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Background: Spinal cord injury (SCI) healthcare providers are aware of the harmful consequences of overweight/obesity in persons with SCI, but many are unaware of available information and lack training to guide weight management care in the SCI population., Objective: Describe the development and content of an educational curriculum for healthcare providers to help individuals with SCI prevent or manage overweight/obesity., Methods: The biopsychoecological framework guided curriculum planning, data collection, and product development. Thematic analysis of interviews conducted with individuals with SCI, informal caregivers, and SCI healthcare providers pinpointed central educational curriculum topics. SCI healthcare providers evaluated the curriculum., Results: Seven comprehensive topics were developed: 1. Scope and consequences of overweight/obesity in SCI; 2. Classifying and measuring overweight/obesity in SCI; 3. Guidelines related to weight management in SCI; 4. Identifying challenges (and solutions) to weight management in SCI; 5. Strategies for providers to facilitate weight management; 6. Understanding goals, motivators, and desired feedback for weight management; and 7. Knowing how informal caregivers are affected by weight and weight management of care recipients with SCI. High ratings (>80% strong agreement) were achieved on content, word choice, organization, relevance, and actionability. Modification needs were identified and subsequently made to layout, visual aids, and provision of tangible resources. Providers described the curriculum as a scientifically rigorous resource that addresses a knowledge gap, provides population-specific content, and is useful across interdisciplinary teams., Conclusion: We developed a self-directed learning educational curriculum addressing topics most salient to stakeholders involved in overweight/obesity management of persons with SCI., (Published by Elsevier Inc.)

Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet few eligible high-risk patients receive it annually. This protocol describes a community-partnered intervention (Toolkit) designed to support primary care practices in making referrals for lung screening and guiding patients into appropriate screening pathways. This study uses a stepped-wedge implementation design. Screening centers are randomized by readiness level to enter the intervention phase in three-month "steps" with pre-intervention data serving as the control. The primary outcome is whether delivery of the Toolkit to primary care practices results in a monthly increase in number of initial LDCT screenings. Six participating centers will identify 10 practices and reach 2-3 providers per practice to train them to use the Toolkit. The Toolkit will address known barriers to screening and referral at the patient and provider levels and provide support for required elements of screening. Toolkit components include adaptable evidence-based interventions to maximize compatibility with workflows. We hypothesize that after nine months of intervention delivery, the number of initial screening per center will double. Involving 60 practices achieves 80% power at 5% level of significance. Implementation outcomes such as adoption, acceptability, feasibility, adaptation, and sustainability will be assessed through field-notes and activity logs. LDCT for lung cancer screening currently reaches a small fraction of eligible adults. To reach the full potential to reduce mortality, primary care practices are an important venue for increasing appropriate referrals. This multidisciplinary trial will encourage acceptability and sustainability by using local knowledge and promoting partnership between providers and patients. Trial registration: ClinicalTrials.gov, NCT03958253., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations., Methods: Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity., Results: For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer ≥1:160, suggesting potential diagnostic capability of this assay., Conclusions: The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the factors most important to applicants when selecting an ophthalmology residency program., Design: Cross-sectional survey., Participants: All 595 applicants who submitted a rank list to the Ophthalmology Residency Matching Program for the 2012 match., Methods: Participants anonymously completed a 25-item questionnaire after the submission of their rank lists. A multiple-choice format and ordinal scale were used to query applicants on demographics, career plans, and the importance of factors related to program characteristics. One question allowed a free text response to identify factors that caused the applicant to rank a program lower than other programs or not at all (i.e., "red flag")., Main Outcome Measures: Factors important to applicants when creating their rank lists., Results: The response rate was 37% (218/595). The 3 most important factors affecting rank lists were resident-faculty relationships, clinical and surgical volume, and diversity of training. The fourth most important was the interview experience with faculty; poor interview experience was the most frequently cited "red flag." Age, gender, and marital status did not affect how applicants rated factors. Applicants planning a post-residency fellowship or an academic career placed greater importance on opportunities for resident research and a program's prestige (P<0.0001). Female and ethnic minority applicants placed greater importance on the diversity of faculty and residents by gender or ethnicity (P<0.0001)., Conclusions: Applicants rated educational and interpersonal factors as more important than geographic factors when selecting an ophthalmology residency program. Future career plans and demographic factors influenced the rating of specific factors. The results of this study provide a useful resource to programs preparing for the match., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the prevalence and incidence of ophthalmic pathology from a small, rural town in Haiti and to determine the leading causes of blindness in this population., Design: Retrospective study from 2002 to 2009. Data collected include visual acuity, intraocular pressure, and ocular and family history., Method: The study was conducted in a single center--Hospital de Lascahobas, Lascahobas, Haiti. Patients were natives of Lascahobas and the surrounding areas. Treatments were dispensed as indicated or warranted., Results: A total of 3702 patients were seen and examined: 51.52% were male and 49.48% were female. Ages ranged from 6 months to 92 years (mean, 48.69 SD +/- 49.94). Uncorrected refractive error was the most common diagnosis (53.27%), followed by presbyopia (43.76%), hyperopia (34.03%), and myopia (22.21%). A total 981 patients (26.50%) were diagnosed with cataract. Three hundred twenty-three (32.93%) cataract surgeries were performed. The overall postoperative complications rate was 9.29%. A total of 706 patients (19.07%) were diagnosed with glaucoma: 23.65% were glaucoma suspect and 76.35% were diagnosed with open-angle glaucoma (POAG). Of those diagnosed with POAG, 35.06% had end-stage (absolute) glaucoma. The mean age at diagnosis was 52.56 SD +/- 8.2 years. The mean intraocular pressure was 24.07 and 25.60 mm Hg, and the mean cup to disc ratio of the right eye (OD) and the left eye (OS), respectively, was 0.67 and 0.72., Conclusions: Glaucoma was the most common cause for blindness. The most common cause of correctable vision loss was uncorrected refractive error followed by cataract. Providing constant eye care in this region will most likely decrease the incidence of correctable and permanent vision loss.

