Return to sport and re-tears after anterior cruciate ligament reconstruction in children and adolescents

BACKGROUND: The primary objective of this study was to determine the time to and level of return to sports after anterior cruciate ligament (ACL) reconstruction in children and adolescents. The secondary objectives were to evaluate the risk of early ACL re-tear after return to sports and the risk of ACL tear in the contralateral knee. HYPOTHESIS: The time to return to sports in young patients is considerably longer than in adults. METHODS: A prospective multicentre study was conducted at 12 centres specialised in knee ligament surgery, in children and adolescents younger than 18 years, between 1 January 2015 and 31 October 2015. The patients were divided into a paediatric group with open physes and a skeletally mature group with closed physes. We recorded the time to return to sport, the type of sport resumed, and the occurrence of early re-tears on the same side. A poor outcome was defined as a re-tear or an objective IKDC score of C or D. A contralateral ACL tear was not considered a poor outcome. RESULTS: Of 278 included patients, 100 had open physes and 178 closed physes. In the open physes group, return to running occurred after 10.4±4.7 months, return to pivoting/contact sport training after 13.1±3.9 months, and return to pivoting/contact sport competitions after 13.8±3.8 months. Of the 100 patients, 80% returned to the same sport and 63.5% to pivoting/contact sport competitions. Re-tears occurred in 9% of patients, after 11.8±4.1 months, and contralateral tears in 6% of patients, after 17.2±4.4 months. In all, 19.4% of patients had a poor outcome, including 10.4% with an IKDC score of C or D and 9% with re-tears. In the group with closed physes, return to running occurred after 8.8±5.1 months, return to pivoting/contact sport training after 11.7±4.7 months, and return to pivoting/contact sport competitions after 12.3±4.2 months. Of the 178 patients, 76.9% returned to the same sport and 55.6% to pivoting/contact sport competitions. The re-tear rate was only 2.8% and the contralateral tear rate 5%. In all, 14.7% of patients had poor outcome, including 11.9% with an IKDC score of C or D and 2.8% with re-tears. No risk factors for re-tears were identified; the quadruple-bundle semitendinosus technique showed a non-significant association with re-tears. CONCLUSION: In young children, the return to sport time after ACL reconstruction is considerably longer than 1 year and the return to competitions occurs later and is more difficult. The results of this study indicate that reservations are in order when informing the family about return to sports prospects after ACL reconstruction. The return to pivoting/contact sport competitions should not be allowed until 14 months after surgery in young skeletally immature patients, and the risk of re-injury is high within the first 2 years. LEVEL OF EVIDENCE: IV, retrospective study

Genome-wide footprints in the carob tree (Ceratonia siliqua) unveil a new domestication pattern of a fruit tree in the Mediterranean

Intense research efforts over the last two decades have renewed our understanding of plant phylogeography and domestication in the Mediterranean basin. Here we aim to investigate the evolutionary history and the origin of domestication of the carob tree (Ceratonia siliqua), which has been cultivated for millennia for food and fodder. We used >1000 microsatellite genotypes to delimit seven carob evolutionary units (CEUs). We investigated genome-wide diversity and evolutionary patterns of the CEUs with 3557 single nucleotide polymorphisms generated by restriction-site associated DNA sequencing (RADseq). To address the complex wild vs. cultivated status of sampled trees, we classified 56 sampled populations across the Mediterranean basin as wild, seminatural or cultivated. Nuclear and cytoplasmic loci were identified from RADseq data and separated for analyses. Phylogenetic analyses of these genomic-wide data allowed us to resolve west-to-east expansions from a single long-term refugium probably located in the foothills of the High Atlas Mountains near the Atlantic coast. Our findings support multiple origins of domestication with a low impact on the genetic diversity at range-wide level. The carob was mostly domesticated from locally selected wild genotypes and scattered long-distance westward dispersals of domesticated varieties by humans, concomitant with major historical migrations by Romans, Greeks and Arabs. Ex situ efforts to preserve carob genetic resources should prioritize accessions from both western and eastern populations, with emphasis on the most differentiated CEUs situated in southwest Morocco, south Spain and eastern Mediterranean. Our study highlights the relevance of wild and seminatural habitats in the conservation of genetic resources for cultivated trees

Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.

OBJECTIVE: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD). DESIGN: We constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing. RESULTS: Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα(hep-/-) mice when compared with Pparα(-/-) mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα(-/-) mice became overweight during ageing while Pparα(hep-/-) remained lean. However, like Pparα(-/-) mice, Pparα(hep-/-) fed a standard diet developed hepatic steatosis in ageing. CONCLUSIONS: Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD

The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.

