Factors associated with PrEP use in a community sample of African American men who have sex with men (MSM) and transgender women (TGW) in the United States Midwest.

Black sexual minority men who have sex with men (MSM) in the United States are at disparate risk for contracting HIV infection, but pre-exposure prophylaxis (PrEP) use is suboptimal. Social network methods were used to recruit a community sample of racial minority MSM and transgender women (TGW) in two Midwestern US cities. 250 PrEP-eligible (HIV-negative) participants completed measures assessing current and intended PrEP use; demographic characteristics; PrEP knowledge, attitudes, norms, stigma, and self-efficacy; and structural barriers to PrEP. Multivariate analyses established predictors of current and intended PrEP use. Only 12% of participants reported currently using PrEP, which was associated with greater PrEP knowledge and not having a main partner, with trends for greater PrEP use by younger participants and those with partners living with HIV. Among participants not currently on PrEP, strength of PrEP use intentions was associated with higher PrEP knowledge, PrEP descriptive social norms, and PrEP use self-efficacy. This study is among few to directly compare Black who have adopted PrEP with those who have not. Its findings underscore the potential benefits of employing social network approaches for strengthening PrEP use peer norms, increasing PrEP knowledge and self-efficacy, and optimizing PrEP uptake among racial minority MSM and TGW.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Gain-switched semiconductor lasers with pulsed excitation and optical injection for dual-comb spectroscopy.

In this work we demonstrate the capability of two gain-switched optically injected semiconductor lasers to perform high-resolution dual-comb spectroscopy. The use of low duty cycle pulse trains to gain switch the lasers, combined with optical injection, allows us to obtain flat-topped optical frequency combs with 350 optical lines (within 10 dB) spaced by 100 MHz. These frequency combs significantly improve the spectral resolution reported so far on dual-comb spectroscopy with gain-switched laser diodes. We evaluate the performance of our system by measuring the transmission profile of an absorption line of H13CN at the C-band, analyzing the attainable signal-to-noise ratio for a range of averaging times.

Social network intervention to increase pre-exposure prophylaxis (PrEP) awareness, interest, and use among African American men who have sex with men.

In the U.S., HIV incidence is highest among Black men who have sex with men (MSM) but PrEP uptake is low, in part due to lack of normative support for using PrEP. This research pilot tested a social network-level intervention designed to increase PrEP use willingness, interest, and peer supports among Black MSM in Milwaukee. Five community social networks (n = 40 participants) of racial minority MSM were assessed at baseline with measures of PrEP knowledge, interest, attitudes, and action taking. Persons most interconnected with others in each network attended an intervention that provided training to increase knowledge about PrEPbenefits, address PrEP concerns, endorse PrEP use as a symbol of pride and health, and deliver these messages to others in their social networks. All network members were re-administered the same measures at 3-month followup. Significant increases over time were found in network members' PrEP knowledge, attitudes, norm perceptions, self-efficacy, and willingness to use PrEP. Participants more often talked with friends about HIV and with their health care providers about PrEP. The percentage of participants who reported using PrEP increased from 3% to 11%. Larger-scale evaluations of this intervention model are needed.

Enhanced optical frequency comb generation by pulsed gain-switching of optically injected semiconductor lasers.

We report on the experimental generation of broad and flat optical frequency combs (OFC) in a 1550 nm laser diode using gain switching with pulsed electrical excitation together with optical injection. The combination of both techniques allows the generation of high-quality OFCs at a repetition frequency of 500 MHz, showing a low-noise optical spectrum with unprecedent features in terms of width (108 tones within 10 dB) and flatness (56 tones within 3 dB) in comparison with those previously reported for this modulation frequency. The influence of the injection conditions on the OFC quality is studied. Using these two techniques, it has been possible to reduce the separation between tones, generating high spectral performance OFCs with a repetition rateof 100 MHz.

Consensus document on dog and cat allergy.

The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.

Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

Subgingival bacterial community profiles in HIV-infected Brazilian adults with chronic periodontitis.

