Reasons for missed opportunities to screen and test for TB in healthcare facilities.

Missed opportunities for TB screening and/or passive testing in clinics continues to contribute to the number of missed cases. To understand reasons for these missed opportunities, we conducted focus group discussions with clinic-based nurses. Nurses described low indices of suspicion, prioritization of seemingly more urgent ailments and clinic operational challenges as barriers to TB screening and testing. To improve TB screening and testing in clinics, standard patients should be used to identify real-time factors that impact nurses' clinical decision-making and engage in real-time feedback and discussion with nurses to help optimize opportunities for TB screening and testing.

Les occasions manquées de dépistage de la TB et/ou de tests passifs dans les cliniques continuent de contribuer au nombre de cas manqués. Pour comprendre les raisons de ces occasions manquées, nous avons organisé des discussions de groupe avec des infirmières travaillant dans des cliniques. Les infirmières ont décrit les faibles indices de suspicion, la priorité accordée à des affections apparemment plus urgentes et les défis opérationnels des cliniques comme des obstacles au dépistage de la TB. Pour améliorer le dépistage et le test de la TB dans les cliniques, il faudrait utiliser des patients standard pour identifier les facteurs en temps réel qui influent sur la prise de décision clinique des infirmières et engager une rétroaction et une discussion en temps réel avec les infirmières pour aider à optimiser les occasions de dépistage et de test de la TB.

Aetiological testing compared with syndromic management for sexually transmitted infections in HIV-infected pregnant women in South Africa: a non-randomised prospective cohort study.

OBJECTIVE: To measure the frequencies of sexually transmitted infections (STIs) and adverse pregnancy outcomes among women receiving either aetiological testing or syndromic management for STIs. DESIGN: Non-randomised prospective cohort study. SETTING: Primary healthcare facilities in Tshwane, South Africa. POPULATION: HIV-infected pregnant women attending antenatal care services. METHODS: Participants were enrolled to receive aetiological testing using Xpert® CT/NG and Xpert® TV assays or standard syndromic management. Outcome data were collected at the postnatal care visit (≤30 days from delivery) and from maternity records. Enrolment gestational age-adjusted relative risk (aRR) was calculated. MAIN OUTCOME MEASURES: STI prevalence at postnatal visit, and frequency of adverse pregnancy outcomes (preterm birth, low birthweight). RESULTS: We enrolled 841 women. The prevalence of any STI at baseline was 40%; Chlamydia trachomatis 30%, Neisseria gonorrhoeae 5.6%, Trichomonas vaginalis 20%. The prevalence of STIs at postnatal care was lower among those receiving aetiological testing compared with those receiving syndromic management (14% versus 23%; aRR 0.61; 95% CI 0.35-1.05). No difference was observed between study groups for frequency of preterm birth (23% versus 23%; aRR 1.2, 95% CI 0.81-1.8) and low birth weight (15% versus 13%; aRR 1.1, 95% CI 0.66-1.7). CONCLUSIONS: Aetiological testing provides an effective intervention to reduce the high burden of STIs in pregnant women in South Africa; however, the optimal implementation strategy remains to be determined. TWEETABLE ABSTRACT: Aetiological testing effectively reduces the burden of sexually transmitted infections in pregnancy.

Acceptability and Feasibility of Integrating Point-of-Care Diagnostic Testing of Sexually Transmitted Infections into a South African Antenatal Care Program for HIV-Infected Pregnant Women.

Background: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections may increase the risk of vertical transmission of the human immunodeficiency virus (HIV). In resource-limited settings, symptomatic screening, and syndromic management of sexually transmitted infections (STIs) during pregnancy continue to be the standard of care. In the absence of diagnostic testing, asymptomatic infections in pregnant women go untreated. Objective: To describe the acceptability and feasibility of integrating diagnostic STI screening into first antenatal care visits for HIV-infected pregnant women. Methods: HIV-infected pregnant women were recruited during their first antenatal care visit from three antenatal care clinics in Tshwane District, South Africa, between June 2016 and October 2017. Self-collected vaginal swabs were used to screen for CT, NG, and TV with a diagnostic point-of-care (POC) nucleic acid amplification test. Those with STIs were provided treatment per South African national guidelines. Results: Of 442 eligible women, 430 (97.3%) agreed to participate and were tested. Of those with a positive STI test result (n = 173; 40.2%), 159 (91.9%) received same-day results and treatment; 100% of STI-infected women were treated within seven days. Conclusions: Integration of POC diagnostic STI screening into first-visit antenatal care services was feasible and highly acceptable for HIV-infected pregnant women.

Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

INTRODUCTION: Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end-pRoducts in patients with peripheral arTery disEase and abdominal aoRtic aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. METHODS AND ANALYSIS: This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. TRIAL REGISTRATION NUMBER: trialregister.nl NTR 5363.

Optical and radiometric models of the NOMAD instrument part II: the infrared channels - SO and LNO.

NOMAD is a suite of three spectrometers that will be launched in 2016 as part of the joint ESA-Roscosmos ExoMars Trace Gas Orbiter mission. The instrument contains three channels that cover the IR and UV spectral ranges and can perform solar occultation, nadir and limb observations, to detect and map a wide variety of Martian atmospheric gases and trace species. Part I of this work described the models of the UVIS channel; in this second part, we present the optical models representing the two IR channels, SO (Solar Occultation) and LNO (Limb, Nadir and Occultation), and use them to determine signal to noise ratios (SNRs) for many expected observational cases. In solar occultation mode, both the SO and LNO channel exhibit very high SNRs >5000. SNRs of around 100 were found for the LNO channel in nadir mode, depending on the atmospheric conditions, Martian surface properties, and observation geometry.

Survival outcomes in patients with advanced non-small cell lung cancer treated with erlotinib: expanded access programme data from Belgium (the TRUST study).

Erlotinib has been shown to prolong progression-free (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). We report here on effectiveness data on the subsample of 261 patients from 40 centres in Belgium involved in the TRUST study. Median age was 63 years. Most (69.0%) were male and current/former smokers (84.7%); with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (74.3%), stage IV disease (75.1%) and adenocarcinoma by histology (54.0%). Erlotinib was administered mainly as second- (47.1%) or third-line treatment (48.3%). Response rate was 6.5%; disease control rate 58.3%. Median PFS was 2.2 months. Better PS (P = 0.0384), stage IIIB disease (P = 0.0018) and presence of rash (P < 0.0001) were associated with longer PFS. OS rates at 1, 2 and 3 years were 26.4%, 10.9% and 6.4% respectively. Median OS was 5.9 months. Female gender (P = 0.007), better PS (P < 0.0001), stage IIIB disease (P = 0.0355) and presence of rash (P < 0.0001) were associated with longer OS. The findings confirm the therapeutic benefit of erlotinib in a broad range of patients in a sample from a country with a historically high lung cancer morbidity and mortality burden. Several determinants of PFS and OS are identified.

Genetic linkage map for Amylostereum areolatum reveals an association between vegetative growth and sexual and self-recognition.

Amylostereum areolatum is a filamentous fungus that grows through tip extension, branching and hyphal fusion. In the homokaryotic phase, the hyphae of different individuals are capable of fusing followed by heterokaryon formation, only if they have dissimilar allelic specificities at their mating-type (mat) loci. In turn, hyphal fusion between heterokaryons persists only when they share the same alleles at all of their heterokaryon incompatibility (het) loci. In this study we present the first genetic linkage map for A. areolatum, onto which the mat and het loci, as well as quantitative trait loci (QTLs) for mycelial growth rate are mapped. The recognition loci (mat-A and het-A) are positioned near QTLs associated with mycelial growth, suggesting that the genetic determinants influencing recognition and growth rate in A. areolatum are closely associated. This was confirmed when isolates associated with specific mat and het loci displayed significantly different mycelial growth rates. Although the link between growth and sexual recognition has previously been observed in other fungi, this is the first time that an association between growth and self-recognition has been shown.

Complete genetic linkage maps from an interspecific cross between Fusarium circinatum and Fusarium subglutinans.

