Clinical, Radiographic, and Patient-Reported Outcomes Associated with a Handheld Image-free Robotic-Assisted Surgical System in Total Knee Arthroplasty.

One of the primary aims of total knee arthroplasty (TKA) is restoration of the mechanical axis of the lower limb. Maintenance of the mechanical axis within 3° of neutral has been shown to result in improved clinical results and implant longevity. Handheld image-free robotic-assisted total knee arthroplasty (HI-TKA) is a novel way of performing TKA in the era of modern robotic-assisted TKA. The aim of this study is to assess the accuracy of achieving targeted alignment, component placement, clinical outcomes, as well as patient satisfaction after HI-TKA.

Fruit setting rewires central metabolism via gibberellin cascades.

Fruit set is the process whereby ovaries develop into fruits after pollination and fertilization. The process is induced by the phytohormone gibberellin (GA) in tomatoes, as determined by the constitutive GA response mutant procera However, the role of GA on the metabolic behavior in fruit-setting ovaries remains largely unknown. This study explored the biochemical mechanisms of fruit set using a network analysis of integrated transcriptome, proteome, metabolome, and enzyme activity data. Our results revealed that fruit set involves the activation of central carbon metabolism, with increased hexoses, hexose phosphates, and downstream metabolites, including intermediates and derivatives of glycolysis, the tricarboxylic acid cycle, and associated organic and amino acids. The network analysis also identified the transcriptional hub gene SlHB15A, that coordinated metabolic activation. Furthermore, a kinetic model of sucrose metabolism predicted that the sucrose cycle had high activity levels in unpollinated ovaries, whereas it was shut down when sugars rapidly accumulated in vacuoles in fruit-setting ovaries, in a time-dependent manner via tonoplastic sugar carriers. Moreover, fruit set at least partly required the activity of fructokinase, which may pull fructose out of the vacuole, and this could feed the downstream pathways. Collectively, our results indicate that GA cascades enhance sink capacities, by up-regulating central metabolic enzyme capacities at both transcriptional and posttranscriptional levels. This leads to increased sucrose uptake and carbon fluxes for the production of the constituents of biomass and energy that are essential for rapid ovary growth during the initiation of fruit set.

Towards a better understanding of the benefits and risks of country food consumption using the case of walruses in Nunavik (Northern Quebec, Canada).

Food insecurity affects Inuit communities. One solution is to consume locally harvested foods, named country foods. However, some country foods are not eaten as often as before, and pressures including contaminants and environmental changes threaten the health of Arctic fauna, thus its suitability for local consumption. By combining Inuit Knowledge with laboratory data, our study assessed the benefits and risks of walrus consumption by Inuit in Nunavik, Québec, Canada. It aimed to increase understanding of: 1) the hunt of healthy Atlantic walruses (Odobenus rosmarus rosmarus); 2) the safe preparation of walruses; 3) the nutritional benefits and risks of consuming walruses. To do so, we interviewed 34 hunters and Elders from Nunavik. Levels of mercury, omega-3 polyunsaturated fatty acids and selenium were evaluated from locally harvested walruses. Through the Nunavik Trichinellosis Prevention Program, a total of 755 Atlantic walrus samples, collected between 1994 and 2013, were tested for Trichinella nativa. Information on botulism was reviewed. While interviews informed on how to select healthy walruses and prepare them for consumption, laboratory analyses revealed that walruses had elevated levels of omega-3 fatty acids and selenium but low levels of mercury compared to some other wildlife. Only 3% of the 755 walruses were infected with T. nativa. Most walruses' infections were found within individuals from the South East Hudson Bay stock, where Inuit have thus decided to stop hunting since mid-2000s. Finally, although the number of outbreaks of trichinellosis related to the consumption of walruses has significantly reduced in Nunavik, botulism could continue to be an issue when igunaq (i.e. aged walrus) is not properly prepared. With the support of the Nunavik Trichinellosis Prevention Program and transmission of Inuit knowledge on igunaq preparation, the consumption of Atlantic walruses has the potential to help address issues related to food insecurity in Nunavik in the future.

