Sternal reentry in a patient with previous deep sternal wound infection managed with horizontal titanium plate fixation

Redo open-heart surgery and sternal reentry in patients with previous deep sternal wound infection (DSWI) and absence of sternal integrity can be a delicate and morbid task due the lack of a dissection plane between the heart and the surrounding soft tissues. Delayed sternal reconstruction and osteosynthesis with horizontal titanium plating fixation (Synthes) following vacuum assisted therapy (KCI) has recently been proposed and adopted for the treatment of DSWI. We present such a case of a patient who was successfully reoperated for valve replacement three years after coronary artery bypass grafting complicated by DSWI and initially treated with titanium plate fixation

Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

Item does not contain fulltextRATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6 per thousand) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Cranial biomechanics in basal urodeles: the Siberian salamander (Salamandrella keyserlingii) and its evolutionary and developmental implications

Developmental changes in salamander skulls, before and after metamorphosis, afect the feeding capabilities of these animals. How changes in cranial morphology and tissue properties afect the function of the skull are key to decipher the early evolutionary history of the crown-group of salamanders. Here, 3D cranial biomechanics of the adult Salamandrella keyserlingii were analyzed under diferent tissue properties and ossifcation sequences of the cranial skeleton. This helped unravel that: (a) Mechanical properties of tissues (as bone, cartilage or connective tissue) imply a consensus between the stifness required to perform a function versus the fxation (and displacement) required with the surrounding skeletal elements. (b) Changes on the ossifcation pattern, producing fontanelles as a result of bone loss or failure to ossify, represent a trend toward simplifcation potentially helping to distribute stress through the skull, but may also imply a major destabilization of the skull. (c) Bone loss may be originated due to biomechanical optimization and potential reduction of developmental costs. (d) Hynobiids are excellent models for biomechanical reconstruction of extinct early urodeles

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

New highlights on stroma–epithelial interactions in breast cancer

Although the stroma in which carcinomas arise has been previously regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of tumor cells, it is now generally acknowledged that stromal changes are required for the establishment of cancer. In the present article, we discuss three recent publications that highlight the complex role the stroma has during the development of cancer and the potential for targeting the stroma by therapeutic approaches

Modes, mechanisms and evidence of bet hedging in rotifer diapause traits

In this contribution, we review our knowledge on bet-hedging strategies associated with rotifer diapause. First, we describe the ecological scenario under which bet hedging is likely to have evolved in three diapause-related traits in monogonont rotifer populations: (1) the timing of sex (because diapausing eggs are produced via sexual reproduction), (2) the sexual reproduction ratio (i.e. the fraction of sexually reproducing females) and (3) the timing of diapausing egg hatching. Then, we describe how to discriminate among bet-hedging modes and discuss which modes and mechanisms better fit the variability observed in these traits in rotifers. Finally, we evaluate the strength of the empirical evidence for bet hedging in the scarce studies available, and we call for the need of research at different levels of biological complexity to fully understand bet hedging in rotifer diapause

Effects of MDM2, MDM4 and TP53 Codon 72 Polymorphisms on Cancer Risk in a Cohort Study of Carriers of TP53 Germline Mutations

Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied.We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects.Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations