Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Functional balance between neuraminidase and haemagglutinin in influenza viruses.

Seasonal influenza A and B viruses are important human pathogens responsible for significant morbidity and mortality worldwide. In addition, influenza A zoonotic viruses are a constant pandemic threat. These viruses present two major surface glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). These two glycoproteins both recognize the sialic acid and have complementary activities, the HA binds the sialic acid through its receptor-binding site, the NA is a receptor-destroying enzyme that cleaves α2-3 and α2-6-linked sialic acids. Therefore, the functional HA/NA balance is a critical factor for a good viral fitness and plays a major role in overcoming the host barrier and the efficiency of sustained human-to-human transmission. Although the two glycoproteins are in constant evolution, the HA/NA balance seems to remain stable in human viruses because an optimal balance is required to maintain good viral fitness. Understanding the evolution of influenza viruses requires an in-depth exploration of the HA/NA balance.

Note: A large open ratio, time, and position sensitive detector for time of flight measurements in UHV.

We report on the construction of an UHV compatible 40 mm active diameter detector based on micro channel plates and assembled directly on the feed-throughs of a DN63CF flange. It is based on the charge division technique and uses a standard 2 inch Si wafer as a collector. The front end electronic is placed directly on the air side of the flange allowing excellent immunity to noise and a very good timing signal with reduced ringing. The important aberrations are corrected empirically providing an absolute positioning accuracy of 500 µm while a 150 µm resolution is measured in the center.

Nuclear envelope-related lipodystrophies.

Several alterations in nuclear envelope proteins building up the lamina meshwork beneath the inner nuclear membrane (mutations in lamins A/C, alterations of prelamin-A maturation, lamin B mutations or deregulation) have been shown to be responsible for or associated to human lipodystrophic syndromes. Lipodystrophic syndromes are rare and heterogeneous diseases, either genetic or acquired, characterized by generalized or partial fat atrophy associated with metabolic complications comprising insulin-resistant diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Recent advances in the molecular genetics of different types of lipodystrophies generally pointed to primary adipocyte alterations leading to impaired adipogenesis and/or deregulation of the adipocyte lipid droplet. However, the precise mechanisms linking nuclear envelope abnormalities to lipodystrophies remain largely unknown. The phenotype of nuclear envelope-linked lipodystrophies ranges from the typical familial partial lipodystrophy of the Dunnigan type (FPLD2), due to heterozygous substitutions of the 482nd arginine of lamins A/C, to complex diseases that can combine lipodystrophy, metabolic complications, muscular or cardiac alterations and/or signs of accelerated aging. In this review we present the clinical, tissular and cellular characteristics of the nuclear envelope-linked lipodystrophies, as well as their hypothetical pathophysiological mechanisms.

Long-term outcomes in adolescents perinatally infected with HIV-1 and followed up since birth in the French perinatal cohort (EPF/ANRS CO10).

BACKGROUND. Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV) are reaching adolescence, largely because of advances in treatment over the past 10 years, but little is known about their current health status. We describe here the living conditions and clinical and immunovirologic outcomes at last evaluation among this pioneering generation of adolescents who were born before the introduction of prophylaxis for vertical transmission and whose infections were diagnosed at a time when treatment options were limited. METHODS. The eligible population consisted of HIV-1-infected children who were born before December 1993 and who were included at birth in the prospective national French Perinatal Cohort (EPF/ANRS CO10). RESULTS. Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2 nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated. The median CD4 cell count was 557 cells/microL, and 200 cells/microL was exceeded in 94% of patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass index were similar to French reference values for age, and school achievement was similar to nationwide statistics. Better immunologic status was associated with being younger and with having begun HAART earlier. Undetectable viral load was associated with maternal geographic origin and current HAART. CONCLUSIONS. Given the limited therapeutic options available during the early years of these patients' lives and the challenge presented by treatment adherence during adolescence, the long-term outcomes among this population are encouraging.

