Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe. European Consortium on Rheumatoid Arthritis Families

OBJECTIVE: It has been proposed that noninherited maternal antigens (NIMA) (HLA-DR antigens) might play a role in susceptibility to rheumatoid arthritis (RA), especially in patients who are not genetically predisposed, such as those who are HLA-DR4 and/or shared epitope (SE) negative. The present study was undertaken to test the NIMA hypothesis in a large cohort of European RA patients assembled by the European Consortium on RA Families (ECRAF). METHODS: HLA-DRB1 oligotyping was performed in families of European RA patients for whom both parents were alive. These families were consecutively recruited by the ECRAF between 1996 and 1998, for association studies. The frequencies of HLA-DR NIMA were compared with those of the noninherited paternal antigens (NIPA) after stratification for HLA-DR*04, *0401 and/or *0404, and SE status. NIMA or NIPA that coincided with inherited HLA-DR antigens were considered redundant and excluded from analysis. Calculations concerning the whole group and restricted to patients lacking parental RA were performed. RESULTS: One hundred seventy families from France (n = 81), Belgium (n = 23), Spain (n = 24), Italy (n = 19), Portugal (n = 14), and The Netherlands (n = 9) were oligotyped. The group of probands was predominantly female (88%), positive for rheumatoid factor, DR*04, and SE (71%, 58%, and 75%, respectively), and had erosive disease (75%). Parental RA was reported in 21 families. Using the NIPA as control, the frequency of HLA-DRB1*04, *0401 and/or *0404-, or SE-positive NIMA was not found to be increased in patients lacking these susceptibility alleles. The same was true when the 21 probands with parental RA were excluded from analysis. In DRB1*04-positive patients, we found no evidence of a relevant effect of HLA-DR3 or DR6 in the NIMA. CONCLUSION: Our results do not support the notion that noninherited maternal antigens have a role in susceptibility to RA in the offspring.     

Prevalence,risk factors and underdiagnosis of asthma and wheezing in adults 40 years and older: A population-based study

Objective: There are differences in the prevalence and risk factors of asthma around the world. The epidemiological situation of adults 40 years and older is not well established. Our aim was to determine the prevalence, underdiagnosis and risk factors of asthma and wheezing in adults in Colombia. Methods: A cross-sectional, population-based study including 5539 subjects from 40 to 93 years selected by a probabilistic sampling technique in five cities was conducted. Measurements: respiratory symptoms and risk factors questionnaire and spirometry. Definitions: (a) Wheezing: Affirmative answer to the question “have you ever had two or more attacks of “wheezes” causing you to feel short of breath?” (b) Asthma: Wheezing definition and FEV₁/FVC post-bronchodilator?≥?70%. (c) Underdiagnosis: Asthma definition without a physician-diagnosis. Logistic regression was used for exploring risk factors. Results: Prevalence of asthma was 9.0% (95% CI: 8.3-9.8) and wheezing 11.9% (95% CI: 11.0-12.8). Asthma underdiagnosis was 69.9% and increased to 79.0% in subjects 64 years or older. The risk factors related to asthma and/or wheezing were: living in Bogota or Medellin, female gender, first degree relative with asthma, respiratory disease before 16 years of age, obesity, no education, indoor wood smoke exposure and occupational exposure to dust particles, gases or fumes. Conclusion: We described the epidemiologic situation of asthma in adults 40 years and older in Colombia. In addition to some recognized risk factors, our data supports the association of indoor wood smoke and occupational exposures with asthma and wheezing. Underdiagnosis of asthma in adults was high, particularly in older subjects.     

