Dramatic decline in new HIV diagnoses in persons born in France in a large nationwide HIV cohort.

OBJECTIVES: As trends in new HIV diagnoses represent a measure of the HIV epidemic, we conducted a 6-year longitudinal study to evaluate the change in rates of new HIV diagnosis, stratified by birthplace, HIV risk groups and CD4 cell count at diagnosis in a large French multicentre cohort. STUDY DESIGN: We performed a retrospective cohort study using data from the mainland French Dat'AIDS cohort. METHODS: Data were obtained for subjects with a new HIV diagnosis date between 2013 and 2018. HIV diagnosis date was defined as the date of the first known positive HIV serology. RESULTS: Between 2013 and 2018, a total of 68,376 people living with HIV (PLHIV) were followed in the Dat'AIDS cohort; 9543 persons were newly diagnosed with HIV. The annual number of new HIV diagnoses decreased from 1856 in 2013, to 1149 in 2018 (-38.1%), P = 0.01; it was more pronounced among subjects born in France, from 858 to 484 (-43.6%), P < 0.01, than in those born abroad (-23.8%, from 821 to 626, P = 0.13). Among subjects born in France, the decrease over the period was -46.7% among men who have sex with men (MSM), -43.5% for heterosexual women and -33.3% for heterosexual men. CONCLUSION: Our findings show changes in HIV epidemiology in PLHIV born in France, with a decline around 40% in new HIV diagnoses, and a more pronounced decrease among MSM and heterosexual women. Our results support the long-term effectiveness of the antiretroviral therapy as a prevention strategy among the various tools for HIV prevention.

An extreme value theory approach for the early detection of time clusters. A simulation-based assessment and an illustration to the surveillance of Salmonella.

We propose a new method that could be part of a warning system for the early detection of time clusters applied to public health surveillance data. This method is based on the extreme value theory (EVT). To any new count of a particular infection reported to a surveillance system, we associate a return period that corresponds to the time that we expect to be able to see again such a level. If such a level is reached, an alarm is generated. Although standard EVT is only defined in the context of continuous observations, our approach allows to handle the case of discrete observations occurring in the public health surveillance framework. Moreover, it applies without any assumption on the underlying unknown distribution function. The performance of our method is assessed on an extensive simulation study and is illustrated on real data from Salmonella surveillance in France.

Stress-modulated remodeling of a non-homogeneous body.

Many soft tissues, and arteries in primis, exhibit residual stress after unloading, a characteristic related to the ability to self-organize their own constituents (cells and extracellular matrix proteins). This behavior can be theoretically predicted in a continuum mechanics framework assuming that the body self-remodels toward a homeostatic stress state. Open questions concern the characteristics of a stationary grown state, as dictated by the mechanical properties of the material and by the specific external load. In this paper, we illustrate a mathematical framework and we perform numerical simulations for the remodeling of a two-dimensional (axisymmetric) nonlinear elastic cylinder. In particular, we address the stress-modulated remodeling of the cylinder wall when local variations in the mechanical properties of the material occur. Our main result is that, as in one spatial dimension, the tendency of the system to homeostasis generates, thanks to the remodeling process, a residual stress that homogenizes the tension in the body under load. Possible physiological implications of this result are discussed in the final section.

A prospective observational study of medication errors in a pediatric emergency department.

We present a prospective, observational study evaluating the incidence of medication errors (ME) in a university hospital pediatric emergency department and describe their characteristics and determinants. A systematic analysis of the handwritten prescriptions was conducted by a clinician and pharmacist. Of 11,573 consecutively studied prescriptions in children under 15 years of age, the ME incidence was 0.9% (n=102). The incidence of errors found was statistically significantly higher in children older than 5 years (OR=2.05; P=0.026). There was no significant difference regarding the time of admission (P=0.544), the day of the week (P=0.940), or the affluence of people in attendance at the emergency department. The errors observed were all prescription errors. Most errors were related to analgesic (51%) and antibiotic (30%) treatments. No serious errors were reported. CONCLUSION: We found a low incidence of medication errors in this study. The validation of prescriptions by a senior multidisciplinary staff could contribute to limited medication errors. Measures should be continued to further reduce the incidence of drug errors by calling the attention of prescribers to the most common situations at risk of ME.

Extrasynaptic localization of glycine receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication.

Neurons of the rat supraoptic nucleus (SON) express glycine receptors (GlyRs), which are implicated in the osmoregulation of neuronal activity. The endogenous agonist of the receptors has been postulated to be taurine, shown to be released from astrocytes. We here provide additional pieces of evidence supporting the absence of functional glycinergic synapses in the SON. First, we show that blockade of GlyRs with strychnine has no effect on either the amplitude or frequency of miniature inhibitory postsynaptic currents recorded in SON neurons, whereas they were all suppressed by the GABA(A) antagonist gabazine. Then, double immunostaining of sections with presynaptic markers and either GlyR or GABA(A) receptor (GABA(A)R) antibodies indicates that, in contrast with GABA(A)Rs, most GlyR membrane clusters are not localized facing presynaptic terminals, indicative of their extrasynaptic localization. Moreover, we found a striking anatomical association between SON GlyR clusters and glial fibrillary acidic protein (GFAP)-positive astroglial processes, which contain high levels of taurine. This type of correlation is specific to GlyRs, since GABA(A)R clusters show no association with GFAP-positive structures. These results substantiate and strengthen the concept of extrasynaptic GlyRs mediating a paracrine communication between astrocytes and neurons in the SON.

