Multimodal Preventive Trial for Alzheimer's Disease: MIND-ADmini Pilot Trial Study Design and Progress.

BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

[Prevalence and Risk Factors of Chlamydia Trachomatis Infection Among Women Consulting at the Sexually Transmitted Infection Centre in la Reunion: A Cross-Sectional Study]. / Prévalence et Déterminants de L'infection à Chlamydia Trachomatis chez les Femmes Consultant en Centres de Dépistage à la Réunion: Une Étude Transversale.

Introduction: Chlamydia trachomatis (CT) infection is the commonest bacterial sexually transmitted infection (STI) in the world. Often asymptomatic, it can lead to significant complications in women. In France, since 2003, systematic screening for CT in STI center has been recommended for women aged less than 25 year. The main objective of this study was to determine CT prevalence in patients attending STI centers in Reunion Island. The second objective was to explore the determinants of this infection. Method: A cross-sectional survey using an anonymous questionnaire was conducted among women attending STI center in two hospitals in western and southern Reunion Island during one year. All women who had performed a CT PCR, based on vaginal self-swabs, were included. Results: Among the 620 patients tested, the prevalence of infection was 6.6% (95% CI [4.7-8.6]). By age group, the highest prevalence was between 12 and 17 years with 14.3% positive tests compared to 7.5% and 3.9% respectively in 18-24 and 25-67 year age group (p = 0.003). The risk factors for CT were a young age (p = 0.02), a first sexual intercourse between 11 and 14 years old (p = 0.01), lack of previous STI screening history (p = 0.02), and the following motives for seeking screening: "partner unfaithfulness" (p = 0.01) and "infected partner" (p = 0.02). Conclusion: This study highlights the high prevalence of CT among Reunionese minors. A more systematic screening and a reinforcement of STI awareness among young people in Reunion Island seem to be essential.

Diversity of cyanobacteria from thermal muds (Balaruc-Les-Bains, France) with the description of Pseudochroococcus coutei gen. nov., sp. nov.

Cyanobacteria are able to synthesize a high diversity of natural compounds that account for their success in the colonization of a variety of ecological niches. Many of them have beneficial properties. The mud from the thermal baths of Balaruc-Les-Bains, one of the oldest thermal baths in France, has long been recognized as a healing treatment for arthro-rheumatic diseases. To characterize the cyanobacteria living in these muds, several strains were isolated from the water column and biofilms of the retention basin and analyzed using a polyphasic approach. Morphological, ultrastructural and molecular (16S rRNA gene and 16S-23S ITS region sequencing) methods were employed to identify nine cyanobacterial strains belonging to the orders Chroococcales, Synechococcales, Oscillatoriales and Nostocales. The combination of morphological and genetic characteristics supported the description of a new genus and species with the type species as Pseudochroococcus coutei. The taxonomic diversity in the muds from Thermes de Balaruc-Les-Bains appears higher than previously documented, providing new candidate taxa for their observed therapeutic properties.

First assessment of sophrology for the treatment of subjective tinnitus.

OBJECTIVES: To assess (without comparison versus controls) the efficacy of a sophrology protocol adapted to disabling subjective tinnitus, in diminishing the handicap induced by perception of tinnitus. MATERIALS AND METHODS: One hundred and forty consecutive patients, aged 18-83 years, underwent a protocol comprising 6-8 sessions of sophrology over a 2-4 month period. Impact was assessed on pre- to post-treatment progression on the Tinnitus Handicap Inventory (THI), a validated questionnaire measuring handicap induced by tinnitus. RESULTS: Mean THI scores improved, by >20 points in 59.2% of cases (i.e., clinically significant decrease). Improvement was independent of tinnitus duration (>versus<6 months) and origin (acoustic trauma versus emotional shock), and concerned all 3 THI subscales (functional, catastrophic and emotional). CONCLUSION: The present sophrology protocol, dedicated to subjective tinnitus, reduced intrusiveness. Further studies with a control group are needed to confirm efficacy as compared to waiting list or other validated treatments such as cognitive behavioral therapies.