Central Metabolism Is Tuned to the Availability of Oxygen in Developing Melon Fruit.

Respiration of bulky plant organs such as fleshy fruits depends on oxygen (O2) availability and often decreases with O2 concentration to avoid anoxia, but the relationship between O2 diffusional resistance and metabolic adjustments remains unclear. Melon fruit (Cucumis melo L.) was used to study relationships between O2 availability and metabolism in fleshy fruits. Enzyme activities, primary metabolites and O2 partial pressure were quantified from the periphery to the inner fruit mesocarp, at three stages of development. Hypoxia was gradually established during fruit development, but there was no strong oxygen gradient between the outer- and the inner mesocarp. These trends were confirmed by a mathematical modeling approach combining O2 diffusion equations and O2 demand estimates of the mesocarp tissue. A multivariate analysis of metabolites, enzyme activities, O2 demand and concentration reveals that metabolite gradients and enzyme capacities observed in melon fruits reflect continuous metabolic adjustments thus ensuring a timely maturation of the mesocarp. The present results suggest that the metabolic adjustments, especially the tuning of the capacity of cytochrome c oxidase (COX) to O2-availability that occurs during growth development, contribute to optimizing the O2-demand and avoiding the establishment of an O2 gradient within the flesh.

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.

BACKGROUND: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. METHOD: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. RESULTS AND CONCLUSION: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Pathological complete response in invasive breast cancer treated by skin sparing mastectomy and immediate reconstruction following neoadjuvant chemotherapy and radiation therapy: Comparison between immunohistochemical subtypes.

CONTEXT: Even if neoadjuvant chemotherapy (NACT) and oncoplastic techniques have increased the breast conserving surgery rate, mastectomy is still a standard for multifocal or extensive breast cancers (BC). In the prospect of increasing breast reconstruction, an alternative therapeutic protocol was developed combining NACT with neoadjuvant radiation therapy (NART), followed by mastectomy with immediate breast reconstruction (IBR). The oncological safety of this therapeutic plan still needs further exploration. We assessed pathological complete response (pCR) as a surrogate endpoint for disease free survival. METHODS: Between 2010 and 2016, 103 patients undergoing mastectomy after NACT and NART were recruited. After CT and RT were administrated, a completion mastectomy with IBR by latissimus dorsi flap was achieved 6 to 8 weeks later. pCR was defined by the absence of residual invasive disease in both nodes and breast. Histologic response was analyzed for each immunohistochemical subset. RESULTS: pCR was obtained for 53.4% of the patients. This pCR rate was higher in hormonal receptor negative (HER2 and triple negative) patients when compared to luminal tumours (69.7% vs 45.7%, p=0.023). DISCUSSION: The pCR rate found in this study is higher than those published in studies analyzing NACT (12.5%-27.1%). This can be explained by the combination of anthracycline and taxane, the use of trastuzumab when HER2 was overexpressed but also by RT associated to NACT. CONCLUSION: Inverting the sequence protocol for BC, requiring both CT and RT, allows more IBR without diminishing pCR and should therefore be considered as an acceptable therapeutic option.

Diagnostic value of angled oblique sagittal images of the supraspinatus tendon for the detection of rotator cuff tears on MR imaging.

PURPOSE: The goal of this study was to evaluate the added value of sagittal T2-weighted magnetic resonance imaging (MRI) of the supraspinatus tendon by comparison with a standard MRI protocol for the evaluation of the rotator cuff. MATERIALS AND METHODS: This retrospective single center study included 100 patients referred for MRI for suspected rotator cuff injuries. Two observers compared sagittal T2-weighted fat-suppressed orthogonal images of the distal portion of the supraspinatus muscle ("cuff" protocol) to those acquired according to the standard MRI protocol, which focuses on the glenoid. The two observers evaluated the appearance of each rotator cuff tendon and indicated whether the "cuff protocol" facilitated interpretation. RESULTS: The sensitivity and specificity for the detection of lesions ranged from 79 to 97% and 80 to 99% respectively. The interobserver variability coefficient was good for the supraspinatus (k=0.744). The new sequence helped localize and characterize rotator cuff injuries in 24-40% of the cases for the supraspinatus, in particular for partial tears and tendinopathies. CONCLUSION: The results of the specific MRI "cuff" protocol focusing on the supraspinatus are good, and helps facilitate interpretation of MRIs of the rotator cuff by non-specialist radiologists, in particular of the supraspinatus muscle.

