Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis.

Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate lower airway disease. We sought to determine whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. We performed 16S rRNA gene sequencing, supplemented with cytokine analyses, microscopy, and bacterial culturing, on samples from the sinuses of 27 adults with CF CRS. At each study visit, participants underwent endoscopic paranasal sinus sampling and clinical evaluation. We identified key drivers of microbial community composition and evaluated relationships between diversity and taxa with disease outcomes and inflammation. Sinus community diversity was low, and the composition was unstable, with many participants exhibiting alternating dominance between Pseudomonas aeruginosa and staphylococci over time. Despite a tendency for dominance by these two taxa, communities were highly individualized and shifted composition during exacerbation of sinus disease symptoms. Exacerbations were also associated with communities dominated by Staphylococcus spp. Reduced microbial community diversity was linked to worse sinus disease and the inflammatory status of the sinuses (including increased interleukin-1ß [IL-1ß]). Increased IL-1ß was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease. IMPORTANCE Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures. This work strongly suggests that clinical management of CRS could be leveraged to improve overall respiratory health in CF. Our work implicates elevated IL-1ß in reduced microbiota diversity and worse sinus disease in CF CRS, suggesting applications for existing therapies targeting IL-1ß. Finally, the widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to less frequent availability of spontaneous expectorated sputum for microbiological surveillance of lung infections. A better understanding of CF sinus microbiology could provide a much-needed alternative site for monitoring respiratory infection status by important CF pathogens.

Adolescents' Understanding of Opioid-Induced Euphoria Measures and Proposed Measurement Revisions.

Prescription opioid misuse is an unintended consequence of acute pain management. Opioid-induced euphoria (OIE) with first therapeutic opioid exposure may influence opioid misuse. OIE is not assessed in clinical care and self-report measures of OIE have not been validated in adolescents. We (1) determined adolescents' ability to understand existing self-reported OIE measures, (2) revised measures for better understanding by this population, and (3) established initial content validity of revised measures with adolescents. Using runner's euphoria to simulate OIE in Study 1, 29 adolescents' (14 males) understanding of the Drug Effects Questionnaire (DEQ-5), the Addiction Resource Center Inventory Morphine Benzedrine Group scale (ARCI-MBG), and the ARCI Lysergic Acid Diethylamide scale (ARCI-LSD) were tested. In Study 2, 29 additional adolescents (9 males) participated in a modified Delphi study with focus groups to revise survey items to improve understanding by peers. In Study 1, runners understood <40% of ARCI-MBG and ARCI-LSD statements. In Study 2, all but 7 survey items were revised. Revised measures of OIE for adolescents may help define at-risk OIE phenotypes and validate risk assessments using survey methodology. Additional studies are needed to validate the revised OIE self-report measures with opioid-naive adolescents receiving opioids to treat acute pain.

Epidemiology of recurrent seizure disorders and epilepsy in cats under primary veterinary care in the United Kingdom.

BACKGROUND: Little epidemiological evaluation of recurrent seizure disorders in cats currently exists in veterinary literature. OBJECTIVES: To report the prevalence and risk factors for recurrent seizure disorders (RSD) and epilepsy in cats presented to primary care veterinary practices in the United Kingdom (UK). ANIMALS: A total of 285 547 cats under veterinary care during 2013 presenting to 282 primary care clinics in the UK. METHODS: Cohort study using multivariable logistic regression modeling for risk factor analysis. RESULTS: There were 458 confirmed RSD cases, giving a 1-year period prevalence of 0.16% (95% confidence interval [CI], 0.15-0.18). A subset of 114 (24.89%) cases was recorded as having epilepsy, giving a 1-year period prevalence of 0.04% (95% CI, 0.03-0.5). Increasing age was significantly associated with increasing odds of RSD. Breed, sex, neuter status, and body weight were not associated with RSD. Epilepsy was most frequently diagnosed in adult to middle-aged cats. Cats aged 3.0 to <6.0 years had 3.32 times higher odds of epilepsy diagnosis compared to cats <3.0 years of age. Insured cats were more likely to be diagnosed with epilepsy compared to noninsured cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Although less common than in dogs, RSD and epilepsy still comprise an important disorder group in the UK cat population. Aging is a significant risk factor for these disorders in cats.

Estimating fat-free mass in elite-level male rowers: a four-compartment model validation of laboratory and field methods.