Poliposis adenomatosa familiar y prevención del cáncer colorrectal: reporte de un caso / Familial adenomatous polyposis and colorectal cancer prevention: A case report

Resumen La poliposis adenomatosa familiar (PAF) es una enfermedad hereditaria caracterizada por el crecimiento de múltiples adenomas epiteliales de distribución colorrectal, de patrón autosómico dominante causado por el defecto del gen APC. La degeneración de cáncer colorrectal en estos pacientes se considera inevitable en caso de no recibir el manejo terapéutico adecuado. Se presenta el caso de una paciente femenina de 25 años, quien acudió a consulta luego de presentar una modificación del patrón evacuatorio y dolor abdominal, sin antecedentes familiares asociados, por lo que se correlacionó con paraclínicos y se diagnosticó PAF, con la posterior implementación del manejo terapéutico. Se decidió hacer una revisión bibliográfica y actualización del tema resaltando los aspectos clínicos de reconocimiento de la enfermedad, así como las conductas a tomar en consideración para la prevención del cáncer en pacientes con PAF.

Abstract Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the growth of multiple colorectal epithelial adenomas. It is an autosomal dominant disorder caused by an APC gene defect. Degeneration to colorectal cancer is considered unavoidable in these patients if they do not receive adequate therapeutic management. We present the case of a 25-year-old female patient consulted after a change in her evacuation pattern and abdominal pain. She had no relevant family history associated but based on results of paraclinical tests diagnosis of FAP was made for which therapeutic management was implemented. This is a case report with a literature review and update of the topic highlighting clinical issues related to recognition of the disease and issues that should be taken into consideration for the prevention of cancer in patients with FAP.

Very Low Phytoplankton Diversity in a Tropical Saline-Alkaline Lake, with Co-dominance of Arthrospira fusiformis (Cyanobacteria) and Picocystis salinarum (Chlorophyta).

Lake Dziani Dzaha (Mayotte Island, Indian Ocean) is a tropical thalassohaline lake which geochemical and biological conditions make it a unique aquatic ecosystem considered as a modern analogue of Precambrian environments. In the present study, we focused on the diversity of phytoplanktonic communities, which produce very high and stable biomass (mean2014-2015 = 652 ± 179 µg chlorophyll a L-1). As predicted by classical community ecology paradigms, and as observed in similar environments, a single species is expected to dominate the phytoplanktonic communities. To test this hypothesis, we sampled water column in the deepest part of the lake (18 m) during rainy and dry seasons for two consecutive years. Phytoplanktonic communities were characterized using a combination of metagenomic, microscopy-based and flow cytometry approaches, and we used statistical modeling to identify the environmental factors determining the abundance of dominant organisms. As hypothesized, the overall diversity of the phytoplanktonic communities was very low (15 OTUs), but we observed a co-dominance of two, and not only one, OTUs, viz., Arthrospira fusiformis (Cyanobacteria) and Picocystis salinarum (Chlorophyta). We observed a decrease in the abundance of these co-dominant taxa along the depth profile and identified the adverse environmental factors driving this decline. The functional traits measured on isolated strains of these two taxa (i.e., size, pigment composition, and concentration) are then compared and discussed to explain their capacity to cope with the extreme environmental conditions encountered in the aphotic, anoxic, and sulfidic layers of the water column of Lake Dziani Dzaha.

Characterization of phototrophic microorganisms and description of new cyanobacteria isolated from the saline-alkaline crater-lake Dziani Dzaha (Mayotte, Indian Ocean).

The saline-alkaline crater-lake Dziani Dzaha (Mayotte, Indian Ocean) is dominated by the bloom-forming cyanobacterium Arthrospira. However, the rest of the phototrophic community remains underexplored because of their minute dimension or lower biomass. To characterize the phototrophic microorganisms living in this ecosystem considered as a modern analog of Precambrian environments, several strains were isolated from the water column and stromatolites and analyzed using the polyphasic approach. Based on morphological, ultrastructural and molecular (16S rRNA gene, 18S rRNA gene, 16S-23S internal transcribed spacer (ITS) region and cpcBA-IGS locus) methods, seven filamentous cyanobacteria and the prasinophyte Picocystis salinarum were identified. Two new genera and four new cyanobacteria species belonging to the orders Oscillatoriales (Desertifilum dzianense sp. nov.) and Synechococcales (Sodalinema komarekii gen. nov., sp. nov., Sodaleptolyngbya stromatolitii gen. nov., sp. nov. and Haloleptolyngbya elongata sp. nov.) were described. This approach also allowed to identify Arthrospira fusiformis with exclusively straight trichomes instead of the spirally coiled form commonly observed in the genus. This study evidenced the importance of using the polyphasic approach to solve the complex taxonomy of cyanobacteria and to study algal assemblages from unexplored ecosystems.