A single enhanced phase is sufficient for the initial computed tomography evaluation of retroperitoneal tumors in children.

PURPOSE: The goal of this study was to evaluate the incremental value of unenhanced phase in the initial evaluation of retroperitoneal tumors in children by comparison with an enhanced phase alone using computed tomography (CT). MATERIALS AND METHODS: A total of 53 patients (26 girls, 27 boys) with a total of 53 tumors who had CT examination of the abdomen and pelvis for the initial assessment of retroperitoneal tumor were retrospectively included. All CT examinations were obtained with an unenhanced set of CT images and a set of CT images obtained after intravenous administration of iodinated contrast material. One junior and one senior radiologist independently evaluated the two sets in two separate reading sessions. CT images were analyzed for tumor calcifications, tumor location, vascular encasement, local invasion and tumor content. RESULTS: Calcifications were present in 24/53 tumors (45%). On the enhanced set, the senior radiologist was able to detect calcifications in 22/24 tumors (92%) and the junior radiologist in 20/24 tumors (83%), yielding sensitivities of 92% and 83%, and specificities of 96.5% and 100%, respectively. Inter-observer agreement was excellent (Kappa=0.89). Tumor location was correctly determined by the senior radiologist in 53/53 tumors (100%) and 37/53 tumors (70%) by the junior radiologist. Using the unenhanced set, the senior radiologist was able to assess vascular encasement in 26/53 tumors (49%) against 21/53 (39%) for the junior radiologist. For tumor content, agreement between the enhanced and combined unenhanced and enhanced CT was 77% for both radiologists. CONCLUSION: Enhanced CT performs as well as unenhanced CT for evidencing calcifications and is therefore sufficient for the initial assessment of retroperitoneal tumor in children.

Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography.

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of the sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.

Status of the SPIRAL2 injector commissioning.

The SPIRAL2 injector, installed in its tunnel, is currently under commissioning at GANIL, Caen, France. The injector is composed of two low energy beam transport lines: one is dedicated to the light ion beam production, the other to the heavy ions. The first light ion beam, created by a 2.45 GHz electron cyclotron resonance ion source, has been successfully produced in December 2014. The first beam of the PHOENIX V2 18 GHz heavy ion source was analyzed on 10 July 2015. A status of the SPIRAL2 injector commissioning is given. An upgrade of the heavy ion source, named PHOENIX V3 aimed to replace the V2, is presented. The new version features a doubled plasma chamber volume and the high charge state beam intensity is expected to increase by a factor of 1.5 to 2 up to the mass ∼50. A status of its assembly is proposed.

Comparison between Doppler ultrasonography and multiphase multidetector-row computed tomography in the detection of liver involvement in Rendu-Osler disease: An analysis of 62 patients.

PURPOSE: To evaluate the agreement between the Buscarini criteria on ultrasound (US) and multiphase contrast-enhanced multidetector-row computed tomography (MDCT) in the diagnosis and staging of liver involvement in hereditary hemorrhagic telangiectasia (HHT) (i.e., Rendu-Osler disease). To evaluate the role of variations in hepatic artery anatomy in the production of disagreement between these two imaging techniques. MATERIALS AND METHODS: This single center retrospective study included 62 patients with confirmed or suspected HHT. Each patient underwent Doppler US analyzed according to the Buscarini criteria and arterial and portal phase MDCT on the same day or one day apart. Liver involvement was classified as absent, slight, moderate or severe for each examination. Agreement was evaluated by the kappa and Bhapkar tests. Variations in hepatic arterial anatomy was analyzed by MDCT based on the Michel's classification and analysis of agreement and disagreement was performed using the Chi(2) test. RESULTS: Significant disagreement was identified between the two tests in 29 patients with κ=0.376 and a Bhapkar critical probability of P=0.0053. Staging of liver involvement was significantly more severe with MDCT in case of disagreement. A variant hepatic artery anatomy was identified in 12 patients with agreement and 7 patients with disagreement, but the difference was not significant (Chi(2)=0.297). CONCLUSION: The results of our study confirm the importance of associating contrast-enhanced MDCT with Doppler US in the evaluation of liver involvement in patients with HHT.

