Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice.

Low dose ionizing radiation (LDIR) is known to have a protective effect on atherosclerosis in rodent studies, but how it impacts different cells types involved in lesion formation remains incompletely understood. We investigated the immunomodulatory response of different doses and dose-rates of irradiation in ApoE-/- mice. Mice were exposed to external γ rays at very low (1.4 mGy.h-1) or low (50 mGy.h-1) dose-rates, with cumulative doses spanning 50 to 1000 mGy. Flow cytometry of circulating cells revealed a significant decrease in pro-inflammatory Ly6CHi monocytes at all cumulative doses at low dose-rate, but more disparate effects at very low dose-rate with reductions in Ly6CHi cells at doses of 50, 100 and 750 mGy only. In contrast, Ly6CLo monocytes were not affected by LDIR. Similarly, proportions of CD4+ T cell subsets in the spleen did not differ between irradiated mice and non-irradiated controls, whether assessing CD25+FoxP3+ regulatory or CD69+ activated lymphocytes. In the aorta, gene expression of cytokines such as IL-1 and TGF-ß and adhesion molecules such as E-Selectin, ICAM-1, and VCAM-1 were reduced at the intermediate dose of 200 mGy. These results suggest that LDIR may reduce atherosclerotic plaque formation by selectively reducing blood pro-inflammatory monocytes and by impairing adhesion molecule expression and inflammatory processes in the vessel wall. In contrast, splenic T lymphocytes were not affected by LDIR. Furthermore, some responses to irradiation were nonlinear; reductions in aortic gene expression were significant at intermediate doses, but not at either highest or lowest doses. This work furthers our understanding of the impact of LDIR with different dose-rates on immune system response in the context of atherosclerosis.

Specific antibacterial activity of copper alloy touch surfaces in five long-term care facilities for older adults.

BACKGROUND: Pathogens involved in healthcare-associated infections can quickly spread in the environment, particularly to frequently touched surfaces, which can be reservoirs for pathogens. AIM: The purpose of this study was to investigate naturally occurring bacterial contamination on touch surfaces in five French long-term care facilities and to compare bacterial populations recovered from copper and control surfaces. METHODS: More than 1300 surfaces were sampled. The collected bacteria were identified to obtain a global view of the cultivable bacterial populations colonizing touch surfaces. Haemolytic colonies and putative pathogens were also screened using specific agar plates and then identified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. In total, more than 3400 colonies were analysed. FINDINGS: Staphylococcus and Micrococcus were the two predominant genera present on touch surfaces, respectively occurring on 51.8% and 48.0% of control surfaces. In these facilities with relatively low bioburden, copper surfaces efficiently reduced the occurrence frequencies of three genera: Staphylococcus, Streptococcus and Roseomonas. Pathogenic species such as Staphylococcus aureus, Enterococcus faecalis and E. faecium were observed in very few samples. In addition, meticillin-resistant S. aureus was observed on five control surfaces and one copper surface. CONCLUSION: Contamination of healthcare facilities touch surfaces can be the source for the spread of bacteria through the institution. This in situ study shows that the frequency of the contamination as well as the specific bacterial population bioburden is reduced on copper alloy surfaces.

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

[The persistence of ontogenic characteristics in the adult masseter muscle]. / Persistance de caractères ontogéniques dans le muscle masséter adulte.

During embryonic and foetal development, the masseter is formed from two successive generations of muscle fibers in a manner which is very similar to that which has been previously described for other skeletal muscles. This phenotype is characterised by the persistence of ontogenic myosin isoforms (embryonic and foetal myosin heavy chains, embryonic light chain) and by the presence of two distinct populations of fibers: small diameter fibers which coexpress the embryonic, foetal and fast isoforms of the myosin heavy chains but never express the slow isoform; large diameter fibers which express the slow myosin heavy chain either exclusively or in variable associations with the other isoforms. These characteristics of the human masseter muscle probably correspond not only to its embryological origin and its special innervation, but also to the functional constraints to which it is submitted after birth.

Characterization of a novel type II restriction-modification system, Sth368I, encoded by the integrative element ICESt1 of Streptococcus thermophilus CNRZ368.

A novel type II restriction and modification (R-M) system, Sth368I, which confers resistance to phiST84, was found in Streptococcus thermophilus CNRZ368 but not in the very closely related strain A054. Partial sequencing of the integrative conjugative element ICESt1, carried by S. thermophilus CNRZ368 but not by A054, revealed a divergent cluster of two genes, sth368IR and sth368IM. The protein sequence encoded by sth368IR is related to the type II endonucleases R.LlaKR2I and R.Sau3AI, which recognize and cleave the sequence 5'-GATC-3'. The protein sequence encoded by sth368IM is very similar to numerous type II 5-methylcytosine methyltransferases, including M.LlaKR2I and M.Sau3AI. Cell extracts of CNRZ368 but not A054 were found to cleave at the GATC site. Furthermore, the C residue of the sequence 5'-GATC-3' was found to be methylated in CNRZ368 but not in A054. Cloning and integration of a copy of sth368IR and sth368IM in the A054 chromosome confers on this strain phenotypes similar to those of CNRZ368, i.e., phage resistance, endonuclease activity of cell extracts, and methylation of the sequence 5'-GATC-3'. Disruption of sth368IR removes resistance and restriction activity. We conclude that ICESt1 encodes an R-M system, Sth368I, which recognizes the sequence 5'-GATC-3' and is related to the Sau3AI and LlaKR2I restriction systems.

[The first appearance of Meckel's cartilage in the fetus]. / Le cartilage de Meckel au début de la période foetale.

Meckel's cartilage plays an important role in the topographical organisation and in the differentiation of the facial structure during the embryonal and even much later during the foetal period. Our observations on serial sections carried out in two human foetuses aged 12 and 16 weeks indicate that the two dorsal (tympanic) and ventral (mandibular) branches of Meckel's cartilage are perfectly defined at 16 weeks. In the dorsal branch, the primordia of the incus and of head of the malleus are still composed on non-ossified cartilage. In the ventral branch, it is also possible to describe at 16 weeks three posterior, medial and anterior parts which are composed of cartilage. The initiating role played by the ventral part of Meckel's cartilage on the ossification of the mandible leads during the embryonal period to the formation of the mandibular primary growth center, which is therefore clearly defined in our first stage at 12 weeks. The partial fibrous evolution and the regression of the major part of the ventral branch of Meckel's cartilage only start after 16 weeks of intrauterine life.

Renal biopsy and family studies in 65 children with isolated hematuria.

We have investigated 65 children with isolated hematuria persisting for at least a year. Renal biopsy specimens were studied by light microscopy, electron microscopy and immunofluorescence with antisera specific against basement membrane components. The majority of the biopsies (62/65) showed variable histologic abnormalities. Four categories could be distinguished on combined histological and clinical criteria: Alport syndrome (n = 8), benign hematuria (n = 33, familial in 23), IgA nephropathy (n = 16) and increase in mesangial cells and matrix (n = 5). On the basis of our results, we suggest that a renal biopsy can establish diagnosis and prognosis in those children with isolated hematuria where the family history is negative. If the family has adult male individuals with isolated hematuria, a biopsy can usually be avoided, since this family history effectively excludes Alport syndrome. The use of antisera against basement membrane components did not allow a differentiation between Alport syndrome and benign hematuria. Goodpasture serum immunofluorescence was variable in the former and normally present in the latter.