[Evolution and radiologic surveillance on community-acquired pneumonia in children]. / Evolution et surveillance radiologiques des pneumopathies communautaires de l'enfant.

Although useful for the diagnosis of lower respiratory tract infections, chest X-rays have a weak specificity in the etiological diagnosis. It is of particular interest when complications are suspected. A radiological follow-up allows to exclude sequellae or a preexisting pulmonary abnormality; however follow-up X-rays are to be delayed 2 to 3 weeks after the clinical recovery due to the late radiological recovery. CT is indicated as a complementary investigation in cases of complications and sequellae.

[Ultrastructural study of a case of Miescher-Leder granulomatosis disciformis chronica et progressiva]. / Etude ultrastructurale d'un cas de granulomatose disciforme chronique et progressive de Miescher et Leder.

Ultrastructural study of a case of granulomatosis disciformis occurring on the legs of a 62-year-old woman. The diagnosis is based upon the contrast between the clinical aspect of necrobiosis lipoidica and the histologic aspect of inflammatory granulomatous infiltrate of dermis without necrobiosis nor palisading. Electron microscopic findings are: perivascular mixed cell infiltrate and histiocytic granuloma with lysosomial and phagocytic activity; degenerative and necrotic cellular alterations; modifications of collagen fibres with two types of fibres: the thinnest are the most numerous and have a mean diameter of 50 nm, the thickest of 110 nm; no significant lesions of capillary walls. These findings suggest the following succession of pathological events: cellular necrosis, lysosomial and phagocytic activity, scarring. Some descriptions of necrobiosis lipoidica and granuloma annulare seem to be quite similar and our findings are in favour of the unity of these three illnesses.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Age-impaired fluid homeostasis depends on the balance of IL-6/IGF-I in the rat supraoptic nuclei.

Adaptive metabolic changes associated with bacterial infections are likely to cause dehydration. Activation of hypothalamic neurons in the supraoptic nucleus that release anti-diuretic arginine-vasopressin in plasma provides water retention. Aging is characterized by arginine-vasopressin neuron hyper-activity and over-expression of pro-inflammatory cytokines like interleukin (IL)-6. Conversely, insulin-like growth factor (IGF)-I, known to exhibit anti-inflammatory properties, decreases with age. We compared activation of arginine-vasopressin neurons in adult (3 months) and aged (22 months) Wistar rats by measuring not only c-fos expression, plasma arginine-vasopressin and diuresis but also the expression of IL-6 and IGF-I in the supraoptic nuclei after intraperitoneal lipopolysaccharide injection. Aged rats displayed a heightened, shorter lasting activation of arginine-vasopressin neurons following lipopolysaccharide as compared to adults. IL-6 mRNA was 3-fold higher while IGF-I mRNA was 10-fold lower in aged than in adult rats. Brain pre-treatment with neutralizing anti-IL-6 antibodies or recombinant IGF-I in aged rats reversed lipopolysaccharide-induced anti-diuresis. These data extend the concept of neuroendocrine-immune interactions to the arginine-vasopressin neuronal system by establishing a relationship between brain IL-6/IGF-I balance and age-associated arginine-vasopressin neuronal dysfunction.

Absorption and fate of labelled canthaxanthin 15, 15'-3H2 in rainbow trout (Salmo gairdneri Rich.).

1. Using one force fed meal, absorption of labelled canthaxanthin 15,15'-3H2 was studied by collecting blood via caudal punction at regular intervals and measuring radioactivity in various tissues and organs of rainbow trout. 2. Canthaxanthin absorption showed a large variability between individuals irrespective of their sex. A rapid increase in the radioactivity linked to canthaxanthin 15,15'-3H2 is observed in the blood followed by a slow decrease. 3. Twenty-four and 72 hours after ingestion of labelled canthaxanthin by rainbow trout, the radioactivity was widely distributed. From the total radioactivity given, most was found 24 hours after the meal in the pyloric caeca, ovary and skin. Seventy-two hours after diet, the radioactivity increased in the muscle, liver and kidney. On the other hand, the percentage of radioactivity of intestine and caeca declined. 4. Data from absorption curve indicates that 0.86% of radioactivity ingested is present in the blood, suggesting that canthaxanthin is not readily transferred from the digestive tract. 5. The metabolic clearance of canthaxanthin (lambda = 0.0246/hr +/- 0.005) which would correspond to a half-life of 28 hours gives a preliminary idea of the digestive and metabolic utilization of canthaxanthin by the rainbow trout.

Comparative accumulations of labelled carotenoids (14C-astaxanthin, 3H-canthaxanthin and 3H-zeaxanthin) and their metabolic conversions in mature female rainbow trout (Oncorhynchus mykiss).

