Long-term bladder outcomes using a prescriber pattern scoring system for posterior urethral valves.

BACKGROUND: Urinary drainage for posterior urethral valves can be achieved with valve ablation (VA) or diversion by vesicostomy (VES) or cutaneous ureterostomy (CU). The effect of these interventions on long-term bladder function remains debated, and voiding symptomatology after VES or CU reversal has been poorly characterized. OBJECTIVE: The objective of this study was to examine the prevalence and scope of physician treatment patterns as a surrogate for retention or incontinence symptomatology among PUV patients undergoing primary VA or diversion by VES/CU and determine rates of progression to augmentation. STUDY DESIGN: This is a single-institution retrospective cohort study. Retention Scores (R) were calculated 1 point for: retention behavior (double/timed void), alpha-blocker, intermittent catheterization, or overnight indwelling catheter. Incontinence Scores (I) were calculated 1 point for: incontinence behavior (double/timed void), oral medication, or botulinum toxin. Patients with R score above 3 or I score above 2 were deemed to have severe retention or incontinence symptomatology respectively. End stage bladder (ESB) was defined as need for bladder augmentation. RESULTS: We identified 76 patients between 5 and 40 years old with median follow-up of 14.6 [5.0-40.4) years. There was no difference in the rates of severe retention or incontinence treatment pattern scoring between VA versus VES/CU (Figure). Rates of achieving R(1) status are similar between VA and VES/CU groups, though age of reaching R(1) was younger for those with VES/CU (4.8 years) compared to VA (6.6 years). There was no significant difference in rate of ESB by intervention category VA (9.4%) versus VES/CU (17.4%; p = 0.323). DISCUSSION: Treatment of retention symptomatology was more common than treatment of incontinence symptomatology regardless of primary management, VA or VES/CU. This study also indicates that VES/CU patients were just as responsive as VA patients to conservative treatments (behavioral changes, pharmacotherapy) for any type of bladder symptomatology as the progression to treatment of severe symptomatology and ESB were similar between cohorts. In this cohort, bladder outcomes were not associated with type of urinary diversion (VA or VES/CU). CONCLUSION: Long term bladder outcomes for valve patients demonstrated similar treatment patterns and progression to end-stage bladder regardless of diversion status. Patients went on to ESB approximately 4.4 years after diagnosis at similar rates between groups.

Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

'TB or not TB': the conundrum of pre-European contact tuberculosis in the Pacific.

Tuberculosis (TB) is a major global health threat, infecting one-third of the world's population. Despite this prominence, the age, origin and spread of the disease have been topics of contentious debate. Molecular studies suggest that Mycobacterium tuberculosis 'sensu stricto', the most common strain of TB infecting humans today, originated in Africa and from there spread into Europe and Asia. The M. tuberculosis strains most commonly found across the Pacific and the Americas today are most closely related to European strains, supporting a hypothesis that the disease only reached these regions relatively recently via European sailors or settlers. However, this hypothesis is inconsistent with palaeopathological evidence of TB-like lesions in human remains from across the Pacific that predate European contact. Similarly, genetic evidence from pre-European South American mummies challenges the notion of a European introduction of the disease into the Pacific. Here, we review the complex evidence for the age and origin of TB in the Pacific, and discuss key gaps in our knowledge and how these may be addressed. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Mechanistic modelling supports entwined rather than exclusively competitive DNA double-strand break repair pathway.

Following radiation induced DNA damage, several repair pathways are activated to help preserve genome integrity. Double Strand Breaks (DSBs), which are highly toxic, have specified repair pathways to address them. The main repair pathways used to resolve DSBs are Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). Cell cycle phase determines the availability of HR, but the repair choice between pathways in the G2 phases where both HR and NHEJ can operate is not clearly understood. This study compares several in silico models of repair choice to experimental data published in the literature, each model representing a different possible scenario describing how repair choice takes place. Competitive only scenarios, where initial protein recruitment determines repair choice, are unable to fit the literature data. In contrast, the scenario which uses a more entwined relationship between NHEJ and HR, incorporating protein co-localisation and RNF138-dependent removal of the Ku/DNA-PK complex, is better able to predict levels of repair similar to the experimental data. Furthermore, this study concludes that co-localisation of the Mre11-Rad50-Nbs1 (MRN) complexes, with initial NHEJ proteins must be modeled to accurately depict repair choice.

Clinically relevant nanodosimetric simulation of DNA damage complexity from photons and protons.