Development and Assessment of a Computer Algorithm for Stroke Vascular Localization Using Components of the National Institutes of Health Stroke Scale.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) was not intended to be used to determine the stroke's vascular distribution. The aim of this study was to develop, assess the reliability, and validate a computer algorithm based on the NIHSS for this purpose. METHODS: Two cohorts of patients with ischemic stroke having similar distributions of Oxfordshire localizations (total anterior, partial anterior, lacunar, and posterior circulation) based on neuroimaging were identified. The first cohort (n = 40) was used to develop a computer algorithm for vascular localization using a modified version of the NIHSS (NIHSS-Localization [NIHSS-Loc]) that included the laterality of selected deficits; the second (n = 20) was used to assess the reliability of algorithm-based localizations compared to those of 2 vascular neurologists. The validity of the algorithm-based localizations was assessed in comparison to neuroimaging. Agreement was assessed using the unweighted kappa (κ) statistic. RESULTS: Agreement between the 2 raters using the standard NIHSS was slight to moderate (κ = .36, 95% confidence interval [CI] .10-.61). Inter-rater agreement significantly improved to the substantial to almost perfect range using the NIHSS-Loc (κ = .88, 95% CI .73-1.00). Agreement was perfect when the 2 raters entered the data into the NIHSS-Loc computer algorithm (κ = 1.00, 95% CI 1.00-1.00). Agreement between the algorithm localization and neuroimaging results was fair to moderate (κ = .59, 95% CI .35-.84) and not significantly different from the localizations of either rater using the NIHSS-Loc. CONCLUSION: A computerized, modified version of the standard NIHSS can be used to reliably and validly assign the vascular distribution of an acute ischemic stroke.

Many respiratory viruses have temporal association with meningococcal disease

BACKGROUND: Previous ecological studies have shown a temporal and spatial association between influenza epidemics and meningococcal disease (MNG); however, none have examined more than two respiratory viruses. METHODS: Data were obtained in Chile between 2000 and 2005 on confirmed cases of MNG and all confirmed cases of respiratory viruses (influenza A and B; parainfluenza; adenovirus; and respiratory syncytial virus [RSV]). Both variables were divided by epidemiological weeks, age range, and regions. Models of transference functions were run for rates of MNG. RESULTS: In this period, 1022 reported cases of MNG and 34,737 cases of respiratory virus were identified (25,137 RSV; 4300 parainfluenza; 2527 influenza-A; 356 influenza-B; and 2417 adenovirus). RSV was the major independent virus temporally associated to MNG (it appears one week before MNG), followed by parainfluenza, influenza-B, adenovirus, and influenza-A. CONCLUSIONS: The rate of MNG in Chile is temporally associated to all of the respiratory viruses studied, but with variability according age range, and regions

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Consequences of low dose ionizing radiation exposure on the hippocampal microenvironment.

The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy), few studies have been conducted at much lower doses (≤ 2 Gy), where the response of the CNS (like many other tissues) may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT) animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.

The impact of increasing dose on overall survival in prostate cancer.

PURPOSE: To assess the impact of increasing dose on overall survival (OS) for prostate cancer patients. METHODS: Treatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028). Patients with prior malignancies were excluded. RESULTS: On multivariate analysis, dose, T stage, grade, marital status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios for OS declined monotonically with increasing dose, reaching 0.63 (95 % Confidence Interval 0.53-0.76) at ≥80 Gy. On subset analysis, neoadjuvant ADT significantly improved OS in high risk patients but was not significant in lower risk patients. The dose response was maintained across all risk groups. Medical comorbidities were balanced across all dose strata and sensitivity analysis demonstrated that other prognostic factors were unlikely to explain the observed dose response. CONCLUSIONS: This study suggests that increasing dose significantly improves OS in prostate cancer patients treated with radiotherapy.