Ultrasensitive gas detection of large-area boron-doped graphene

Heteroatom doping is an efficient way to modify the chemical and electronic properties of graphene. In particular, boron doping is expected to induce a p-type (boron)-conducting behavior to pristine (nondoped) graphene, which could lead to diverse applications. However, the experimental progress on atomic scale visualization and sensing properties of large-area boron-doped graphene (BG) sheets is still very scarce. This work describes the controlled growth of centimeter size, high-crystallinity BG sheets. Scanning tunneling microscopy and spectroscopy are used to visualize the atomic structure and the local density of states around boron dopants. It is confirmed that BG behaves as a p-type conductor and a unique croissant-like feature is frequently observed within the BG lattice, which is caused by the presence of boron-carbon trimers embedded within the hexagonal lattice. More interestingly, it is demonstrated for the first time that BG exhibits unique sensing capabilities when detecting toxic gases, such as NO₂ and NH₃, being able to detect extremely low concentrations (e.g., parts per trillion, parts per billion). This work envisions that other attractive applications could now be explored based on as-synthesized BG.Graphene is a fascinating material that has created an unprecedented impact in condensed-matter physics, chemistry, materials science, and industry (1–6). According to theory, the valence and conduction bands of pristine (nondoped) graphene (PG) touch at the K point in the Brillouin zone, thus making it behave as a zero-overlap semimetal (7). This lack of band gap limits graphene applications in some areas including semiconductor electronics. Therefore, it is crucial to tailor the electronic properties of graphene and eventually be able to open an electronic band gap. Doping, especially chemical doping, constitutes an efficient way to modify the electronic, chemical, and magnetic properties of materials. Recently, exciting progress has been achieved regarding graphene chemical doping, and more detailed information can be found in the literature (8, 9). Among different dopants, the two most adjacent neighbors of carbon in the periodic table of the elements (i.e., B and N) have attracted the attention of numerous scientists because of their similar atomic sizes with C and potential to induce p-type (boron) and n-type (nitrogen) conduction in graphene. In particular, the synthesis of N-doped graphene (NG) (10–14), as well as its atomic scale characterization (15–18) and possible applications (19–21), have been well explored. However, experimental progress on boron-doped graphene (BG) (22–27) is still very scarce compared with that on NG. Actually, theoretical work on BG has been extensively carried out to demonstrate the properties of BG and its possible applications, including field-effect transistors (FETs) (28), hydrogen storage (29), and Li-ion batteries (LIBs) (30). In particular, density functional theory (DFT) calculations predicted that FETs fabricated with BG could exhibit high ON/OFF ratios and low subthreshold swings (28). Moreover, B atoms embedded within the graphene lattice can lead to improved hydrogen storage capacity by decreasing the H₂ adsorption energy dramatically (29). Compared with PG, more Li ions could be captured around boron-doping sites in BG because of the formation of an electron-deficient structure. In this context, Yakobson et al. have demonstrated that the substitutional doping of boron in graphene could lead to much improved Li storage performance with small volume variation during discharge/charge cycles and a capacity of 857 mAh/g (as Li_1.5C₃B), which is two times higher than that of graphite (372 mAh/g) (30). Besides that, it has been theoretically demonstrated that BG could break the symmetry of spin-up and spin-down transmittance channel, thus leading to a metallic-to-semiconductor transition. In this sense, it is believed that BG could become a good candidate for developing spin filter devices. Moreover, from the theoretical standpoint, it has been recently demonstrated that the sensitivity and selectivity of graphene-based gas sensors could be remarkably enhanced by incorporating dopants or defects within the graphene lattice (31). These results open up the possibility of constructing excellent graphene-based sensors to efficiently detect flammable and toxic gases.To experimentally confirm some of the above-mentioned theoretical predictions, it is important to be able to synthesize large-area, highly crystalline BG in a controllable and reproducible way. Furthermore, it is very important to visualize how B atoms bond to C atoms within the sp² hybridized carbon layer to understand the electronic and chemical properties of BG. The present work describes the controlled growth of large-area (∼cm²), high-crystallinity BG sheets grown on copper foils by bubbler-assisted chemical vapor deposition (BA-CVD) at atmospheric pressure. Scanning tunneling microscopy/spectroscopy (STM/STS) was used to understand the electronic features associated with boron dopants at the atomic scale. Characteristic croissant-like (or boomerang-like) features within the BG samples were observed via STM, which are very different from the single substitutional B-dopants observed in BG samples synthesized by low-pressure CVD (LP-CVD) routes (23). These features can be attributed to a vacancy-substitution complex involving three quasiadjacent B atoms. This was confirmed by comparing the experimental STM and STS data with corresponding simulations using state-of-the-art first-principles calculations. As a proof-of-concept, it is demonstrated, for the first time to our knowledge, that boron doping in graphene could lead to an enhanced sensitivity when detecting toxic gases, such as NO₂ and NH₃. It is foreseen that the large-area BG sheets described here could result in novel electronic or magnetic properties not reported hitherto.     

Hospitalization causes and outcomes in HIV patients in the late antiretroviral era in Colombia

Background

Antiretroviral therapy (ART) has modified the natural history of HIV-infection: the incidence of opportunistic infections (OIs) has decreased and mortality associated to HIV has improved dramatically. The reasons for hospitalization have changed; OIs are no longer the most common reason for admission. This study describes the patient population, admission diagnosis and hospital course of HIV patients in Colombia in the ART era.

Methods

Patients admitted with HIV/AIDS at six hospitals in Medellin, Colombia between August 1, 2014 and July 31, 2015 were included. Demographic, laboratory, and clinical data were prospectively collected.