Relative Biological Effectiveness (RBE), the ratio of doses between radiation modalities to produce the same biological endpoint, is a controversial and important topic in proton therapy. A number of phenomenological models incorporate variable RBE as a function of Linear Energy Transfer (LET), though a lack of mechanistic description limits their applicability. In this work we take a different approach, using a track structure model employing fundamental physics and chemistry to make predictions of proton and photon induced DNA damage, the first step in the mechanism of radiation-induced cell death. We apply this model to a proton therapy clinical case showing, for the first time, predictions of DNA damage on a patient treatment plan. Our model predictions are for an idealised cell and are applied to an ependymoma case, at this stage without any cell specific parameters. By comparing to similar predictions for photons, we present a voxel-wise RBE of DNA damage complexity. This RBE of damage complexity shows similar trends to the expected RBE for cell kill, implying that damage complexity is an important factor in DNA repair and therefore biological effect.

KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects.

Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.

The repeatability of cognitive performance: a meta-analysis.

Behavioural and cognitive processes play important roles in mediating an individual's interactions with its environment. Yet, while there is a vast literature on repeatable individual differences in behaviour, relatively little is known about the repeatability of cognitive performance. To further our understanding of the evolution of cognition, we gathered 44 studies on individual performance of 25 species across six animal classes and used meta-analysis to assess whether cognitive performance is repeatable. We compared repeatability (R) in performance (1) on the same task presented at different times (temporal repeatability), and (2) on different tasks that measured the same putative cognitive ability (contextual repeatability). We also addressed whether R estimates were influenced by seven extrinsic factors (moderators): type of cognitive performance measurement, type of cognitive task, delay between tests, origin of the subjects, experimental context, taxonomic class and publication status. We found support for both temporal and contextual repeatability of cognitive performance, with mean R estimates ranging between 0.15 and 0.28. Repeatability estimates were mostly influenced by the type of cognitive performance measures and publication status. Our findings highlight the widespread occurrence of consistent inter-individual variation in cognition across a range of taxa which, like behaviour, may be associated with fitness outcomes.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.

Serum Amino Acid Profiling in Patients with Alkaptonuria Before and After Treatment with Nitisinone.

BACKGROUND: Alkaptonuria (AKU) is a rare inherited disorder of the tyrosine metabolic pathway. Our group is evaluating the use of the homogentisic acid-lowering agent nitisinone in patients with AKU. A major biochemical consequence of this treatment is hypertyrosinaemia. Herein we report the concentration of 20 serum amino acids over a 36-month period pre- and post-treatment with nitisinone. METHODS: Fasting serum samples were collected at baseline (pre-nitisinone), 3 (2 mg nitisinone every other day), 6, 12, 24 and 36 (2 mg nitisinone daily) months. Amino acids were measured using the Biochrom 30 high-performance liquid chromatography cation exchange system with ninhydrin detection. RESULTS: Fifty patients [21 female, mean age (±standard deviation) 54.1 (15.6) years (range 25-75); 29 male, mean age 49.3 (11.6) years (range 22-70 years)] were included. Following treatment mean tyrosine concentrations increased seven- to eight-fold (baseline, 69.8 µmol/L; 3 months, 670.7 µmol/L; 6 months, 666.4 µmol/L; 12 months, 692.9 µmol/L; 24 months, 649.4 µmol/L; 36 months, 724.8 µmol/L, p = <0.001 for all visits compared to baseline).At baseline mean phenylalanine, aspartic acid and arginine were outside the normal reference range. Following treatment the ratios of phenylalanine/tyrosine, phenylalanine/large neutral amino acids, arginine/branched chain amino acids and branched chain/aromatic amino acids decreased (p = <0.05), and the tyrosine/large neutral amino acid ratio increased (p = <0.0001). CONCLUSIONS: Marked hypertyrosinaemia was observed following treatment with nitisinone. Noteworthy changes were also observed in the ratio of several amino acids following treatment with nitisinone suggesting that the availability of amino acids for neurotransmitter biosynthesis and liver function may be altered following treatment with nitisinone.

Veterans' views on military tobacco use and tobacco control policy.