1. One force-fed meal containing labelled 14C-astaxanthin (14C-Ax) and 3H-canthaxanthin (3H-Cx) or 3H-zeaxanthin (3H-Zx) was given to eight mature female rainbow trout. Ninety-six hours after the test meal ingestion, trout were killed and liver, skin, muscle and ovaries were dissected out. 2. Ax accumulated slightly more in muscle than Cx but in all tissues Ax and Cx were very significantly more concentrated than Zx. 3. 3H-Zx metabolites were found only in the liver, whereas 14C-phoenicoxanthin was the only metabolic pigment from 14C-Ax detected and was found in all investigated tissues. 4. 3H-Ax was found in the liver of all trout indicating that 3H-Cx and 3H-Zx were Ax precursors, and that salmonids probably possess carotenoid oxidative pathways unknown until now. 5. Labelled retinol1 and retinol2 were detected only in the liver and 3H-Zx was largely the predominant precursor of these two vitamin A forms.

Unspecific arginine kinase of molecular weight 150 000. Amino acid composition, subunit structure and number of substrate binding sites.

The amino acid composition of unspecific arginine kinase of molecular weight 150 000 of Sabella pavonina muscle has been determined. If was found to be very similar to that of the phosphagen kinases previously studied. The subunit structure of the enzyme has been investigated by physical and chemical means. The data obtained from ultracentrifugation studies in 6 M guanidine hydrochloride and from molecular sieving and disc electrophoresis in 8 M urea, as well as the tryptic peptide mapping, suggest that Sabella muscle kinase is composed of four non-covalently linked polypeptide chains, with similar molecular weights. The number of binding sites for the nucleotide substrate ADP-Mg2+ has been estimated, using differential spectrophotometry and gel filtration on Sephadex columns. By both methods it was demonstrated that the enzyme contains two catalytic sites per protein molecule of molecular weight 150 000. Thus, arginine kinase from Sabella muscle, of molecular weight 150 000, consists of four similar polypeptide chains, but possesses only two substrate binding sites per tetrameric molecule.

Indigenous bacteria with antagonistic and plant-growth-promoting activities improve slow-filtration efficiency in soilless cultivation.

In tomato soilless culture, slow filtration allows one to control the development of diseases caused by pathogenic microorganisms. During the disinfecting process, microbial elimination is ensured by mechanical and biological factors. In this study, system efficacy was enhanced further to a biological activation of filter by inoculating the pozzolana grains contained in the filtering unit with 5 selected bacteria. Three strains identified as Pseudomonas putida and 2 as Bacillus cereus came from a filter whose high efficiency to eliminate pathogens has been proven over years. These 5 bacteria displayed either a plant growth promoting activity (P. putida strains) or antagonistic properties (B. cereus strains). Over the first months following their introduction in the filter, the bacterial colonisation of pozzolana grains was particularly high as compared to the one observed in the control filter. Conversely to Bacillus spp. populations, Pseudomonas spp. ones remained abundant throughout the whole cultural season. The biological activation of filter unit very significantly enhanced fungal elimination with respect to the one displayed by the control filter. Indeed, the 6-month period needed by the control filter to reach its best efficacy against Fusarium oxysporum was shortened for the bacteria-amended filter; in addition, a high efficacy filtration was got as soon as the first month. Fast colonization of pozzolana grains by selected bacteria and their subsequent interaction with F. oxysporum are likely responsible for filter efficiency. Our results suggest that Pseudomonas spp. act by competition for nutrients, and Bacillus spp. by antibiosis and (or) direct parasitism. Elimination of other fungal pathogens, i.e., Pythium spp., seems to differ from that of Fusarium since both filters demonstrated a high efficacy at the experiment start. Pythium spp. elimination appears to mainly rely on physical factors. It is worth noting that a certain percentage of the 5 pozzolana-inoculated bacteria failed to colonise the filter unit and were, thus, driven to the plants by the nutrient solution. Their contribution to the establishment of a beneficial microbial community in the rhizosphere is discussed.

Serum activity of mitochondrial aspartate aminotransferase: a sensitive marker of alcoholism with or without alcoholic hepatitis.

Serum activity of the mitochondrial isoenzyme of aspartate aminotransferase (mAST) was measured with an immunological method in 74 subjects. Fourty-six were chronic alcoholics with (30) or without (16) obvious alcoholic liver disease; 28 were nonalcoholic controls among whom 14 had acute or chronic viral hepatitis, the remaining 14 being healthy individuals. Mean mAST activity was much higher in all the alcoholic subjects, with or without liver disease, 10.4 and 1.95 units per liter, respectively, than in the healthy controls (0.43, p less than 0.001). The mean mAST to total AST ratio was similar in the healthy controls and in the patients with viral hepatitis (2.98 and 3.19%, NS), whereas it was about 4 times higher in the alcoholics with a sensitivity which reached 93% in the patients with alcoholic liver disease and 100% in those without. Both gamma-glutamyl transpeptidase and glutamate dehydrogenase serum activities were far less sensitive and specific. As almost all chronic alcoholics had similar abnormal values of mAST/total AST ratio, this leads to question whether "normal" liver may really exist in any of such subjects.