MACVIA-LR,Reference site of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) in Languedoc Roussillon

The Région Languedoc-Roussillon is the umbrella organisation for an interconnected and integrated project on AHA covering the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing. All sub-activities (A1: electronic pharmaceutical file, A2: falls prevention initiative, A3: frailty, B3: chronic respiratory diseases, chronic diseases with comorbidities, oral health and hepatitis virus C chronic infection, C2 and D4 active and independent living and handicap) are included in MACVIA-LR that has a strong political commitment and includes all stakeholders (public, private, patients, policy makers). It is one of the Reference Sites of the European Innovation Partnership on Active and Healthy Ageing built around chronic diseases, ageing and handicap. The framework of MACVIA-LR has the vision that the prevention and management of CDs is essential for AHA promotion and for the reduction of handicap. The main objective of MACVIA-LR is to develop innovative solutions for a network of Living Labs in order to improve the care of patients affected by CDs in the Languedoc-Roussillon area and to disseminate the innovation.     

HIV-1 Protein gp120 Induces Mouse Lung Fibroblast-to-Myofibroblast Transdifferentiation via CXCR4 Activation

BackgroundIndividuals with HIV have ～2-fold increased risk of developing pulmonary fibrosis. The mechanism(s) by which this occurs has yet to be determined. HIV-1 protein gp120 activates CXCR4 in the lymphocyte, promoting a variety of intracellular signaling pathways including those common to TGFβ1 associated with lung fibroblast-to-myofibroblast transdifferentiation. We hypothesized that gp120 promotes pulmonary fibrotic changes via activation of CXCR4 in the lung fibroblast.MethodsMouse primary lung fibroblasts (PLFs) were cultured ± gp120, then analyzed for α-SMA expression and stress fiber formation. In parallel, PLFs were cultured ± gp120 ± AMD3100 (a CXCR4 antagonist), and α-SMA, pan and phospho-Akt, and total and phospho-MAPK (or ERK1/2) protein expression was quantified. Finally, lungs and PLFs from wild-type and HIV-1 transgenic mice were analyzed for hydroxyproline and α-SMA content.Resultsgp120 treatment increased α-SMA expression and myofibroblast differentiation in PLFs. gp120 treatment activated phosphorylation of ERK1/2, but not PI3K-Akt. Pretreatment with AMD3100 inhibited gp120-induced ERK1/2 phosphorylation and gp120-induced α-SMA expression. In parallel, there was a significant increase in hydroxyproline content in lungs from older HIV-1 transgenic mice and a >3-fold increase in α-SMA expression in PLFs isolated from HIV-1 transgenic mice.Conclusionsgp120 induces α-SMA expression and fibroblast-to-myofibroblast transdifferentiation by activating the CXCR4-ERK1/2 signaling pathway in mouse PLFs. Lungs of older HIV-1 transgenic mice contain higher hydroxyproline content and their PLFs have a striking increase in α-SMA expression. These results suggest a mechanism by which individuals with HIV are at increased risk of developing pulmonary fibrotic changes as they age.     

Placental pathology and neurological morbidity in preterm infants during the first two weeks after birth

Background

The placenta plays a crucial role during pregnancy and dysfunction causes long-term neurological problems. Identifying placenta-related risks for neurological problems shortly after birth may provide clues for early interventions aiming to improve neurological outcome.

Objective

To determine the association between placental pathology and neurological morbidity in preterm infants during the first two weeks after birth.

Study design

Placentas of 52 singleton, preterm infants (GA: 25–31 weeks, BW: 560–2250 grammes) were examined for histopathology. The infants' neurological condition shortly after birth was determined by assessing the quality of their general movements (GMs): normal, abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS) was also assigned.

Results

Examination of the placentas revealed maternal vascular underperfusion (n = 29), ascending intrauterine infection (AIUI) (n = 19), villitis of unknown aetiology (n = 6), chronic deciduitis (n = 11), foetal thrombotic vasculopathy (FTV) (n = 9), and elevated nucleated red blood cells (NRBCs) as a marker for foetal hypoxia (n = 7). None of the placental lesions were significantly associated with the quality of GMs or MOS.

