People living with HIV and procreation: 30 years of progress from prohibition to freedom?

The emergence of human immunodeficiency virus (HIV) infection in the 1980s drastically changed the prospects of conceiving a child for the man or woman infected with the virus. Advances in treatment then made it possible to envisage pregnancy while decreasing the risk of transmission to the child when the mother was infected. For couples where one partner was HIV-positive and who desired a child, recourse to medical help, notably medically assisted procreation, was discouraged, and very few centres offered such assistance in the 1980s and 1990s. Improved knowledge of viral excretion in the genital tracts, together with more effective treatment, made it possible to envisage medically assisted procreation for these couples, allowing them to have a child while at the same time likely reducing the risk of transmitting HIV to their partner. Several programmes have demonstrated their effectiveness in this domain. Owing to continually increasing knowledge over the past decade, natural conception can now be proposed. Couples where one or both partners are HIV-positive may opt for medically assisted procreation or natural reproduction. Specialists in reproductive medicine and HIV specialists need to provide couples with objective information allowing them to achieve near-optimal conditions that minimize HIV transmission risk. Couples will then be able to choose freely the mode of procreation most appropriate for them.

Involvement and alteration of the Sonic Hedgehog pathway is associated with decreased cholesterol level in trisomy 18 and SLO amniocytes.

BACKGROUND: Trisomy 18 and Smith-Lemli-Opitz syndrome are two polymalformative conditions in which a cholesterol defect has been noted. When they occur prenatally, they are associated with a decreased maternal unconjugated estriol (uE(3)) level. Cholesterol plays an essential role in the Sonic Hedgehog pathway, allowing Shh protein maturation leading to its maximal activity. Many malformations in these two syndromes occur in Shh dependent tissues. We thus sought to assess whether a cholesterol defect could affect the Shh pathway and explain some of the observed malformations. MATERIALS AND METHODS: We selected 14 cases of trisomy 18 and 3 cases of SLO in which the maternal uE(3) level was decreased and reported malformations were observed after fetopathological examination. We correlated the number of malformations with maternal uE(3) level. We then carried out cholesterol concentrations in separate culture media consisting of trisomy 18, SLO and control amniocytes. Finally, we analyzed the Shh pathway by testing the gene expression of several Shh components: GLI transcription factors, BMP2, BMP4, TGFß1, COL1A1 and COL1A2. RESULTS AND DISCUSSION: There was an inverse correlation between phenotypic severity and maternal uE(3) levels in SLO and trisomy 18. The cholesterol levels in the amniocyte culture media were correlated with maternal uE3 levels and were significantly lower in T18 and SLO amniocytes, reflecting cholesterol defects. There was an alteration in the Shh pathway since expression of several genes was decreased in T18 and SLO amniocytes. However, these cholesterol defects were not solely responsible for the altered Shh pathway and the malformations observed.

[Management of an HTLV-1 infected man in assisted reproductive technology]. / Prise en charge en assistance médicale à la procréation d'un patient infecté par HTLV-1.

Management of people infected by HTLV-1 in assisted reproductive technology (ART) is a rare event. Since HTLV is sexually transmitted, HTLV serodiscordant couples have to systematically use condoms. The sperm processing (centrifugation on density gradient) performed for semen of HIV-infected men was applied. Detection of HTLV-1 provirus DNA was negative before and after sperm processing, allowing ART.

[How a self-managed team can improve cohesion and communication during the patient's journey in a radiotherapy department: Experience of centre Jean-Bernard (Le Mans, France)]. / Comment une équipe autonome peut améliorer la cohésion et la communication autour de la prise en charge du patient en radiothérapie : expérience du centre Jean-Bernard.

Efficient communication between professionals is of upmost importance in improving treatment safety in a radiotherapy department, and is also necessary to enhance the quality of work life. Taking as example the organizations in industry, a self-managed team centred on patients with head and neck cancers treated with radiation has been implemented in 2018 in centre Jean-Bernard (Le Mans, France). After over a year's experience, a real benefice has been found and validates the plan to extend this model to other departments.