The Gibberella fujikuroi complex includes many plant pathogens of agricultural crops and trees, all of which have anamorphs assigned to the genus Fusarium. In this study, an interspecific hybrid cross between Gibberella circinata and Gibberella subglutinans was used to compile a genetic linkage map. A framework map was constructed using a total of 578 AFLP markers together with the mating type (MAT-1 and MAT-2) genes and the histone (H3) gene. Twelve major linkage groups were identified (n=12). Fifty percent of the markers showed significant deviation from the expected 1:1 transmission ratio in a haploid F(1) cross (P <0.05). The transmission of the markers on the linkage map was biased towards alleles of the G. subglutinans parent, with an estimated 60% of the genome of F(1) individuals contributed by this parent. This map will serve as a powerful tool to study the genetic architecture of interspecific differentiation and pathogenicity in the two parental genomes.

Immunoblotting, ELISA and culture evidence for Chlamydiaceae in sows on 258 Belgian farms.

The prevalence of Chlamydiaceae infections on 258 closed pig breeding farms in Belgium was examined. For this purpose, 258 farms were randomly selected in the provinces West-Vlaanderen (44%), Oost-Vlaanderen (20%), Antwerpen (10%) and Vlaams-Brabant (6%). Of all farms examined, 96.5% were positive for Chlamydia-specific antibodies in ELISA and most were moderately to strongly positive. ELISA results revealed only 9 (3.5%) sero-negative farms. None of the ELISA negative sera reacted in immunoblotting. Only 212 of 249 ELISA positive sera reacted positive in immunoblotting. Additionally, 23 autopsy samples were examined by isolation in Vero cells. The major outer membrane sequence of the one isolate obtained showed 98.6% amino acid homology to the one of Chlamydophila psittaci strain CP3, formerly isolated from a pigeon. Present observations indicate that chlamydial infections are nearly endemic in the Belgian pig population and that Belgian pigs can become infected with C. psittaci. Nevertheless, the role and significance of Chlamydiaceae as pathogens in pigs remain unsolved and require further investigation.

Submicroscopic anatomy of photoreceptors in the female scale insect Eupulvinaria hydrangeae (Homopteres, Coccideae).

The submicroscopic anatomy of the eye in female Eupulvinaria is described. This scale insect has no compound eyes but simple pericerebral eyes composed of one pair of ocelli. The ocelli, located dorsolaterally to the brain, are of rhabdomeric type. They are situated in the subepidermal region underneath the basement membrane of the epidermis. Each ocellus consists of a cup made of a layer of numerous pigmented cells enclosing a few photoreceptive cells. The cuticular lens is facing the opening of the pigment-cup, while the optic nerve is emerging from the bottom of the cup. Pigmented cells show characteristic pigment granules. They are linked to each other by interdigitations or by desmosomes junctions. Both dendrites and cell body of the photoreceptor cell lie inside the eyecup, while the axon lies outside. The dendritic processes consist of large shaft-shaped rhabdomeres with microvilli extending perpendicular to the direction of the shaft. These microvilli are enveloped by digitiform cytoplasmic extensions of pigmented cells. These latter strands are free of pigment granules but contain microtubules orientated to the centre of the cup.

Detection and quantification of ATP and heavy metal with electronical micro-circuits.

In order to use whole eukaryotic cells as an active element in the detection and amplification of biological signals, for both in vitro and in vivo applications, we have undertaken a first approach to interface live cells and integrated circuit, and evaluate the possibility to develop a microbioreactor. An amplified photodiode system was designed and built as an electronical circuit in a way that it could easily be miniaturised. In parallel micro-chips with silicium chambers were used as microbioreactors to adhere cells. We showed here that this etched silicon chamber allows endothelial and CHO cells spreading, permitting determination of a number of cell properties {\it on line} providing appropriate integrated circuits are designed to perform the desired functions. The photodiode system reacting to the luminescent luciferase system permitted, through the use of appropriate software from a personal computer (PC) connected on line in vitro, the determination of ATP concentration, and using different luciferase transfected bacteria permitted the detection of constitutive or induced luminescence.