BACKGROUND AND OBJECTIVE: To compare the subgingival microbial diversity between non-HIV-infected and HIV-infected individuals with chronic periodontitis using denaturing gradient gel electrophoresis (DGGE). MATERIAL AND METHODS: Thirty-two patients were selected: 11 were HIV-infected and 21 were non-HIV-infected, and all had chronic periodontitis. Periodontal measurements included probing depth, clinical attachment level, visible supragingival biofilm and bleeding on probing. Subgingival biofilm samples were collected from periodontal sites (50% with probing depth ≤ 4 mm and 50% with probing depth ≥ 5 mm) and whole-genomic-amplified DNA was obtained. The DNA samples were subjected to amplification of a 16S rRNA gene fragment using universal bacterial primers, followed by DGGE analysis of the amplified gene sequences. RESULTS: The non-HIV-infected group presented higher mean full-mouth visible supragingival biofilm (p = 0.004), bleeding on probing (p = 0.006), probing depth (p < 0.001) and clinical attachment level (p = 0.001) in comparison with the HIV-infected group. DGGE analysis revealed 81 distinct bands from all 33 individuals. Banding profiles revealed a higher diversity of the bacterial communities in the subgingival biofilm of HIV-infected patients with chronic periodontitis. Moreover, cluster and principal component analyses demonstrated that the bacterial community profiles differed between these two conditions. High interindividual and intra-individual variability in banding profiles were observed for both groups. CONCLUSION: HIV-infected patients with chronic periodontitis present greater subgingival microbial diversity. In addition, the bacterial communities associated with HIV-infected and non-HIV-infected individuals are different in structure.

Practical guidelines for diagnosing hypersensitivity reactions to nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity reactions. These reactions include various clinical entities with different mechanisms leading to the release of inflammatory mediators. Characterization of patients based on clinical manifestations and suspected underlying mechanisms is critical for implementation of adequate diagnostic procedures and patient management. Our objectives were to prepare a systematic review of available scientific evidence and to provide general guidelines for the diagnosis and management of patients with hypersensitivity reactions to NSAIDs. We also propose a practical algorithm for the diagnosis of specific types of hypersensitivity to NSAIDs and provide recommendations for the management of hypersensitive patients.

SLIT: indications, follow-up, and management.

Specific sublingual immunotherapy (SLIT) has been proved to be a safe and effective approach in respiratory allergy. However, further research is required on aspects such as patient selection, use of optimal dosing, effects on asthma, long-term effects, and management of adverse reactions. In addition, the widely heterogeneous nature of studies on SLIT performed to date and the application of the criteria for subcutaneous immunotherapy make it difficult for the prescribing clinician to draw accurate and useful conclusions. Therefore, the QUASAR Group (QUality in the Administration of SLIT in Allergic Rhinitis), which comprises allergologists with broad clinical experience in SLIT, investigated the latest research findings and available data on this approach. Working parties were formed in 3 different categories: selection of candidates for SLIT, treatment efficacy, and adverse reactions. We performed a PubMed search for articles that were representative of each category and found 850. From these, we finally selected 266 articles, which were reviewed to retrieve data on SLIT. Evidence for each clinical question was graded according to the Oxford classification. The resulting text was evaluated on 3 occasions by all the members of the group until the final version was agreed upon. In this version, we review available evidence on SLIT, particularly with pollens, which is the subject of most articles. In areas where evidence is insufficient, an alternative agreed upon by the members of the QUASAR group is presented. Finally, we propose algorithms for selecting candidates for SLIT and for management of adverse events.

Clinical antimicrobial efficacy of NiTi rotary instrumentation with NaOCl irrigation, final rinse with chlorhexidine and interappointment medication: a molecular study.

AIM: To evaluate clinically the antibacterial effects of root canal treatment procedures using molecular microbiology analyses. METHODOLOGY: Samples were taken from 14 necrotic root canals of teeth with apical periodontitis before (S1) and after instrumentation with NaOCl irrigation (S2), a final rinse with chlorhexidine (CHX) (S3) and then one-week interappointment medication with calcium hydroxide/CHX paste (S4). The parameters examined included the following: incidence of positive broad-range PCR results for bacterial presence; impact on bacterial community structures evaluated by PCR-Denaturing Gradient Gel Electrophoresis (DGGE); quantitative bacterial reduction determined by real-time PCR; and identification of bacterial persisters by cloning and sequencing. Data from the different tests were subjected to statistical analyses and diversity indicator calculations. RESULTS: All S1 samples were positive for bacteria in all tests. Treatment procedures promoted a decrease in microbial diversity and significantly reduced the incidence of positive results and the bacterial counts (P < 0.05). In general, each subsequent treatment step improved disinfection. No specific taxon or community pattern was associated with post-treatment samples. CONCLUSION: Supplementary steps consisting of a final rinse with CHX followed by calcium hydroxide interappointment medication promoted further decrease in the bacterial bioburden to levels significantly below those achieved by the chemomechanical procedures alone. Because the long-term outcome of root canal treatment is dependent upon maximal bacterial reduction, the present results are of clinical relevance.