The purpose of this study was to investigate the accuracy of fat-free mass (FFM) estimates from two-compartment (2C) models including air displacement plethysmography (ADP), ultrasound (US), near-infrared interactance (NIR), and the Jackson and Pollock skinfold equation (SKF) against a criterion four-compartment (4C) model in elite male rowers. METHODS: Twenty-three elite-level male rowers (mean± SD; age 24.6 ± 2.2 years; stature: 191.4 ± 7.2 cm; mass: 87.2 ± 11.2 kg) participated in this investigation. All body composition assessments were performed on the same day in random order, except for hydrostatic weighing (HW), which was measured last. FFM was evaluated using a 4C model, which included total body water from bioimpedance spectroscopy, body volume from HW, and total body bone mineral via dual-energy X-ray absorptiometry. The major findings of the study were that the 2C models evaluated overestimated FFM and should be considered with caution for the assessment of FFM in elite male rowers. Future studies should use multiple-compartment models, with measurement of TBW and bone mineral content, for the estimation of FFM.

Cryofibrinogenemia in a patient with B-cell lymphoma.

Cryofibrinogenemia is an uncommon cause of intravascular coagulation necrosis of the skin and occurs as a result of vascular occlusion from cryoproteins, which reversibly precipitate in cold temperatures. The disease is associated with various conditions, most commonly neoplastic and thromboembolic diseases, and produces cutaneous manifestations such as purpura, ecchymoses, gangrene, and ulcerations. Diagnosis is based on clinical cutaneous manifestations, histopathology, and the laboratory detection of cryofibrinogen precipitation. Treatment is based upon resolution of the underlying disease process or condition, although some interventions have been reported to have therapeutic efficacy. We discuss the presentation, diagnosis, and treatment of a case of cryofibrinogenemia in a patient with underlying B-cell lymphoma.

Systemic lupus erythematosus diagnosed during interferon alfa therapy.

We describe a patient who had clinical manifestations of several autoimmune disorders: Sjögren's syndrome, benign hypergammaglobulinemic purpura of Waldenström, and systemic lupus erythematosus (SLE). The SLE was diagnosed during therapy with interferon alfa. Testing for anti-Ro and anti-La antibodies was negative until the serum was diluted to eliminate a possible prozone phenomenon of antibody excess.

Implications of the SEC's final continuing disclosure rule.

The Securities and Exchange Commission's (SEC's) final disclosure rule affects healthcare providers who have $10 million or more in bonds outstanding and providers that plan to be active in the bond market in the future. As managed care providers, HMOs come under the jurisdiction of the rule and are required to expand their reporting of financial information and operational data to include secondary market bond purchasers. The SEC's broadened disclosure rule significantly affects the financial reporting practices of healthcare providers involved in capitated contracting--especially the areas of contract reporting, confidentiality of information, and catastrophic case loss reporting.

Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies.

The development of an animal model for studying the pathogenesis of pemphigus vulgaris (PV) has been hampered by the unavailability of the purified full-length autoantigen desmoglein 3 (Dsg 3).Therefore, we expressed Dsg 3 using a baculovirus expressed system. The expressed protein was identified as Dgs 3 by its reactivity with a pan-cadherin anti-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that recombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was demonstrated in the medium. The Dgs 3 could adsorb out blister-causing antibodies from patient sera. Rabbit anti- Dsg 3 antibodies induced by the recombinant Dsg 3 showed specific binding to intercellular spaces of monkeys esophagus by indirect immunofluorescence. Moreover, these antibodies induced PV-like blisters in neonatal mice and weakly bound perilesional epidermis. Availability of large quantities of relatively pure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 structure and pathogenesis of PV, with implications for developing specific immunotherapies.

Neonatal pemphigus foliaceus.

BACKGROUND: Pemphigus refers to a group of autoimmune blistering diseases of the skin. Of the two major types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, only pemphigus vulgaris has been known to affect newborn infants via passive transfer of maternal IgG antibodies across the placenta. Although pemphigus foliaceus antibodies have also been shown to cross the placenta, never before has a newborn been clinically affected. We report the first of neonatal pemphigus foliaceus confirmed by both clinical presentation and immunofluorescence studies. OBSERVATIONS: The distinguishing factors in this case were high antibody titers by indirect immunofluorescence present in both the mother and her fetus (1:640 and 1:80, respectively). CONCLUSIONS: A threshold of fetal antibody titer ( > 1:40) may need to be surpassed before neonatal disease can occur in pemphigus foliaceus. The likelihood of reaching this threshold has been shown to be increased with higher maternal antibody titers. Thus, strict control of maternal pemphigus foliaceus should lower the incidence of placental antibody transfer and improve neonatal outcome.

Bullous pemphigoid autoantibodies reactive with intracellular basal keratinocyte antigens: studies of subclass distribution and complement activation.