Trypanosoma cruzi infects human dendritic cells and prevents their maturation: inhibition of cytokines, HLA-DR, and costimulatory molecules.

Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas' disease. Despite the many immune system disorders recognized in this infection and the crucial role played by dendritic cells (DC) in acquired immune responses, it was not known whether these cells could be infected by T. cruzi trypomastigotes and the consequences of such an infection on their immune functions. We now provide evidence that human monocyte-derived DC can be infected by T. cruzi and can support its intracellular multiplication. Interestingly, this infection has functional consequences on immature DC and on their maturation induced by lipopolysaccharide (LPS). First, after T. cruzi infection, the basal synthesis of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) was impaired. Furthermore, the process of maturation of DC induced by LPS was drastically affected by T. cruzi infection. Indeed, secretion of cytokines such as IL-12, TNF-alpha, and IL-6, which are released normally at high levels by LPS-activated DC, as well as the up-regulation of HLA-DR and CD40 molecules, was significantly reduced after this infection. The same effects could be induced by T. cruzi-conditioned medium, indicating that at least these inhibitory effects were mediated by soluble factors released by T. cruzi. Taken together, these results provide new insights into a novel efficient mechanism, directly involving the alteration of DC function, which might be used by T. cruzi to escape the host immune responses in Chagas' disease and thus might favor persistent infection.

Cranio-facial dysmorphism: experimental study in the mouse, clinical applications.

To obtain a better understanding of mandibulo-facial dysostosis and hemicraniofacial microsomia in man, the authors carried out a histologic and scanning electron microscope study of the facial malformations produced in mouse embryos by retinoic acid and methyl-triazene. The administration of 400 mg/kg 13 cis-retinoic acid (RA) to pregnant C57BL mice on day 9 of gestation produced anomalies of the cephalic extremity in the embryos resembling human mandibulo-facial dysostosis. The 64 embryos collected presented hypoplasia of the branchial arches or the snout in 79% of cases, auricular anomalies in 47% and ophthalmic anomalies in 12.5%. Fourteen NMRI mice on day 10.5 of gestation were treated with 1.5 mg (0.5 mg/kg) methyl-triazene (Methyl). The 126 embryos collected had developed a very high percentage of micromandibles and anomalies of both embryonic ears (94.6% to 100%). Finally, although the facial anomalies produced by retinoic acid resemble the human mandibulo-facial dysostosis syndrome, no correlation was found between hemicraniofacial microsomia and the administration of methyl-triazene.

Effects of irradiation on facial development in mouse embryos.

The purpose of this study was to observe the effects of irradiation on the craniofacial development of NMRI mouse embryos. Two populations of pregnant mice were irradiated with a single dose of 2 Gray on day 8 of gestation for the first population (Po. 1) and on day 9 of gestation for the second population (Po. 2). On gestational days 9 to 17, embryos were submitted to histological and scanning electron microscope examinations. The two populations of embryos presented a high percentage of centro-facial hypoplasia (74.7% for Po. 1 and 75% for Po. 2) which was more pronounced in the latter one. Ocular anomalies were present in 16% of the first population. Cases of anencephaly, cleft palate and anomalies of the central nervous system were found in both populations.

Alpha-particle radiotherapy with 211At-labeled monodisperse polymer particles, 211At-labeled IgG proteins, and free 211At in a murine intraperitoneal tumor model.

Four different chemical forms of the alpha-particle emitting radionuclide 211At were injected intraperitoneally in mice inoculated intraperitoneally 30 hr in advance with 10(6) cells of the K13 murine hybridoma cell line. The different 211At forms were (a) free 211At, (b) 211At-labeled TP-3 nonspecific monoclonal antibody (211At-TP-3), (c) 211At-labeled human IgG kappa (211At-hIgG kappa), and (d) 211At-labeled monodisperse polymer particles (211At-MDPP). A significantly prolonged survival (P < 0.05) was observed with injected doses down to 7 kBq for the 211At-MDPP, and down to 25 kBq for 211At-hIgG kappa. There were no significant differences in survival between 211At-MDPP, 211At-hIgG kappa, and 211At-TP-3 at the dose level of 200 kBq. The group receiving 250 kBq free 211At per animal had a shorter survival than the three other forms at 200 kBq. The groups treated with 500, 200, and 65 kBq 211At-MDPP had a similar survival. The group given the highest dose of 211At-hIgG kappa (275 kBq) had the highest fraction (50%) of long-term survivors of all groups. Biodistribution measurements and total body scintigrams in mice without tumor revealed that the free 211At was distributed all over the body within 10 min after injection while at 2 hr a high fraction of the 211At-TP-3 and 211At-hIgG kappa was still present intraperitoneally. In conclusion this study indicates that 211At-labeled MDPP and 211At-labeled IgG's may be efficient tools for treatment of intraperitoneal superficial tumor cells and malignant ascites.