Knowledge, attitude and adherence of Spanish healthcare professionals to asthma management recommendations during pregnancy.

BACKGROUND: The aim of the present study was to evaluate the knowledge, attitude and adherence to asthma management recommendations during pregnancy of Spanish health care professionals. METHODS: A multiple choice survey with 14 questions was designed. Items assessed opinion about asthma guidelines and attitudes towards treatment, spirometry, specific immunotherapy and labour in pregnant asthmatic patients. Test completion was voluntary, individual, and anonymous. RESULTS: A total of 1000 questionnaires were fulfilled: respiratory medicine specialists (19.8%); allergy specialists (17.2%); primary care physicians (46.1%); and gynaecologists/obstetricians (16.9%). Guidelines were considered useful by 96.5% although 64% admitted that they followed them seldom or never. Most physicians (55.9%) answered that they would maintain asthma therapy in clinically stable patients. Almost 30% of physicians would not perform spirometry in pregnant asthma patients. 19% declared they would interrupt specific immunotherapy which had proven safe and effective. Univariate analysis revealed low adherence to be associated with the following variables: age, primary care or gynaecology/obstetrician specialisation, number of asthmatics attended per month, and declared use of guidelines for pregnant asthmatic patients. Multivariate analysis showed that being a primary care physician and a gynaecologist/obstetrician, attending a low number of asthma patients per month, and poor use of spirometry during pregnancy are associated to low adherence to asthma guidelines. CONCLUSION: Even though the majority of Spanish physicians surveyed seem to consider guidelines useful, their adherence to those is very low if translated to managing pregnant asthmatic patients. Educational strategies seem unavoidable and should be targetted mainly to primary care and gynaecology/obstetrician physicians.

Diversity of the candidate phylum Poribacteria in the marine sponge Aplysina fulva.

Poribacterial clone libraries constructed for Aplysina fulva sponge specimens were analysed with respect to diversity and phylogeny. Results imply the coexistence of several, prevalently "intra-specific" poribacterial genotypes in a single sponge host, and suggest quantitative analysis as a desirable approach in studies of the diversity and distribution of poribacterial cohorts in marine sponges.

Genetic variants of the arachidonic acid pathway in non-steroidal anti-inflammatory drug-induced acute urticaria.

BACKGROUND: To date, genetic studies of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been carried out mainly in aspirin-induced asthma and to a lesser extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs. OBJECTIVE: In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID-induced AU. METHODS: Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross-intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays. RESULTS: A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case-control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p-value ≤ 0.041). A follow-up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10(-6) ≤meta-analysis p-value ≤ 0.003). CONCLUSIONS AND CLINICAL RELEVANCE: Genetic variants of the AA pathway may play an important role in NSAID-induced AU. These data may help understand the mechanism underlying this disease.

Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity reactions to iodinated contrast media.

BACKGROUND: Nonimmediate hypersensitivity reactions to iodinated contrast media (CM) are common. Allergological evaluation is necessary to confirm the diagnosis and to find a tolerated alternative. The aim of this study was to establish the role of skin testing and the drug provocation test (DPT) in the diagnosis of nonimmediate reactions to CM. METHODS: Skin intradermal testing and patch testing with delayed readings were carried out with different CM (iobitridol, iomeprol, iodixanol, iohexol, ioversol, iopramide and ioxaglate). Single-blind placebo-controlled DPT was carried out in those cases with a negative skin test. In seven cases, a skin biopsy was obtained from positive skin tests and positive DPT. RESULTS: Of the 161 subjects evaluated, 34 (21.1%) were skin-test positive, 21 (50%) to Iomeprol, 7 (16.7%) to Iodixanol, 5 (11.9%) to Iobitridol, 4 (9.5%) to Ioxaglate, 3 (7.1%) to Iohexol and 1 (2.4%) to Iopramide. DPT was positive in 44 cases (34.6%) that were skin-test negative, 38 (76%) to Iodixanol, 8 (16%) to Iomeprol and 4 (8%) to Iohexol. Of 78 cases (48.4%) with confirmed hypersensitivity, 34 (43.6%) were identified by skin testing and 44 (56.4%) by DPT. Skin biopsies showed a perivascular mononuclear cell infiltrate, mainly in the dermis, with higher levels of CD4 than CD8 T lymphocytes, with expression of activation markers and skin homing receptors. CONCLUSION: Patients with nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT in 56.4%. The method to confirm the diagnosis differed depending on the CM involved.