Results

551 HIV-infected patients were admitted: 76.0% were male, the median age was 37 (30–49). A new diagnosis of HIV was made in 22.0% of patients during the index admission. 56.0% of patients of the entire cohort had been diagnosed with HIV for more than 1 year and 68.9% were diagnosed in an advanced stage of the disease. More than 50.0% of patients had CD4 counts less than 200 CD4 cells/μL and viral loads greater than 100,000 copies. The main reasons for hospital admissions were OIs, tuberculosis, esophageal candidiasis and Toxoplasma encephalitis. The median hospital stay was 14 days (IQR 8–23). Admission to the intensive care unit (ICU) was required in 10.3% of patients and 14.3% were readmitted to the hospital; mortality was 5.4%.

Conclusions

Similar to other countries in the developing world, in Colombia, the leading cause of hospitalization among HIV-infected patients remain opportunistic infections. However, in-hospital mortality was low, similar to those described for high-income countries. Strategies to monitor and optimize the adherence and retention in HIV programs are fundamental to maximize the benefit of ART.

     

Clinical relevance of dimensional bone and soft tissue alterations post‐extraction in esthetic sites

The key to achieving pleasing esthetics in implant dentistry is a thorough understanding of the biological processes driving dimensional bone and soft tissue alterations post‐extraction. The aim of the present report is first to characterize the extent of bone and soft tissue changes post‐extraction and second to identify potential factors influencing tissue preservation in order to facilitate successful treatment outcomes. The facial bone wall thickness has been identified as the most critical factor influencing bone resorption and can be used as a prognostic tool in order to identify sites at risk for future facial bone loss subsequent to tooth extraction. Clinical studies indicated that thin bone wall phenotypes exhibiting a facial bone wall thickness of 1 mm or less revealed progressive bone resorption with a vertical loss of 7.5 mm, whereas thick bone wall phenotypes showed only minor bone resorption with a vertical loss of 1.1 mm. This is in contrast to the dimensional soft tissue alterations. Thin bone wall phenotypes revealed a spontaneous soft tissue thickening after flapless extraction by a factor of seven, whereas thick bone wall phenotypes showed no significant changes in the soft tissue dimensions after 8 weeks of healing. In sites exhibiting a limited bone resorption rate, immediate implant placement may be considered. If such ideal conditions are not present, other timing protocols are recommended to achieve predictable and pleasing esthetics. Socket preservation techniques for ridge preservation utilizing different biomaterials and/or barrier membranes often result in a better maintenance of tissue volumes, although the inevitable biological process of post‐extraction bone resorption and bone modeling cannot be arrested. In summary, the knowledge of the biological events driving dimensional tissue alterations post‐extraction should be integrated into the comprehensive treatment plan in order to limit tissue loss and to maximize esthetic outcomes.     

On the Passivity of Hysteretic Systems with Double Hysteretic Loops

The Bouc–Wen hysteresis model is widely employed to mathematically represent the dynamical behavior of several physical devices, materials and systems such as magnetorheological dampers, lanthanide zirconium or aluminum oxides, mechanical structures or biomedical systems. However, these mathematical models must account for different properties such as the bounded-input bounded-output stability, asymptotic motion, thermodynamic admissibility or passivity in order to be physically consistent with the systems they represent. The passivity of a system is related to energy dissipation. More precisely, a system is passive if it does not generate energy but only dissipates it. The objective of this paper is to prove that two different double-loop Bouc–Wen models are passive under a particular set of model parameters.     

Temporal stability of network centrality in control and default mode networks: Specific associations with externalizing psychopathology in children and adolescents

Abnormal connectivity patterns have frequently been reported as involved in pathological mental states. However, most studies focus on “static,” stationary patterns of connectivity, which may miss crucial biological information. Recent methodological advances have allowed the investigation of dynamic functional connectivity patterns that describe non‐stationary properties of brain networks. Here, we introduce a novel graphical measure of dynamic connectivity, called time‐varying eigenvector centrality (tv‐EVC). In a sample 655 children and adolescents (7–15 years old) from the Brazilian “High Risk Cohort Study for Psychiatric Disorders” who were imaged using resting‐state fMRI, we used this measure to investigate age effects in the temporal in control and default‐mode networks (CN/DMN). Using support vector regression, we propose a network maturation index based on the temporal stability of tv‐EVC. Moreover, we investigated whether the network maturation is associated with the overall presence of behavioral and emotional problems with the Child Behavior Checklist. As hypothesized, we found that the tv‐EVC at each node of CN/DMN become more stable with increasing age (P < 0.001 for all nodes). In addition, the maturity index for this particular network is indeed associated with general psychopathology in children assessed by the total score of Child Behavior Checklist (P = 0.027). Moreover, immaturity of the network was mainly correlated with externalizing behavior dimensions. Taken together, these results suggest that changes in functional network dynamics during neurodevelopment may provide unique insights regarding pathophysiology. Hum Brain Mapp 36:4926–4937, 2015. © 2015 Wiley Periodicals, Inc.