National military and veteran service organizations (MVSOs) have the potential to be advocates for stronger military tobacco control. This study consisted of qualitative analysis of interviews with 5 MVSO leaders (or their designees) and 6 focus groups conducted with veterans, to explore the opinions of MVSO leaders and veterans about military tobacco use and tobacco control policy, and to assess their current knowledge, attitudes, and likelihood of engaging with civilian tobacco control. Themes discussed include the impact of tobacco use on the military mission and on veterans; the possibility of stronger military tobacco control policies; and the idea that such policies would affect the rights of military personnel. Participants considered whether tobacco use impacts the military mission in the most literal sense (e.g., giving away patrol locations), ignoring larger scale effects on long term health and costs. While familiar with tobacco's impacts on veterans' health, MVSO leaders did not endorse stronger policies, although some veterans did. Participants were largely unaware of the impact of tobacco use on military readiness. Establishment of better alliances among MVSOs and civilian public health groups for mutual education about tobacco's many negative effects on the military's mission may be necessary to achieve a tobacco-free military.

Detailed evaluation of the upper urinary tract in patients with prune belly syndrome using magnetic resonance urography.

INTRODUCTION: Magnetic resonance urography (MRU) has proven to be useful in the setting of complex urologic anatomy. Prune belly syndrome (PBS) patients are known to have malformed and highly variable urinary tract anatomy due to significant dilation and renal dysplasia. OBJECTIVE: To further characterize the renal and ureteral anatomy and renal function in patients with PBS via MRU. STUDY DESIGN: Children with PBS undergoing MRU (2006-2011) were identified. Studies were performed to evaluate severe hydronephrosis in all patients. Demographics, previous imaging, and MRU findings were collected. A single radiologist reviewed all studies. RESULTS: MRU was performed on 13 boys, with a median age of 29.3 months (IQR 6-97). Two patients underwent >1 study for ureteropelvic junction obstruction (UPJ obstruction) and calyceal diverticulum with a solitary kidney, respectively. Hydroureteronephrosis (HUN) was identified in 12 boys (92%), while one (8%) did not have ureteral dilation. All patients demonstrated morphologic abnormalities beyond HUN as follows: five (38%) renal dysplasia; five (38%) scarring; four (31%) calyceal diverticula; and three (23%) thickened bladder. The median renal transit time (RTT) was 6 min (IQR 3.5-10.5), and >8 min (range 8.5-35) in six patients; one patient was ultimately diagnosed with obstruction. The mean serum creatinine was 0.5 ± 0.3 mg/dl. This summary figure is a coronal excretory phase T1 MRU image demonstrating absence of well-defined calyces and a 5-cm calyceal diverticulum (white arrow). DISCUSSION: This study reports significant anatomic and functional findings on MRU that were not readily apparent when using standard imaging for children with PBS. The high-resolution images and functional data obtained with MRU allowed for visualization of calyceal diverticula and abnormal renal pelvic anatomy not previously described in PBS. In addition, renal dysplasia could be identified with MRU, which is badly characterized in the PBS population outside of renal biopsy studies. Potential limitations of the study included its nature as a small retrospective case series, which limited the ability to compare imaging modalities. Imaging modalities were based on individual clinical needs; therefore, comparison with diuretic renal scintigraphy was limited. CONCLUSION: MRU provided anatomic and functional details of the urinary tract in children with PBS that allowed for characterization of new renal anatomic abnormalities, including the incidence of calyceal diverticula and renal dysplasia, which have not been previously described. While renal scarring, dysplasia and calyceal diverticula were easily discerned on MRU in ten patients, their clinical significance requires longer follow-up in a larger patient population.

Plasma pharmacokinetics of ceftiofur metabolite desfuroylceftiofur cysteine disulfide in holstein steers: application of nonlinear mixed-effects modeling.

Eight clinically normal and drug-naïve Holstein steers were dosed with ceftiofur sodium at 2.2 mg/kg body weight intramuscularly. Doses were given at 24-h intervals for 5 days. Prior to the first dose and after all injections, blood samples were collected serially for determination of plasma concentrations of one of ceftiofur's main metabolites, desfuroylceftiofur cysteine disulfide (DCCD). A nonlinear mixed-effect model was used to analyze the plasma concentration data. A stochastic approximation expectation maximization (SAEM) algorithm in MONOLIX version 4.2.2 was used to approximate the likelihood of the nonlinear mixed-effect model and to estimate the population parameters. In addition, simulation studies were conducted to justify the model and demonstrate how to interpret the model parameters given different scenarios.

Evaluating the success of Nd: YAG laser ablation in the treatment of recalcitrant verruca plantaris and a cautionary note about local anaesthesia on the plantar aspect of the foot.