Biological data integration using Semantic Web technologies.

Current research in biology heavily depends on the availability and efficient use of information. In order to build new knowledge, various sources of biological data must often be combined. Semantic Web technologies, which provide a common framework allowing data to be shared and reused between applications, can be applied to the management of disseminated biological data. However, due to some specificities of biological data, the application of these technologies to life science constitutes a real challenge. Through a use case of biological data integration, we show in this paper that current Semantic Web technologies start to become mature and can be applied for the development of large applications. However, in order to get the best from these technologies, improvements are needed both at the level of tool performance and knowledge modeling.

[Acute-placental dysfunction by villous-maturation defect and late-fetal mortality]. / Dysfonction placentaire aiguë par retard de maturation villositaire et décès foetal tardif.

INTRODUCTION: The placental histological examination is essential in the assessment of stillbirths, especially those of third trimester, which are often of placental origin by chronic placental dysfunction and sometimes by acute dysfunction. The physiopathogenesis of the latter remains obscure. MATERIAL AND METHOD: Three stillbirths, one per partum and two after 38 and 39 weeks gestation, caused by acute-placental dysfunction by villous maturation defect were studied. The maternal aetiological investigations and the fetal autopsies were normal. Placentas were pale. Villi were numerous, normal size but fibrous, showing a severely reduced vascularization and a lack of syncytium-capillary membranes. RESULTS: Only one author studied the villous maturation defect. He defines this entity by the same characteristics as that noted in our observations. Its incidence would be of 5.7% and would be associated with fetal death only after the eighth month in 2.3 % of cases, with a risk of recurrence estimated at 10%. CONCLUSION: This entity, probably underestimated, must be indexed systematically in any late fetal death and any unexplained per partum asphyxia, in order to help the couple overcome a fetal death and to give doctors a medicolegal support.

[Uterine and ovarian necrosis following embolisation of the uterine arteries for postpartum haemorrhagia]. / Nécrose utérine et ovarienne après embolisation des artères utérines pour hémorragie de la délivrance.

We report here the case of a young woman who presented with pain, fever and apparent cutaneous sub ischaemia following embolisation of the uterine arteries for postpartum haemorrhagia. This embolisation was carried out by bilateral selective catheterism of the uterine arteries using 45 to 150 micron polyvinyl alcohol particles. Investigative laparotomy was decided in view of the persistence of the symptoms, and the patient underwent hysterectomy with ablation of the right adnexa to treat uterine necrosis and adnexal atrophy. Because of the information that we have actually, we can explain that this complication is linked with the use of polyvinyl alcohol small size particles. The migration of those embolisation agents might be responsible for obliteration of a large number of distal vessels. Those embolisation agents must, because of recommendation for good practice published in 2004, be reserved to exceptional cases to minimize the complication of embolisation.

Practice of pathological examinations in stillbirths: A 10-year retrospective study.

OBJECTIVES: To describe the practice of fetal and placental pathological examinations in a large series of spontaneous stillbirths over 10 years. MATERIALS AND METHODS: Inclusion of cases recorded by the Lower Normandy Regional Fetal-Infant Mortality Observatory (observatoire régional de mortalité fœto-infantile) from January 1, 2005 to December 31, 2014. The possible cause of death was coded in accordance with the ReCoDe classification system. RESULTS: Seven hundred and forty-four cases were recorded. The placental examinations were conducted in 93.7% of cases (CI95%[91.7-95.3]), increasing over the study period, and an autopsy was proposed in 87.2% of cases (CI95%[84.8-89.6]). Autopsy was conducted less frequently during the most recent period, with parental refusal increasing over time. In multivariate analysis, no factor was associated with a higher frequency of placental examinations, while autopsy was proposed more often under certain circumstances: less than 4 pregnancies (P<10-2), birth weight from 1000 to 1500 grams (P=0.05), singleton (P<10-2), clinical context not suggesting a cause (P<10-3), type 1 or 2 maternity ward (P<10-2), antepartum death (P<10-3). CONCLUSION: Placental analysis was almost systematically realized, as suggested by international guidelines. Fetal autopsy was often performed, however only in some specific circumstances. New practice guidance to realize customized fetal autopsies appear to be necessary.