Purpose: To determine the match rate and predictors of matching into an ophthalmology residency., Design: Population-based, cross-sectional study., Participants: All 746 candidates who submitted an application for the 2011 ophthalmology residency match., Methods: The Ophthalmology Residency Matching Program applicant database was reviewed to determine applicant characteristics and match outcomes. For US seniors, multivariate regression analysis was performed to determine predictors of matching., Main Outcome Measures: Match rate and predictors of US seniors matching., Results: Rank lists were submitted by 622 applicants, among whom 458 (74%) matched. The match rate was higher for US seniors (83%) than for independent applicants (41%; P < 0.001). US seniors who matched were more likely to be Alpha Omega Alpha medical honor society members (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.16-7.29), to attend medical schools ranked in the top 40 according to National Institutes of Health funding (OR, 2.25; CI, 1.14-4.43), and to have ranked more programs (OR, 1.44; CI, 1.29-1.60). Those ranking 6 to 10 programs had an 80% to 90% chance of matching, and those ranking more than 10 programs had a greater than 90% chance of matching. No clear benefit was observed by ranking additional programs once 11 had already been ranked. Average US Medical Licensing Examination Step 1 scores were 239 ± 14 and 223 ± 18 for applicants who were matched and unmatched, respectively; this difference was significant by univariate analysis (P < 0.001) but not by multivariate regression (P = 0.163)., Conclusions: Ophthalmology ranks among the most competitive specialties in medicine. Those most likely to match were US seniors who maintained academic excellence beginning in their preclinical years. A finite relationship exists between ranking a greater number of programs and having a greater chance of matching., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Vascularized composite allograft (VCA) transplantation (also referred to as composite tissue allotransplantation) has demonstrated clinical success in cases of hand, arm and face transplantation despite prior belief that skin provides an insurmountable barrier to allograft rejection. These overall good outcomes are facilitated by substantial immunosuppressive requirements in otherwise healthy patients, yet still demonstrate frequent rejection episodes. We developed a nonhuman primate model of facial segment allotransplantation to elucidate the unique pathophysiology and immunosuppressive requirements of VCA with addition of concomitant vascularized bone marrow (VBM). Heterotopically transplanted facial segment VCA with VBM treated only with tacrolimus and mycophenolate mofetil (MMF) demonstrated prolonged rejection-free survival, compared to VCA without VBM that demonstrated early rejection episodes and graft loss. While VCA with VBM demonstrated sporadic macrochimerism, acute and chronic rejection and graft loss occurred after discontinuation of immunosuppression. These data support an immunomodulatory role of VBM in VCA that reduces immunosuppressive requirements while providing improved outcomes., (2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Lower extremity chronic venous disease is due to venous hypertension resulting from reflux and/or obstruction. Studies of venous valvular function have validated and quantified valve closure times defining normal and abnormal valve function, and investigators have categorized the amount of venous reflux with validated criteria. However, hemodynamics of venous outflow obstruction remains poorly defined. The purpose of this study is to assess whether chronic venous disease alters arterial inflow at rest or during hyperemic limb challenge, and whether there are differences in patients with primary chronic venous insufficiency (1 degrees CVI) versus those with postthrombotic venous disease., Methods: Twenty-two normal limbs and 32 limbs in patients with chronic venous disease (C-3 or greater) were examined between September 2006 and January 2008. Chronic venous disease patients consisted of 22 postthrombotic patients and 10 with 1 degrees CVI. Arterial inflow was measured at rest using venous occlusion plethysmography and after induced arterial inflow using postocclusive reactive hyperemia (PORH). Volume changes were recorded with volume plethysmography. A minimum of 10 minutes elapsed between the resting and PORH measurements of arterial inflow., Results: Resting arterial inflow was greater in patients with 1 degrees CVI when compared to normal patients (2.81 vs 1.26, P = .008) and to patients with postthrombotic venous disease (2.81 vs 1.13, P = .03). There was a 7.3-fold increase in maximal arterial inflow in normal patients during PORH versus a 4.8-fold increase in patients with postthrombotic venous disease (P = .015). Patients with 1 degrees CVI had a marked attenuation of maximal arterial inflow during hyperemic limb challenge, demonstrating only a twofold increase relative to their baseline resting arterial inflow (P = .08)., Conclusion: Increases in arterial inflow during a hyperemic limb challenge are less robust in patients with postthrombotic venous disease than in normal volunteers. These data suggest that the pain of venous claudication may in part be due to a diminished arterial inflow response.