BACKGROUND: There are various methods advocated for the treatment of verruca plantaris. However, many verrucas do not respond to simple treatment. OBJECTIVE: This study presents our results using Nd: YAG laser ablation therapy for such recalcitrant cases. METHODS: We performed a retrospective audit by sending a questionnaire to all patients with recalcitrant verrucas who had been treated with Nd:YAG laser ablation over the previous 12 months. The questionnaire asked whether treatment had been successful, successful but new lesions had emerged, partially successful with improvement or unsuccessful. A Fontana Nd:YAG laser was used at the following specifications; long pulsed mode with pulse width 25 ms, frequency 1.0 Hz; fluence 240 J/cm(2) and spot size 2 mm. Some patients requested local anaesthesia and had direct infiltration with 0.5% plain lidocaine. RESULTS: Fifty-three of the original 87 patients responded (60.9% response rate) with a male to female ratio of 24:29, mean age of 47 years and an age range between 22-72. Thirty-seven patients reported complete success post treatment (69.8%) and a further five reported improvement. The remaining 11 felt their treatment was unsuccessful. The cure rate was 81.8% in unilateral single cases, 68.1% in unilateral multiple cases and 65% in bilateral cases. Ten patients requested sublesional lidocaine injections of which 4 had skin breakdown after Nd: YAG ablation. CONCLUSION: Nd:YAG laser ablation is effective in the treatment of recalcitrant verruca plantaris. However, we caution against the use of direct local anaesthesia infiltration before laser treatment.

The natural history of the multicystic dysplastic kidney--is limited follow-up warranted?

OBJECTIVE: Imaging of patients with multicystic dysplastic kidney (MCDK) has increased over the past three decades. This increased use of imaging has provided additional insights into the natural history of MCDK. The present study looked at this data for predictors of involution and associated anomalies. METHODS AND MATERIALS: Institutional review board approval was obtained for this retrospective study. The University of Michigan Departments of Urology and Radiology records were searched to identify unilateral MCDK patients during 1980-2012. Available clinical, radiological and surgical records were reviewed, and pertinent data were recorded. The log-rank test and a Cox proportional regression analysis were performed to identify predictors of MCDK involution. Probability of involution over time was assessed using Kaplan-Meier methodology. RESULTS: 301 unilateral MCDKs were identified; 195 (64.8%) were detected antenatally. Of the MCDKs found, 136 (45.2%) were in girls; 160 (53.2%) were right-sided. Mean size at baseline was 5.0 ± 0.2 cm (Mean ± SE). Associated abnormalities included: contralateral ureteropelvic junction obstruction (n = 10; 3.3%); contralateral ureterovesical junction obstruction/primary megaureter (n = 6; 2.0%); ipsilateral VUR (n = 21; 7.0%); contralateral VUR (n = 63; 20.1%); and renal fusion anomaly (n = 4; 1.3%). The cumulative probability of involution was: 9.8% at one year, 38.5% at five years, and 53.5% at ten years of age. Baseline MCDK size was the only significant predictor of involution at bivariate (p < 0.0001) and multivariate (p < 0.0001; HR 0.58 [95% CI: 0.49, 0.69]) analyses. No MCDK developed malignancy during the follow-up period. CONCLUSION: As many MCDKs eventually involute and the risk of associated malignancy appears to be very low, there is no absolute indication for nephrectomy. Based on the data and other recent studies, it is believed that pediatric MCDK patients with no other urologic abnormalities can safely tolerate more limited urological and radiological follow-up.

Factors associated with oral hygiene practices among adults with systemic sclerosis.

OBJECTIVE: To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc). METHODS: In this cross-sectional study, 178 dentate adults with SSc received an oral examination which included measurement of oral aperture, assessment of manual dexterity to perform oral hygiene, as well as completion of the Center of Epidemiological Studies Depression (CES-D) Scale and an oral health-related questionnaire. RESULTS: Multivariable logistic regression modelling showed male, minority and high CES-D scores (i.e. clinically significant symptoms of depression) were associated with less likelihood of participants brushing teeth at least twice daily, but the presence of self-reported dry mouth symptoms increased the likelihood of toothbrushing. Having a dental visit in the past 12 months and use of an adapted flossing or interdental cleaning device were significantly associated with daily dental flossing; however, having difficulty flossing teeth reduced the likelihood of daily flossing. CONCLUSIONS: Overall, demographic variables were strongly associated with toothbrushing frequency, whereas flossing self-efficacy and barriers were strongly associated with dental flossing frequency in adults with SSc. The results suggest that dental health professionals should take mental health into consideration when educating patients with SSc to improve their oral hygiene and consider making referrals for patients exhibiting suspected clinically significant depressive symptoms to mental health professionals for further evaluation and treatment. In addition, an appropriate adapted flossing or interdental cleaning device should be recommended to increase dental flossing practices in this patient population.