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix.

BACKGROUND: Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. OBJECTIVES: To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. METHODS: Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of the hands of 15 Caucasian women. Biopsies from lesional and adjacent nonlesional (NL) areas were processed for histological analysis or gene expression profiling. RESULTS: Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared with NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL vs. NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. CONCLUSIONS: Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. In particular, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.

Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation unit: case report.

BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.

Fibrin clot structure in patients with congenital dysfibrinogenaemia.

The clinical phenotype of patients with congenital dysfibrinogenaemia is highly heterogeneous, from absence of symptoms to mild bleeding, or thrombosis. A few mutations are associated with a specific phenotype, but generally the clinical course is not predictable. We investigated whether fibrin clot properties are correlated with the patient's phenotype and/or genotype. Ex vivo plasma fibrin clot characteristics, including turbidity, fibrinolysis, clot permeability and fibrin fibre density assessed by laser scanner confocal microscopy were investigated in 24 genotyped patients with congenital dysfibrinogenaemia compared to normal pool plasma. Compared to normal pool plasma, the patients were characterised by slower fibrin polymerisation (lag time, 345.10 ± 22.98 vs. 166.00s), thinner fibrin fibres (maximum absorbance, 0.15 ± 0.01 vs. 0.31), prolonged clot lysis time (23.72 ± 0.97 vs. 20.32 min) and larger clot pore size (21.5×10(-9) ± 4.48×10(-9) vs. 7.96×10(-9)cm(2)). Laser scanning confocal microscopy images confirmed disorganised fibrin networks in all patients. Patients with tendency to bleed showed an increased permeability compared to asymptomatic patients (p=0.01) and to patients with a thrombotic history (p=0.02) while patients with thrombotic history had a tendency to have a prolonged clot lysis time. Fibrin clot properties were similar among hotspot mutations. Further studies including a larger number of patients are needed to evaluate whether analysis of permeability and clot lysis time may help to distinguish the clinical phenotype in these patients and to assess differences according to the genotype.

Post-breakfast closed-loop glucose control is improved when accompanied with carbohydrate-matching bolus compared to weight-dependent bolus.

AIM: We compared post-breakfast closed-loop glucose control either matched with a carbohydrate-matching bolus or a weight-dependent bolus. METHODS: Twelve adults with type 1 diabetes consumed a 75 g CHO breakfast on two occasions. In random order, the breakfast was accompanied by a full carbohydrate-matching insulin bolus (8.30 U [7.50 U-11.50 U]) or a partial weight-dependent insulin bolus (0.047 U/kg; 3.45 U [2.95 U-3.75 U]). Postprandial glucose was regulated by sensor-responsive insulin and glucagon delivery. RESULTS: Glucose control after the weight-dependent bolus was safe and feasible (glucose values returned to pre-prandial levels after 5 h). However, 5-hr incremental area under the curve and percentage of time above 10 mmol/L were lower after the full bolus compared to the partial bolus (IAUC, 2.1 [0.8-4.2] mmol/L/hr vs 8.3 [6.5-11.4] mmol/L/hr; time in hyperglycaemia, 24% [6%-29%] vs 50% [25%-63%]; P < 0.001). CONCLUSIONS: Post-breakfast closed-loop glucose control without carbohydrate counting, but based on weight-dependent bolus is feasible but a carbohydrate-matching bolus provides better glucose control. CLINICAL TRIAL REGISTRY: NCT01519102.

The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis.