Detection and quantification of HIV-1 RNA with a fully automated transcription-mediated-amplification assay.

BACKGROUND: Nucleic acid testing is the major method used to monitor HIV viral load. Commercial systems based on real-time PCR assays are available for high-volume centralized laboratory testing, but they are not fully automated. OBJECTIVES AND STUDY DESIGN: We have compared the diagnostic performance of the Hologic Aptima HIV-1 Quant Dx assay (Aptima) (based on real-time TMA) on the Panther instrument, a fully-automated random access platform, to that of, the Roche Cobas Ampliprep Cobas TaqMan (CAP/CTM) HIV-1 version 2.0 (based on real-time PCR). RESULTS: Probit analysis of replicate dilutions of NIBSC WHO International HIV-1 Standard, gave LODs of 8.6 c/ml for Aptima and 15.2 c/ml for CAP/CTM. The agreement between the assays was excellent when measuring HIV RNA in a calibrated reference (κ=0.90, p<0.001) and good when measuring clinical samples (κ=0.62, p<0.001). The correlation among the samples quantified by the two methods was very good (r=0.95, p<0.001) and the mean difference between the values obtained with the two assays was 0.02 log c/ml for B and non-B subtypes. The vast majority of results showed <0.5 log variance between the two assays (89%); only one sample showed results that differed by over 1.0 log c/ml. CONCLUSION: The performance of the new fully automated Aptima assay is adequate for clinical monitoring of HIV-1 RNA during infections and treatment. The Aptima assay is well suited for routine laboratory use.

A Review of Numerical Simulation and Analytical Modeling for Medical Devices Safety in MRI.

OBJECTIVES: To review past and present challenges and ongoing trends in numerical simulation for MRI (Magnetic Resonance Imaging) safety evaluation of medical devices. METHODS: A wide literature review on numerical and analytical simulation on simple or complex medical devices in MRI electromagnetic fields shows the evolutions through time and a growing concern for MRI safety over the years. Major issues and achievements are described, as well as current trends and perspectives in this research field. RESULTS: Numerical simulation of medical devices is constantly evolving, supported by calculation methods now well-established. Implants with simple geometry can often be simulated in a computational human model, but one issue remaining today is the experimental validation of these human models. A great concern is to assess RF heating on implants too complex to be traditionally simulated, like pacemaker leads. Thus, ongoing researches focus on alternative hybrids methods, both numerical and experimental, with for example a transfer function method. For the static field and gradient fields, analytical models can be used for dimensioning simple implants shapes, but limited for complex geometries that cannot be studied with simplifying assumptions. CONCLUSIONS: Numerical simulation is an essential tool for MRI safety testing of medical devices. The main issues remain the accuracy of simulations compared to real life and the studies of complex devices; but as the research field is constantly evolving, some promising ideas are now under investigation to take up the challenges.

Facial features in Harlequin ichthyosis: Clinical findings about 4 cases.

We report 4 cases of Harlequin ichthyosis, which is a rare and severe congenital ichthyosis involving the face. Facial appearance consists in severe ectropion, conjonctival edema, eclabium, flattened ears, broadened nose and large, thick, plate-like skin scales. Recent advances in neonatal care have been made, such as retinoid therapy, and have led to an increased survival rate. Early surgical correction of ectropion may be required because of ocular complications.

Oxidative damage to lysozyme by the hydroxyl radical: comparative effects of scavengers.