[Efficacy of botulinum toxin A in the treatment of axillary and palmar hyperhidrosis: 10 cases]. / Efficacité de la toxine botulique A dans le traitement de l'hyperhidrose axillaire et palmaire: 10 cas.

UNLABELLED: Axilliary and palmar hyperhidrosis can become a considerable social and psychological handicap. Local treatments are not always effective and endoscopic thoracic sympathectomy is not without side effects. The efficacy of botulinum toxin has recently been demonstrated in axillary and palmar hyperhidrosis. Between June 2001 and June 2002, we treated all the patients presenting with axillary and palmar hyperhidrosis, resistant to classical treatments, with intradermal injections of botulinum toxin A (Dysport). The aim was to assess the interest of this technique at moderate doses, in a prospective, open, controlled study. PATIENTS AND METHODS: The hyperhidrotic areas, revealed by Minor's test, were treated with intradermal injections of 100 U of Dysport in the axilliary form and 250 U in the palmar form. Patients were seen after 1 month and 6 months and underwent a Minor's test, photographic control and they filled-in a questionnaire to measure their satisfaction. RESULTS: Ten patients: 9 women and 1 man aged 19 to 63, were included. Three of them consulted for palmar hyperhidrosis and 7 for auxiliary hyperhidrosis. Within 2 to 7 days, treatment was successful in all patients. The follow-up was of 3 to 12 months. The satisfaction index was comprised between 7/10 and 9/10. The relapse-free interval was of 2 to 9 months. Three patients were given a second injection, which doubled the relapse-free period. Side effects included pain with the palmar injections and moderate headaches. DISCUSSION: This French study confirms the efficacy of botulinum toxin A in the treatment of axillary and palmar hyperhidrosis with relatively low doses (100 U of Dysport per armpit and 250 U per palm). This is an easily reproducible, well tolerated, method without major side effects.

HLA-G and NK receptor are expressed in psoriatic skin: a possible pathway for regulating infiltrating T cells?

Recent data have suggested that in psoriasis, the T-infiltrating cells could be submitted to regulatory pathways, possibly through natural killer receptors. HLA-G binds to different natural killer receptors and is able to inhibit T-cell functions. Because this molecule is induced by interferon-gamma, a major cytokine in psoriasis, we asked whether HLA-G and its receptor might be expressed in this disease. Specific RNAs for HLA-G1 and HLA-G5 were consistently found in lesional skin specimens, soluble HLA-G5 transcripts being found only in psoriasis. HLA-G protein was found in all psoriatic sections, but never in normal skin controls. Double labeling demonstrated that HLA-G-positive cells were CD68(+), CD11c(+) macrophages. The NKR ILT2 was also present in psoriatic skin, the T CD4(+)-infiltrating cells expressing indeed ILT2. The demonstration of HLA-G and ILT2 expression in psoriatic skin suggests that this pathway may act as an inhibitory feed back aimed to down-regulate the deleterious effects of T-cell infiltrate in this disease.

[Causal assessment of drug-induced acute colitis. A prospective study of 58 consecutive cases]. / Responsabilité des médicaments dans la survenue des colites aiguës. Résultats d'une étude prospective de 58 cas consécutifs.

AIMS: The causal effect of drugs is underestimated in patients with inflammatory bowel disease. The aim of this study was to assess the causal implication of drugs in acute colitis. METHODS: A prospective study was conducted in 58 consecutive patients with an acute inflammation of the colonic mucosa. Recent drug intake was recorded and possible causal effects were analyzed exhaustively with respect to both intrinsic and bibliographic criteria. RESULTS: Causal assessment scores were high for 57 drugs and 41 patients. Drug-induced acute colitis was diagnosed in 35 cases. In 7 patients, physician practice had not taken into account drug use despite probable drug involvement. The main drugs implicated were antibiotics (n = 42) and non steroidal anti-inflammatory drugs (n = 10). CONCLUSION: Acute colitis is mainly induced by drugs.