.-S.), and 6 months of postoperative follow-up. The technique used was consistent between surgeons. Sweating severity was assessed using a subjective numerical rating scale ranging from 1 to 10. Patient demographics, symptom history, results, and complications were analyzed. RESULTS: Average follow-up for 50 patients meeting the inclusion criteria was 28 months. The subjective severity scale demonstrated severity of 9.8 of 10 preoperatively and 2.3 of 10 postoperatively. Three patients (6 percent) reported mild recurrence of symptoms (4.6 of 10), which was not severe enough to seek further treatment. The average follow-up of those patients was 18.5 months. An overall subjective satisfaction of 96 percent was found, with a treatment success rate of 94 percent. Complications were minimal and self-limiting. The average time away from employment was 3.9 days and the average surgical operating room time was 46 minutes. CONCLUSIONS: The authors' new arthroscopic shaver technique is efficacious, with no significant morbidity, a 96 percent satisfaction rate, a subjectively measured 75 percent reduction of sweat, and a recurrence rate of only 6 percent. For cases of primary hyperhidrosis affecting the axilla not amenable to conservative treatment, the authors recommend an arthroscopic shaver technique as the first-line treatment of choice.

Poliovirus CRE-dependent VPg uridylylation is required for positive-strand RNA synthesis but not for negative-strand RNA synthesis.

The cis-acting replication element (CRE) is a 61-nucleotide stem-loop RNA structure found within the coding sequence of poliovirus protein 2C. Although the CRE is required for viral RNA replication, its precise role(s) in negative- and positive-strand RNA synthesis has not been defined. Adenosine in the loop of the CRE RNA structure functions as the template for the uridylylation of the viral protein VPg. VPgpUpU(OH), the predominant product of CRE-dependent VPg uridylylation, is a putative primer for the poliovirus RNA-dependent RNA polymerase. By examining the sequential synthesis of negative- and positive-strand RNAs within preinitiation RNA replication complexes, we found that mutations that disrupt the structure of the CRE prevent VPg uridylylation and positive-strand RNA synthesis. The CRE mutations that inhibited the synthesis of VPgpUpU(OH), however, did not inhibit negative-strand RNA synthesis. A Y3F mutation in VPg inhibited both VPgpUpU(OH) synthesis and negative-strand RNA synthesis, confirming the critical role of the tyrosine hydroxyl of VPg in VPg uridylylation and negative-strand RNA synthesis. trans-replication experiments demonstrated that the CRE and VPgpUpU(OH) were not required in cis or in trans for poliovirus negative-strand RNA synthesis. Because these results are inconsistent with existing models of poliovirus RNA replication, we propose a new four-step model that explains the roles of VPg, the CRE, and VPgpUpU(OH) in the asymmetric replication of poliovirus RNA.