The hydroxyl radical (OH.) is a highly-damaging reactive oxygen species, given its high reactivity and the consequent generation of secondary free radicals. This study was aimed at determining the qualitative and quantitative aspects of OH. scavenging by pentoxifylline (Ptx, a methylxanthine), uric acid and thymine on the OH.-induced alterations of a protein, lysozyme. Lysozyme was inactivated by OH. with a yield of 6.5 mol OH./mol lysozyme; moreover, SDS-PAGE showed a loss of native lysozyme (14.4 kDa), the presence of dimer and trimer aggregates and characteristic fragmentation. Tryptophan fluorescence was lost before aggregation became detectable in terms of bityrosine formation. Increasing concentrations of OH. scavengers gave increasing protection of lysozyme activity. Although all three compounds scavenge OH. with high rate constants, their effects were different: uric acid and Ptx prevented aggregation and preserved enzyme activity, whereas thymine preserved activity but did not prevent aggregation. These differences appear to be related to the formation of reducing secondary radicals, underlining the importance of this mechanism in the effects of scavengers.

Superoxide anion production in glass-adherent polymorphonuclear leukocytes and its relationship to calcium movement.

The production of superoxide anion (O2-.) was measured in relation to 45Ca movement in glass-adherent polymorphonuclear leukocytes (PMNs), and the results were compared with those obtained by ourselves and others on PMNs in suspension. In adherent PMNs, O2-. production stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was of rapid onset and short duration; this was also true of PMNs in suspension. However, O2-. production was insensitive to the concentration of extracellular calcium. Both in adherent and non-adherent PMNs, O2-. production stimulated with phorbol myristate acetate (PMA) had a latency time and was of long duration. In adherent PMNs, pretreatment with PMA potentiated the FMLP-induced O2-. production by lengthening its duration without changing its initial rate. In adherent PMNs (10(-10)-10(-7) M) FMLP induced a fast but transient dose-dependent increase in 45Ca within 1 min, whereas PMA only released 45Ca about 5 min after its addition to the cell culture medium. Pretreatment of PMNs with 10 or 100 ng/ml PMA for 3 min before stimulation by 10(-7) M FMLP reduced the 45Ca efflux observed with FMLP alone. We conclude that O2-. production by adherent PMNs cannot simply be related to Ca2+ movement. In comparison with non-adherent cells, adherence seemed to interfere with the characteristics of both calcium and O2-. generation, probably by modifying the cytoskeleton.

Myocardial neutrophil sequestration and activation related to the reperfusion of human heart during coronary artery surgery.

OBJECTIVE: The aim was to determine if neutrophils are activated and sequestered as they pass through postischaemic human myocardium. METHODS: The occurrence of neutrophil activation during the reperfusion of the ischaemic myocardium was investigated in 16 selected patients undergoing coronary artery bypass surgery. Neutrophils were counted and elastase and lactoferrin released into the plasma were measured simultaneously in myocardial venous blood and in peripheral venous blood, before aortic cross clamping (T0), and two (T1), 10 (T2), and 20 (T3) min after unclamping. RESULTS: At T0, no statistically significant difference was noted between peripheral and myocardial blood with respect to the three variables studied. Reperfusion was associated with a significantly lower neutrophil count in myocardial blood compared to peripheral blood (p < 0.001), suggesting that neutrophils were trapped within the myocardium during reperfusion. In addition, levels of elastase (T1, T2, and T3), and lactoferrin (T1) were significantly higher in myocardial blood as compared to peripheral blood (p < 0.001), suggesting that activated neutrophils released their granular content into the plasma milieu. CONCLUSION: We provide evidence consistent with local neutrophil activation during myocardial reperfusion in patients undergoing coronary artery bypass surgery, in addition to the well described systemic activation related to cardiopulmonary bypass.

[Osteoid osteoma on distal phalanx tip of second toe, without scintigraphy fixation]. / Ostéome ostéoïde de la phalange distale sans hyperfixation scintigraphique.

Osteoid osteoma is a very small painful, benign tumor, located preferentially on long bones. Cases on the phalanxes of the toes are very rare. Pain takes up nearly all the clinical presentation. Poor clinical signs and atypical location make diagnosis difficult and delayed. Sometimes, it can be confused with local infection. Various additional tests are described to help diagnosis. Technetium 99-m scintigraphy coupled with CT is the key exam with high sensitivity and morphological accuracy. We report on the case of a 10-year-old boy with an atypical location of osteoid osteoma on the distal phalanx tip of the second toe, without scintigraphy fixation and obvious nidus on X-ray and CT scan.