Using immunofluorescence (IF) and monoclonal antibodies (MoAbs) to IgG subclasses, terminal complement components, and S-protein/vitronectin, we have extended recent observations concerning reactivity of bullous pemphigoid autoantibodies with intracellular antigens located on the polar tips of basal human keratinocytes (HuK). Using three purified bullous pemphigoid IgG fractions, autoantibody reactivity with these intracellular antigens was present in all four IgG subclasses. When skin sections were used as substrate, an identical IgG subclass distribution of autoantibodies for each bullous pemphigoid IgG fraction was observed, but reactive with the basement membrane zone. All three bullous pemphigoid IgG preparations contained IgG subclass autoantibodies capable of complement fixation. Each IgG fraction resulted in fixation of all of the terminal complement components (C5, C6, C7, C8, and C9) and assembly of the membrane attack complex (MAC) on the polar tips of basal HuK. S-protein/vitronectin was not bound in a similar fashion. Normal IgG fractions yielded consistently negative reactions. Thus, bullous pemphigoid autoantibodies, fixed to polar tips of basal HuK, are found in all four IgG subclasses and will activate complement resulting in generation of MAC.

The surgical applications and implications of cultured human epidermis: a comprehensive review.

Replacement of skin has long been the ultimate task for surgeons facing skin-resurfacing challenges such as thermal burns and chronic ulcerations. Autologous skin grafts have been the "gold standard" for wound closure, but in patients who are massively burned, the availability of normal skin is the limiting factor. In the past 15 years the technique of in vitro cultivation of human epidermis has been developed in an attempt to deal with the problem of extensive skin loss. Although the technique is costly and arduous, grafting patients who are severely burned with cultured epidermal autografts has proved to be a life-saving measure where few alternatives exist. Cultured allografts have promoted rapid healing and pain relief in patients with chronic ulcers. Although longer follow-up is necessary, recent evidence suggests that cultured epidermis provides a wound cover that is just as durable and esthetically acceptable as conventional split-thickness skin grafts. This article reviews the development and applications of epidermal cell culture.

Once-daily naftifine cream 1% in the treatment of tinea cruris and tinea corporis.

Seventy patients with tinea cruris or tinea corporis were treated with naftifine cream 1% or vehicle once daily for 4 weeks in this double-blind, randomized study. After two weeks, the patients using naftifine had a significantly higher mycologic cure rate than the vehicle-treated patients (79% vs. 31%, p less than 0.001), and they showed significantly better resolution of signs and symptoms. Statistically significantly differences favoring naftifine over its vehicle were found throughout the treatment period and 2 weeks posttreatment.

Pemphigus immunoglobulin G subclass autoantibodies: studies of reactivity with cultured human keratinocytes.

The subclass distribution of pemphigus vulgaris (PV) autoantibodies has been investigated further. Cultured human keratinocytes (HuKs) were incubated with immunoglobulin G (IgG) fractions prepared from the serum samples of five patients with PV and one patient with pemphigus foliaceus (PF). The binding of IgG subclasses to HuK was detected by the use of indirect immunofluorescence done with monoclonal antibodies that were specific for each of the four human IgG subclasses. IgG1 and IgG4 binding to keratinocytes was detected in all of the pemphigus IgG preparations. In each instance, the titer of bound IgG1 was equal to or greater than the IgG4 titer. IgG3 binding was detected in only one PV IgG, and IgG2 pemphigus antibody activity was not detected. Differences in the immunofluorescence patterns between the five PV and one PF IgG and between the five PV and a second PF serum were noted. PV antigens were detected as a speckled pattern on HuKs, with accentuation in the intercellular spaces. By comparison, the pattern of PF antigen expression varied significantly depending on whether anti-IgG1 or anti-IgG4 antisera were used. Anti-IgG1 bound in a coarse granular pattern without accentuation in the intercellular spaces, but anti-IgG4 bound in a pattern nearly identical to that observed with PV IgG and its subclasses.

Chronic cutaneous lupus erythematosus.

Chronic cutaneous LE is a diverse disease, characterized by predominantly cutaneous disease with few systemic complications. Discoid lesions are commonly seen, but they are not specific for chronic cutaneous LE. These scarring and disfiguring changes are also present in neonatal LE, SLE, and complement deficiency LE. Because definitive diagnosis cannot be made by cutaneous examination alone, all patients should initially be evaluated for systemic disease. A small percentage of patients with chronic cutaneous LE will ultimately develop SLE, and therefore, patients should be re-evaluated periodically. The pathogenesis of the cutaneous lesions is not definitively known. There is suggestive evidence implicating T-cell mediated injury, especially in discoid LE. Antibody-dependent cellular cytotoxicity may also play a significant role in cellular damage in subacute cutaneous LE and neonatal LE, especially in the presence of anti-Ro antibody. Immunoglobulin deposition in association with membrane attack complex, has been associated with epidermal injury in some cases. Treatment of chronic cutaneous LE is largely symptomatic and nonspecific, focusing on reduction of inflammation. Further knowledge of pathogenesis will, hopefully, provide for specific immunologic therapy.