Proteomic analysis of differentially expressed proteins in caprine milk during experimentally induced endotoxin mastitis.

The goal of the current study was to identify proteins in goat milk before and at 18 h following intramammary challenge with lipopolysaccharide (LPS). Initial evaluation of protein profiles generated using 2-dimensional gel electrophoresis on skim milk samples from a group of 6 goats collected before challenge and at 18, 24, and 48 h after LPS challenge revealed little change in the abundance of casein proteins, and minimal changes in the presence or abundance of the plasma protein serum albumin, which is known to leak into milk during coliform mastitis in dairy cattle. Proteins in baseline milk samples and in milk from the same goats 18 h post-LPS challenge were excised from the gels, and peptides were sequenced using nano-flow liquid chromatography coupled with tandem mass spectrometry. Despite the overwhelming presence of casein proteins and ß-lactoglobulin, the lower abundance proteins ß-2-microglobulin, fatty acid-binding protein, serum albumin, and retinol-binding protein were detected in skim milk samples from healthy goats. Skim milk samples 18 h postchallenge were characterized by the sustained presence and abundance of the casein proteins, and by the presence of haptoglobin, serum amyloid A, lactoferrin, cathelicidin-1, and cathelicidin-3. No marked differences in the intensity of the spot corresponding to serum albumin were observed in gels of skim milk samples 18 h postchallenge, which could indicate that the breakdown of the blood-milk barrier during endotoxin mastitis may not be as profound in goats as has been observed in dairy cattle. Nonetheless, the occurrence of an inflammatory response was supported by elevated somatic cell counts in the goat milk following inoculation with endotoxin, as well as by the presence of both antimicrobial and acute phase proteins. The results provide information about the composition of proteins in goat milk as well as added knowledge of the host response during endotoxin mastitis in goats.

Acclimation to decompression sickness in rats.

Protection against decompression sickness (DCS) by acclimation to hyperbaric decompression has been hypothesized but never proven. We exposed rats to acclimation dives followed by a stressful "test" dive to determine whether acclimation occurred. Experiments were divided into two phases. Phase 1 rats were exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid decompression on one of the following regimens: 70 ft of seawater (fsw) for 9 days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days (S40), or unpressurized sham exposure for 9 days (Control). On the day following the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid decompression). Both L70 and S70 rats had significantly lower incidences of DCS than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the other regimens were lower than in Control rats but without statistical significance. Phase 2 used the most protective regimen from phase 1 (L70); rats were exposed to L70 or a similar regimen with a less stressful staged decompression. Another group was exposed to a single acclimation dive (70 fsw/30 min) on the day before the test dive. We observed a nonsignificant trend for the rapidly decompressed L70 dives to be more protective than staged decompression dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not provide protection. We conclude that protection against DCS can be attained with acclimating exposures that do not themselves cause DCS. The deeper acclimation dive regimens (70 fsw) provided the most protection.

Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro.

Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal role in the initiation of immune responses. Here we report that the murine mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5. Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3 or 4 respectively, induced nuclear translocation of NFkappaB and secretion of CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor cells with the TLR agonists did not modulate growth or viability of the tumor cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3 additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5 and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1 tumors exhibited decreased growth rates in vivo, but not in vitro. These data indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary carcinomas responded to LPS treatment in a manner that decreased tumor growth in vivo.

Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis.

OBJECTIVE: To examine the association of smoking with clinical and serological features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). METHODS: In African Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current versus past versus never and pack-years of exposure) with anti-cyclic citrullinated peptide antibody, rheumatoid factor (RF) (IgM and IgA), rheumatoid nodules and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes. RESULTS: Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05 to 2.88) and nodules (OR = 2.43; 95% CI 1.13 to 5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-cyclic citrullinated peptide antibody, IgM-RF or radiographic erosions. There was also no evidence of a biological or statistical SE-smoking interaction for any of the outcomes examined. CONCLUSIONS: This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population.