[Alveolar capillary dysplasia with misalignment of pulmonary veins: a fatal cause of refractory neonatal cyanosis]. / Dysplasie alvéolo-capillaire avec mésalignement des veines pulmonaires : une cause de cyanose néonatale réfractaire létale.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare neonatal pathology that combines refractory hypoxemia with severe pulmonary arterial hypertension, and leads to death every time. Histologic examination of lung tissue confirms the diagnosis and is characterized by a decreased number of pulmonary capillaries, immature lobular development, and abnormal proximity between pulmonary arteries and veins. This abnormal proximity is responsible for an arteriovenous shunt. We report five cases confirmed by postmortem histology, which occurred over 14 years in Lower Normandy (France). The cumulative incidence is therefore of 1.8 for 100,000 births. In these five cases, the first symptoms appeared during the first hour of life and death occurred before 24h in four of five cases. The patient with the longest survival had mild histological lesions and delayed emergence of the first symptoms. Genitourinary and gastrointestinal anomalies were associated with ACD/MPV in two cases, and bilateral pulmonary hypoplasia in three cases. Optimized invasive ventilation, pulmonary vasodilators, vasoactive drugs, and pulmonary surfactant did not improve survival. Extracorporeal membrane oxygenation (ECMO) was not used. We present a review of the literature on ACD/MPV, a clinical and histological entity little known to both clinicians and pathologists, whereas a premortem diagnosis is possible and genetic counseling in affected families can be suggested.

Memristive and neuromorphic behavior in a Li(x)CoO2 nanobattery.

The phenomenon of resistive switching (RS), which was initially linked to non-volatile resistive memory applications, has recently also been associated with the concept of memristors, whose adjustable multilevel resistance characteristics open up unforeseen perspectives in cognitive computing. Herein, we demonstrate that the resistance states of Li(x)CoO2 thin film-based metal-insulator-metal (MIM) solid-state cells can be tuned by sequential programming voltage pulses, and that these resistance states are dramatically dependent on the pulses input rate, hence emulating biological synapse plasticity. In addition, we identify the underlying electrochemical processes of RS in our MIM cells, which also reveal a nanobattery-like behavior, leading to the generation of electrical signals that bring an unprecedented new dimension to the connection between memristors and neuromorphic systems. Therefore, these LixCoO2-based MIM devices allow for a combination of possibilities, offering new perspectives of usage in nanoelectronics and bio-inspired neuromorphic circuits.

Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children.

BACKGROUND: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected. PATIENTS: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV. METHODS: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation. RESULTS: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions. CONCLUSIONS: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.

Shift in HIV resistance genotype after treatment interruption and short-term antiviral effect following a new salvage regimen.

OBJECTIVE: To investigate the changes in genotypic drug-resistance pattern, plasma HIV RNA and CD4 cell count after treatment interruption and assess the short-term antiviral effect of a new salvage regimen. DESIGN: Prospective study of 38 patients with multiple failing regimens who had completely stopped all medication for 3 months before a three to five-drug regimen was reintroduced according to clinical guidelines. METHODS: Patients were tested for HIV resistance before and after treatment interruption by population-based sequencing and clonal analysis of selected patients. RESULTS: Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 0.4 log10 and a median decrease in CD4 cell count of 43 x 10(6)/l. Sixty-one per cent of patients had a shift from the drug-resistant genotype to a predominantly wild-type genotype. The patients significantly likely to show genotype reversion were those in Centers for Disease Control groups A or B, who had been exposed to few drugs, had a low plasma HIV RNA, or a high CD4 cell count. The only independent factor predicting genotype reversion was the clinical stage. The median change in plasma HIV RNA at month 3 after treatment reintroduction was -2.3 log10 copies/ml in patients who had genotype reversion compared with -0.6 log10 copies/ml in patients without genotype reversion (P = 0.004). CONCLUSION: Suspending treatment for 3 months after multiple failures could be a suitable strategy for optimizing salvage therapy provided it is instituted early, before the HIV disease becomes too advanced.