Conclusions

This study indicated that placental lesions were not associated with infants' neurological condition as measured by the quality of their general movements during the first two weeks after birth.     

Auditory neural myelination is associated with early childhood language development in premature infants

Background

Auditory neural myelination (ANM) as evaluated by auditory brainstem evoked response (ABR) during the neonatal period has been used as a surrogate outcome for long-term neurodevelopment. The validity of ANM as a surrogate outcome for long-term neurodevelopment has not been well studied.

Aim

Evaluate the association of ABR I–V interpeak latency (IPL), an index of ANM, at 35 week postmenstrual age (PMA) with language outcome at 3 years of age.

Design

Prospective study.

Subjects

24–33 week gestational age (GA) infants were eligible if they did not meet exclusion criteria: craniofacial malformation, chromosomal disorders, deafness, auditory dys-synchrony, TORCH infection, or non-English speaking parents. Infants with malignancy, head injury, encephalopathy, meningitis, blindness, or who died or relocated were also excluded.

Outcome measures

ABRs were performed at 35 week PMA using 80 dB nHL and I–V IPL (ms) measured. Auditory Comprehension (AC) and Expressive Communication (EC) were evaluated by a speech-language pathologist at 3 years of age using Preschool Language Scale.

Results

Eighty infants were studied. The mean GA and birth weight of infants were 29.2 weeks and 1336 g, respectively. There was association of worse ear I–V IPL and better ear I–V IPL with AC (Coefficient − 5.4, 95% CI: − 9.8 to − 0.9 and Coefficient − 5.5, 95% CI: − 10  to−0.9, respectively) and EC (Coefficient − 5.6, 95% CI: − 9.5  to−1.8 and Coefficient − 6.7, 95% CI: − 10.6  to−2.7, respectively) after controlling for confounders.

Conclusion

The neonatal I–V IPL is a predictor of language development at 3 years of age in preterms.     

Optimization of a rapid test for antibodies to the Chlamydia trachomatis antigen Pgp3

Serological surveillance for trachoma could allow monitoring of transmission levels in areas that have achieved elimination targets. Platforms that allow testing in basic laboratories or testing of easy-to-manage samples such as dried blood spots would contribute to the feasibility of serologic testing. Blood from 506 1–12-year-olds in 2 villages in Kongwa district, Tanzania, was tested for antibodies against the antigen Pgp3. Whole blood, plasma, and dried blood spots (DBS) were tested in lab and field settings using a cassette-enclosed Pgp3 lateral flow assay (LFA-cassette) and a pared-back “dipstick” assay (LFA-dipstick). DBS were also tested with a bead-based multiplex assay (MBA). There was no significant difference in antibody positivity between the MBA and either LFA format (ranging from 42.5% to 48.4%). Interrater agreement between an expert rater and 3 different raters in field and lab settings was uniformly good, with Cohen's kappa >0.81 in all cases.     

Critical congenital heart disease screening does not predict car seat tolerance screen outcomes

BackgroundCar Seat Tolerance Screening (CSTS) and Critical Congenital Heart Disease (CCHD) screens were both implemented to identify infants with cardiorespiratory distress. We hypothesized that the CCHD screen would be poorly sensitive to predict a failed CSTS for many reasons.MethodsRetrospective record review of infants in 2013 who qualified for CSTS. Calculated sensitivity, specificity, predictive value (PV) of a failed CCHD screen to identify those infants who failed their CSTS.Results270 subjects underwent both screens and 14 failed a CSTS (5.2%). Of these, 1 failed the CCHD and 1 had an equivocal result. None were diagnosed with CCHD. An abnormal CCHD (failed or equivocal) had a sensitivity = 14.3% and a PV = 40% for predicting CSTS failure.ConclusionsCCHD screening is poorly sensitive and has poor PV for identifying those infants who are at risk of failing a CSTS. We therefore cannot recommend replacement of the CSTS with routine CCHD screening.