BACKGROUND: Factor XIII is a 320 kDa tetramer, comprising two enzymatic A-subunits and two carrier B-subunits (FXIII A2 B2). Activated FXIII (FXIIIa) catalyses the formation of ε-(γ-glutamyl)lysyl covalent bonds between γ-γ, γ-α and α-α chains of adjacent fibrin molecules and also cross-links the major plasmin inhibitor, α2-antiplasmin, to fibrin. OBJECTIVES: We investigated the role of FXIII cross-linking of fibrin directly in clot morphology and its functional effect on clot formation and lysis, in the absence of α2-antiplasmin. RESULTS AND CONCLUSIONS: Our data show that the presence of FXIII during clot formation results in fibrin clots that have a significant 2.1-fold reduction in pore size, as determined by the Darcy constant, Ks, and formed thinner fibers (74.7 ± 1.5 nm) and higher density of fibers compared with those without FXIII (86.0 ± 1.7 nm, P < 0.001), as determined by scanning electron microscopy. Additionally, fibrinolysis showed a significant increase in the time to lysis for clots formed in the presence of FXIII in both static and flow systems. These data demonstrate that independent of α2-antiplasmin, FXIII activity plays a role in increasing the stability of the fibrin clot by altering its structure and increasing the resistance to fibrinolysis.

Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation.

The risk of fractures after kidney transplantation is high. Hyperparathyroidism frequently persists after successful kidney transplantation and contributes to bone loss, but its impact on fracture has not been demonstrated. This longitudinal study was designed to evaluate hyperparathyroidism and its associations with mineral disorders and fractures in the 5 posttransplant years. We retrospectively analyzed 143 consecutive patients who underwent kidney transplantation between August 2004 and April 2006. The biochemical parameters were determined at transplantation and at 3, 12 and 60 months posttransplantation, and fractures were recorded. The median intact parathyroid hormone (PTH) level was 334 ng/L (interquartile 151-642) at the time of transplantation and 123 ng/L (interquartile 75-224) at 3 months. Thirty fractures occurred in 22 patients. The receiver operating characteristic (ROC) curve analysis for PTH at 3 months (area under the ROC curve = 0.711, p = 0.002) showed that a good threshold for predicting fractures was 130 ng/L (sensitivity = 81%, specificity = 57%). In a multivariable analysis, independent risk factors for fracture were PTH >130 ng/L at 3 months (adjusted hazard ratio [AHR] = 7.5, 95% CI 2.18-25.50), and pretransplant osteopenia (AHR = 2.7, 95% CI 1.07-7.26). In summary, this study demonstrates for the first time that persistent hyperparathyroidism is an independent risk factor for fractures after kidney transplantation.

Effect of preen oil on plumage bacteria: an experimental test with the mallard.

Feathers are essential for avian thermoregulation, communication or flight and a reduction of plumage condition may alter these functions and reduce individual fitness. Recently, descriptive studies provided evidence that birds carry feather-degrading bacteria on their plumage that have the ability to degrade feathers rapidly under laboratory conditions. If such bacteria reduce avian fitness, natural selection should favour the evolution of anti-bacterial defences to limit the effects of these detrimental microorganisms. Preening behaviour and associated preen gland secretions have been proposed as the main factor used by birds to limit feather-degrading bacterial growth and some recent in vitro studies provided evidence that uropygial oil inhibited the growth of some keratinolytic strains in passerines. However, preen oil antimicrobial properties remained to be experimentally tested in vivo. We conducted an experiment with mallards (Anas platyrhynchos) onto which we fixed a removable mechanism that blocked access to the uropygial gland in a first group of mallards, whilst birds in a second group had the same removable mechanism but access to their gland and a third group of birds had normal access to their gland. We found no significant effect of our treatment on total and feather-degrading bacterial loads. Three hypotheses may explain the discrepancy between our results and previous in vitro studies. First, in vitro studies may have over-estimated the bactericidal properties of the preen oil. Second, preen gland deprivation may have affected only a small portion of the feather-degrading bacterial community. Third, ducks and passerine oils might have different bactericidal properties.

Influences of bioavailability, trophic position, and growth on methylmercury in hakes (Merluccius merluccius) from Northwestern Mediterranean and Northeastern Atlantic.