Venous obstruction is an underappreciated and often unrecognized component of the pathophysiology of symptomatic chronic venous disease (CVD). Moreover, standard methods used to detect venous obstruction, such as maximal venous outflow, are inadequate as they typically test patients at rest and in the supine position when the pathophysiology of CVD is defined in the upright patient performing exercise. This report describes a patient with incapacitating venous claudication in whom standard noninvasive venous function tests were normal and whose phlebography was interpreted as showing no evidence of venous obstruction. A postocclusive reactive hyperemic technique was used to unmask significant outflow obstruction, leading to operative correction and subsequent symptom resolution.

Comparative studies of the secondary structures of six model proteins, adsorbed onto aluminum hydroxide gel (Alhydrogel) or in aqueous solution, were carried out by Fourier transform infrared (FTIR) spectroscopy. The analysis of high-quality spectra of all six model proteins, with a broad range of secondary structure compositions, obtained at 15 mg/ml by the conventional method and at 0.5 and 1.0 mg/ml adsorbed to Alhydrogel revealed that adsorption onto hydrophilic surfaces of aluminum hydroxide particles did not alter the secondary structures of the proteins. The results of this study suggest that adsorbing proteins to Alhydrogel provides a means of obtaining FTIR spectra to study secondary structure and conformational changes of proteins in aqueous solution at very low concentrations. The new procedure effectively lowers the concentration requirement for FTIR studies of proteins in aqueous solutions by at least 40-fold, as compared with the conventional FTIR method. It permits FTIR study of proteins to be carried out in the same concentration range as is used for circular dichroism and fluorescence, thereby making it possible to compare structural information obtained by three commonly used techniques in protein biophysical characterization.

Prior to delivery to the patient, protein pharmaceuticals often come in contact with a variety of surfaces (e.g., syringes and stoppers), which are treated to facilitate processing or to inhibit protein binding. One such coating, silicone oil, has previously been implicated in the induction of protein aggregation. We have investigated the propensity of model proteins to aggregate when silicone oil is present in solution and find significant induction of aggregation in four proteins of various molecular weights and isoelectric points in the presence of 0.5% oil. The ability of silicone oil to induce conformational changes that might be responsible for this aggregation was also examined by a combination of circular dichroism (CD) and derivative UV spectroscopy. Neither method produces evidence of large conformational changes or alterations in thermal stability although in a limited number of cases some small changes suggest the possibility of minor structural alterations. The most probable explanation for silicone oil induced aggregation is that the oil has direct effects on intermolecular interactions responsible for protein association through interaction with protein surfaces or indirectly through effects on the solvent., (Copyright (c) 2005 Wiley-Liss, Inc.)

Benzyl alcohol, an antimicrobial preservative, accelerates aggregation and precipitation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in aqueous solution. The loss of native monomer during incubation at 37 degrees C was determined by analysis of sample aliquots with size exclusion high performance liquid chromatography (SE-HPLC). Benzyl alcohol caused minor perturbation of the tertiary structure of the protein without changing its secondary structure, documenting that the preservative caused a minor shift in the protein molecular population toward partially unfolded species. Consistent with this conclusion, in the presence of benzyl alcohol the rate of H-D exchange was accelerated and the fluorescence of 1-anilinonaphthalene-8-sulfonic acid in the presence of rhIL1ra was increased. Benzyl alcohol did not alter the free energy of unfolding based on unfolding experiments in urea or guanidine HCl. With differential scanning calorimetry it was determined that benzyl alcohol reduced the apparent Tm of rhIL-1ra, but this effect occurred because the preservative lowered the temperature at which the protein aggregated during heating. Isothermal calorimetry documented that the interaction of benzyl alcohol with rhIL-1ra is relatively weak and hydrophobically driven. Thus, benzyl alcohol accelerates protein aggregation by binding to the protein and favoring an increase in the level of partially unfolded, aggregation-competent species. Sucrose partially inhibited benzyl alcohol-induced aggregation and tertiary structural change. Sucrose is preferentially excluded from the surface of the protein, favoring most compact native state species over expanded aggregation-prone forms., ((c) 2004 Wiley-Liss, Inc. and the American Pharmacists Association)