The gut microbiota-intestine-liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined. By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr <sup>+/+</sup> vs Pxr <sup>-/-</sup> C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota-PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr <sup>+/+</sup> but not Pxr <sup>-/-</sup> male mice. These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host's sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug-drug or food-drug interactions. Video abstract

Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension

Induction of general anesthesia frequently induces arterial hypotension, which is often treated with a vasopressor, such as phenylephrine. As a pure -agonist, phenylephrine is conventionally considered to solely induce arterial vasoconstriction and thus increase cardiac afterload but not cardiac preload. In specific circumstances, however, phenylephrine may also contribute to an increase in venous return and thus cardiac output (CO). The aim of this study is to describe the initial time course of the effects of phenylephrine on various hemodynamic variables and to evaluate the ability of advanced hemodynamic monitoring to quantify these changes through different hemodynamic variables. In 24 patients, after induction of anesthesia, during the period before surgical stimulus, phenylephrine 2 mu gkg(-1) was administered when the MAP dropped below 80% of the awake state baseline value for >3min. The mean arterial blood pressure (MAP), heart rate (HR), end-tidal CO2 (EtCO2), central venous pressure (CVP), stroke volume (SV), CO, pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance (SVR) were recorded continuously. The values at the moment before administration of phenylephrine and 5(T-5) and 10(T-10)min thereafter were compared. After phenylephrine, the mean(SD) MAP, SV, CO, CVP and EtCO2 increased by 34(13)mmHg, 11(9)mL, 1.02(0.74)Lmin(-1), 3(2.6)mmHg and 4.0(1.6)mmHg at T-5 respectively, while both dynamic preload variables decreased: PPV dropped from 20% at baseline to 9% at T-5 and to 13% at T-10 and SVV from 19 to 11 and 14%, respectively. Initially, the increase in MAP was perfectly aligned with the increase in SVR, until 150s after the initial increase in MAP, when both curves started to dissociate. The dissociation of the evolution of MAP and SVR, together with the changes in PPV, CVP, EtCO2 and CO indicate that in patients with anesthesia-induced hypotension, phenylephrine increases the CO by virtue of an increase in cardiac preload

Evidence for the Role of Horizontal Transfer in Generating pVT1, a Large Mosaic Conjugative Plasmid from the Clam Pathogen, Vibrio tapetis

The marine bacterium Vibrio tapetis is the causative agent of the brown ring disease, which affects the clam Ruditapes philippinarum and causes heavy economic losses in North of Europe and in Eastern Asia. Further characterization of V. tapetis isolates showed that all the investigated strains harbored at least one large plasmid. We determined the sequence of the 82,266 bp plasmid pVT1 from the CECT4600T reference strain and analyzed its genetic content. pVT1 is a mosaic plasmid closely related to several conjugative plasmids isolated from Vibrio vulnificus strains and was shown to be itself conjugative in Vibrios. In addition, it contains DNA regions that have similarity with several other plasmids from marine bacteria (Vibrio sp., Shewanella sp., Listonella anguillarum and Photobacterium profundum). pVT1 contains a number of mobile elements, including twelve Insertion Sequences or inactivated IS genes and an RS1 phage element related to the CTXphi phage of V. cholerae. The genetic organization of pVT1 underscores an important role of horizontal gene transfer through conjugative plasmid shuffling and transposition events in the acquisition of new genetic resources and in generating the pVT1 modular organization. In addition, pVT1 presents a copy number of 9, relatively high for a conjugative plasmid, and appears to belong to a new type of replicon, which may be specific to Vibrionaceae and Shewanelleacae

Adaptivni estimator brzine za bezsenzorsko vektorsko upravljanje asinkronim motorom zasnovan na umjetnoj neuronskoj mreži

This paper presents an adaptive speed observer for an induction motor using an artificial neural network with a direct field-oriented control drive. The speed and rotor flux are estimated with the only assumption that from stator voltages and currents are measurable. The estimation algorithm uses a state observer combined with an intelligent adaptive mechanism based on a recurrent neural network (RNN) to estimate rotor speed. The stator and rotor resistances are estimated by a simple Proportional-Integrator (PI) controller, which reduces sensitivity to variations, due essentially to the influence of temperature. The proposed sensorless control scheme is tested for various operating conditions of the induction motor drive. Experimental results demonstrate a good robustness against load torque disturbances, the estimated fluxes and rotor speed converge to their true values, which guarantees that a precise trajectory tracking with the prescribed dynamics.Ovaj članak opisuje adaptivni estimator brzine temeljen na umjetnoj neuronskoj mreži, koji se primijenjuje na asinkroni motor pogonjen izravnim vektorskim upravljanjem. Brzina i magnetski tok rotora estimiraju se uz pretpostavku dostupnosti mjerenja napona i struja statora. Algoritam koristi estimator stanja u kombinaciji s inteligentnim adaptivnim mehanizmom temeljenim na povratnoj neuronskoj mreži (RNN) kako bi se estimirala brzina rotora. Otpori statora i rotora estimiraju se jednostavnim Proporcionalno-Integralnim (PI) regulatorom, čime se smanjuje osjetljivost na varijacije uzrokovane utjecajem temperature. Predložena bezsenzorska upravljačka shema testirana je za različite radne uvjete asinkronog motora. Eksperimentalni rezultati pokazuju visoki stupanj robusnosti s obzirom na poremećaj momenta tereta, a estimirani tokovi i brzina rotora konvergiraju prema stvarnim vrijednostima što garantira precizno praćenje trajektorija uz zahtijevanu dinamiku