Methylmercury (MeHg) determinations in hake, its food-chain, and the surrounding waters and sediments allowed us to show that the higher length or age normalized mercury concentrations of Northwestern Mediterranean (Gulf of Lions: GoL) muscle hakes compared to its Northeastern Atlantic (Bay of Biscay: BoB) counterpart are due to both biotic and abiotic differences between their ecosystems. Bioenergetic modeling reveals that the slower growth rate of Mediterranean hake favors the MeHg bioaccumulation in the fish muscle and explains most of the difference between GOL and BoB hake populations. In addition, the waters of the Mediterranean hake habitat favor a higher MeHg exposition, due to the upper position of the thermohalocline, where MeHg is formed. Furthermore, we show that, within the Mediterranean hake population, a major increase in the biomagnification power (the slope of the relationships between logMeHg and δ(15)N), from 0.36 up to 1.12, occurs when individuals enter adulthood, resulting from the combined effects of lowering growth rate and change in feeding habits. Finally, δ(15)N normalized Hg concentrations indicate that the highest Hg concentrations are for hake from the shelf edge and the lowest are for hake from the Rhône prodelta area, suggesting a lower Hg bioavailability in inshore environments, consistent with MeHg distributions in water, sediment, and preys.

Maternal investment of female mallards is influenced by male carotenoid-based coloration.

The differential allocation hypothesis predicts that females modify their investment in a breeding attempt according to its reproductive value. One prediction of this hypothesis is that females will increase reproductive investment when mated to high-quality males. In birds, it was shown that females can modulate pre-hatch reproductive investment by manipulating egg and clutch sizes and/or the concentrations of egg internal compounds according to paternal attractiveness. However, the differential allocation of immune factors has seldom been considered, particularly with an experimental approach. The carotenoid-based ornaments can function as reliable signals of quality, indicating better immunity or ability to resist parasites. Thus, numerous studies show that females use the expression of carotenoid-based colour when choosing mates; but the influence of this paternal coloration on maternal investment decisions has seldom been considered and has only been experimentally studied with artificial manipulation of male coloration. Here, we used dietary carotenoid provisioning to manipulate male mallard (Anas platyrhynchos) bill coloration, a sexually selected trait, and followed female investment. We show that an increase of male bill coloration positively influenced egg mass and albumen lysozyme concentration. By contrast, yolk carotenoid concentration was not affected by paternal ornamentation. Maternal decisions highlighted in this study may influence chick survival and compel males to maintain carotenoid-based coloration from the mate-choice period until egg-laying has been finished.

Difference of mercury bioaccumulation in red mullets from the north-western Mediterranean and Black seas.

The relationships between total mercury (Hg) concentration and stable nitrogen isotope ratio (delta(15)N) were evaluated in Mullus barbatus barbatus and M. surmuletus from the Mediterranean Sea and M. barbatus ponticus from the Black Sea. Mercury concentration in fish muscle was six times higher in the two Mediterranean species than in the Black Sea one for similar sized animals. A positive correlation between Hg concentration and delta(15)N occurred in all species. Increase in Hg concentration with delta(15)N was high and similar in the two Mediterranean fishes and much lower in the Black Sea species. Since this was neither related to trophic level difference between species nor to methylmercury (MeHg) concentration differences between the north-western Mediterranean and the Black Sea waters, we suggested that the higher primary production of the Black Sea induced a dilution of MeHg concentration at the base of the food webs.

[Domestic animals and accidents in children]. / Animaux domestiques et accidents chez l'enfant.

Young French children have 45,000,000 domestic pets, cats and dogs being widely prevalent (40%). Injuries due to domestic animals, especially bites, in particular from dogs, represent 1.9% of all children's injuries. On the quality of first aid in the field, i.e., whether the treatment is the first line in surgical specialized service or not, if it is a vital emergency, will depend the possibility of immediate complications, which include local superinfection (15%), functionals and further aesthetic sequelae. Some injuries due to large animals carry a polytraumatism, which should be treated like all polytraumatisms, whatever the aetiology. Learning to know and respect animals and their needs should remain the priority of families to avoid unexpected injury. Families also need to take charge of the responsible animal.