Worldwide vaccination programs against infectious diseases and toxins are estimated to save approximately 3 million lives yearly. Tragically, however, another 3 million individuals (primarily children) die of vaccine-preventable diseases. A significant portion of this problem results from the thermal instability of many of the currently used vaccines. This review argues that modern methods of physical and chemical analysis permit for the first time characterization of the degradative pathways of thermally labile vaccines. A rigorous description of these pathways permit a more rational and systematic approach to the stabilization of vaccines. A direct result of the replacement of currently employed, primarily empirical, approaches to vaccine stabilization with a more molecular-based methodology should be the development of more universally available vaccinations against life-threatening diseases. This has the potential to have a dramatic impact on world health., (Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:218-231, 2003)

We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected., (Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1466-1477, 2001)

We report the successful use of single-shot spinal anaesthesia for elective caesarean section in a multigravid woman with Ehlers-Danlos syndrome, complicated by mitral valve prolapse. This is a rare inherited collagen disorder that has been reported to have a high pregnancy-related morbidity and mortality, particularly from uterine rupture and uncontrolled bleeding from friable vessels, coagulopathy and major vessel rupture. The literature concerning obstetric anaesthetic management for different types of Ehlers-Danlos syndrome and the management of mitral valve prolapse in pregnancy are reviewed.

Metal-induced precipitation of protein therapeutics is being used and further developed as a processing step in protein formulation and may have utility in protein purification and bulk storage. In such processes, it is imperative that native protein structure is maintained and the metal complexation is reversible. In the current study, we investigated the effects of zinc-induced precipitation on recombinant human growth hormone (rhGH) and recombinant human nerve growth factor (rhNGF). On the addition of ethylenediaminetetraacetic acid (EDTA), the precipitates were dissolved, yielding complete recovery of native protein in both cases. Both proteins have specific metal binding sites and require specific molar ratios of zinc to protein to initiate precipitation (zinc:rhGH > 2:1; zinc:rhNGF > 18:1). Furthermore, the secondary structures of both proteins were unperturbed in soluble zinc complexes and zinc-induced precipitates, as measured by infrared and circular dichroism spectroscopies. The soluble zinc complex of rhGH had minor tertiary structural alterations, whereas zinc binding did not alter the tertiary structure of rhNGF. These studies indicated that metal-induced precipitation provides a method to maintain proteins in their native state in precipitates, which may be useful for purification, storage, and formulation., (Copyright 2000 Wiley-Liss, Inc.)

Agitation- and freeze-thawing-induced aggregation of recombinant human factor XIII (rFXIII) is due to interfacial adsorption and denaturation at the air-liquid and ice-liquid interfaces. The aggregation pathway proceeds through soluble aggregates to formation of insoluble aggregates regardless of the denaturing stimuli. A nonionic surfactant, polyoxyethylene sorbitan monolaurate (Tween 20), greatly reduces the rate of formation of insoluble aggregates as a function of surfactant concentration, thereby stabilizing native rFXIII. Maximum protection occurs at concentrations close to the critical micelle concentration (cmc), independent of initial protein concentration. To study the mechanistic aspects of the surfactant-induced stabilization, a series of spectroscopic studies were conducted. Electron paramagnetic resonance spectroscopy indicates that binding is not occurring between Tween 20 and either the native state or a folding intermediate state of rFXIII. Further, circular dichroism spectroscopy suggests that Tween 20 does not prevent the secondary structural changes induced upon guanidinium hydrochloride-induced unfolding. Taken together, these results imply that Tween 20 protects rFXIII against freeze-thawing- and agitation-induced aggregation primarily by competing with stress-induced soluble aggregates for interfaces, inhibiting subsequent transition to insoluble aggregates.

[125I]-HEAT has proven useful for in vitro autoradiography as a specific alpha 1-adrenergic radioligand. We compared the binding of [125I]-HEAT to membranes from ten brain regions with the densitometric readings of these regions in autoradiographs. There was an excellent correlation between receptor numbers from membrane binding and relative optical densities from the autoradiography. The affinity of HEAT for binding to membranes from various regions was similar. The results of this direct comparison are further evidence that HEAT binds to alpha 1-adrenergic receptors in lightly fixed tissue sections. A further interesting observation is that in regions with a heterogeneous distribution of binding sites, membrane binding may not reflect the presence of a dense local population of receptors.

As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.