[Surgical revision for otospongiosis]. / Révision chirurgicale pour otospongiose.

Revision surgery for otosclerosis is analysed in 26 patients. Audiometric results are better in patients with recurrent rather than persistent transmission hearing loss. Total platinectomy with interposition may be a solution for patients with chronic tubal dysfunction.

Analysis of prognostic factors in stage I epithelial ovarian carcinoma: importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse.

OBJECTIVES: Our purpose was to identify prognostic factors in stage I epithelial invasive ovarian carcinoma. STUDY DESIGN: The traditional clinical and pathologic prognostic variables and deoxyribonucleic acid ploidy were analyzed in a group of 290 patients. RESULTS: A multivariate analysis identified degree of differentiation as the most powerful prognostic indicator of disease-free survival, followed by deoxyribonucleic acid ploidy and, finally, International Federation of Gynecology and Obstetrics (1986) stage. Tumors with clear cell carcinoma elements were not graded, and in this subgroup International Federation of Gynecology and Obstetrics (1986) stage was the most important prognostic characteristic. When the effects of the three most important factors were accounted for in graded tumors, then none of the following were prognostic: histologic type, dense adhesion, extracapsular growth, ascites, rupture during surgery, International Federation of Gynecology and Obstetrics (1973) stage, size of tumor, and age and type of adjuvant treatment. None of 77 patients with well differentiated deoxyribonucleic acid diploid tumors had relapses. CONCLUSION: Deoxyribonucleic acid ploidy is an important new independent prognostic factor in stage I ovarian carcinoma.

Intraperitoneal radioactive phosphorus therapy in ovarian carcinoma. Analysis of 313 patients treated primarily or at second-look laparotomy.

BACKGROUND: Intraperitoneal radioactive phosphorus (phosphorus-32) has been used in ovarian cancer during the last three decades. In the current study, the survival results, the patterns of recurrence, morbidity rates, and phosphorus-32 distribution scintigrams were reviewed in 313 patients treated with phosphorus-32 colloid. METHODS: Between July 1982 and July 1988, 245 patients with epithelial ovarian carcinoma were treated with phosphorus-32 as primary adjuvant treatment; 59 patients received phosphorus-32 as consolidating therapy after negative results during second-look surgery and 9, after positive findings during second-look laparotomy. Fifty patients with negative second-look findings were assigned randomly to receive phosphorus-32 or no treatment. The phosphorus-32 distribution was studied by scintigraphic imaging in 297 patients. RESULTS: The actuarial 5-year crude survival rate was 81% in the group treated with phosphorus-32 adjuvantly and 79% in the group treated after second-look surgery. Crude and disease-free survival rates were similar in both groups randomized at second-look surgery to receive either phosphorus-32 or no treatment. Phosphorus-32 scintigraphy showed major isotopic accumulations in 48 (16%) patients. There were two deaths (0.6%), which, at least partly, could be attributed to the phosphorus-32 treatment. Small bowel obstruction without tumor recurrence occurred in 22 (7%) patients (13 treated surgically and 9 medically) and was not related to any patient characteristic, including phosphorus-32 distribution. CONCLUSIONS: Phosphorus-32 therapy was associated with a considerable number of bowel complications. The occurrence of small bowel obstruction could not be predicted by any patient characteristic. Without an untreated observation group, the authors were unsure whether adjuvant phosphorus-32 treatment conferred a survival advantage.