Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification:

BACKGROUND: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest. METHODS: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration. RESULTS: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations. CONCLUSIONS: This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation

The development of descending projections from the brainstem to the spinal cord in the fetal sheep

<p>Abstract</p> <p>Background</p> <p>Although the fetal sheep is a favoured model for studying the ontogeny of physiological control systems, there are no descriptions of the timing of arrival of the projections of supraspinal origin that regulate somatic and visceral function. In the early development of birds and mammals, spontaneous motor activity is generated within spinal circuits, but as development proceeds, a distinct change occurs in spontaneous motor patterns that is dependent on the presence of intact, descending inputs to the spinal cord. In the fetal sheep, this change occurs at approximately 65 days gestation (G65), so we therefore hypothesised that spinally-projecting axons from the neurons responsible for transforming fetal behaviour must arrive at the spinal cord level shortly before G65. Accordingly we aimed to identify the brainstem neurons that send projections to the spinal cord in the mature sheep fetus at G140 (term = G147) with retrograde tracing, and thus to establish whether any projections from the brainstem were absent from the spinal cord at G55, an age prior to the marked change in fetal motor activity has occurred.</p> <p>Results</p> <p>At G140, CTB labelled cells were found within and around nuclei in the reticular formation of the medulla and pons, within the vestibular nucleus, raphe complex, red nucleus, and the nucleus of the solitary tract. This pattern of labelling is similar to that previously reported in other species. The distribution of CTB labelled neurons in the G55 fetus was similar to that of the G140 fetus.</p> <p>Conclusion</p> <p>The brainstem nuclei that contain neurons which project axons to the spinal cord in the fetal sheep are the same as in other mammalian species. All projections present in the mature fetus at G140 have already arrived at the spinal cord by approximately one third of the way through gestation. The demonstration that the neurons responsible for transforming fetal behaviour in early ontogeny have already reached the spinal cord by G55, an age well before the change in motor behaviour occurs, suggests that the projections do not become fully functional until well after their arrival at the spinal cord.</p

Planck early results I : The Planck mission

Peer reviewe

Planck pre-launch status : The Planck mission

Peer reviewe

Le syndrome ASIA associé aux implants mammaires : lien de causalité ou association fortuite ?

International audienceObjective: The "Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants" (ASIA syndrome) described in 2011 by Shoenfeld and Agmon-Levin is believed to be the consequence of several immunological dysfunctions triggered by exposure to an adjuvant. Controversies regarding the existence of this syndrome and its possible link to silicone breast implants (SBI) have been growing via social networks and patient groups. The objective of our review was to identify all published cases of ASIA syndromes in SBI carriers to determine the circumstances of onset, key characteristics, and possible biases.Method: A literature search of the Pubmed database selecting only original articles written in English between 2011 and 2019 found 126 cases of ASIA syndromes, defined according to the criteria of Shoenfeld and Agmon-Levin, associated with SBI.Results: This syndrome was diagnosed in nearly ¾ cases in a context of prosthetic complications (rupture, effusion, peri-prosthetic shell, infection) with a median time interval of 4 years between SBI implantation and the onset of symptoms. Explantation of the SBI led to an improvement in symptoms in about half of the cases. However, animal, biological and histological studies have provided conflicting results on the links between silicone and dysimmune syndromes.Conclusion: Women should be clearly, fairly and appropriately informed of our uncertainties about ASIA syndrome. Mandatory reporting of dysimmune syndromes occurring in silicone MI carriers would increase our knowledge of this still poorly understood condition, for which a genetic predisposition is being investigated

Staphylococcus aureus broncho-pulmonary infections

International audienceStaphylococcus aureus accounts for 2-5% of the etiologies of community-acquired pneumonia. These infections occur mainly in elderly patients with comorbidity, after a respiratory viral infection. S.~aureus could also be responsible for necrotizing pneumonia, which occurs in young subjects, also after flu. Necrotizing pneumonia are associated with the production of a particular staphylococcal toxin called Panton-Valentine leukocidin, responsible for pulmonary focal necrosis, occurrence haemoptysis, leucopenia, and death. In Europe, these strains are still predominantly sensitive to anti-staphylococcal penicillin, which must be used at high dosage intravenously in combination with an antibiotic that reduces toxin production such as clindamycin, and intravenous immunoglobulin in severe cases. The mortality rate is estimated at 50%. In addition, S.~aureus is one of the pathogens involved in early respiratory infections in cystic fibrosis patients, in whom methicillin resistance plays an important prognostic role. However, the involvement of S.~aureus in COPD exacerbations is rare. Finally, S.~aureus represents 20~to 30% of cases of hospital-acquired pneumonia, including ventilator-associated pneumonia. In these cases, methicillin-resistance is common and requires the use of glycopeptides or linezolid. The place of new anti-staphylococcal antibiotics such as new generation cephalosporins or tigecyclin remains to be defined

Hydration and clinical warning signs of dengue fever in primary care: An observational prospective study

International audienceOBJECTIVES: Dengue fever is an arbovirosis expanding worldwide, for which hydration has been reported to reduce the risk of hospitalization. Our objective was to estimate the volume of hydration in Reunionese patients with dengue. METHODS: A prospective observational study included patients presenting with a ’dengue-like’ syndrome in ambulatory care. General practitioners recruited patients during consultation, and beverage consumption over the previous 24 hours was reported at two different times. Warning signs were defined according to the 2009 WHO guidelines. RESULTS: GPs included 174 patients from April to July 2019. Average oral hydration volume was 1863 mL and 1944 mL, at the 1st and 2nd medical consultations, respectively. Water was the most wide consumed liquid. Drinking at least 5 glasses of liquid was significantly associated with fewer clinical warning signs at the 1st medical consultation (p = 0.044). CONCLUSIONS: Sufficient hydration volume could prevent dengue warning signs. Further studies with standardized measurement of hydration would be needed