Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life

Models of in vitro spermatogenesis

Understanding the mechanisms that lead to the differentiation of male germ cells from their spermatogonial stem cells through meiosis to give rise to mature haploid spermatozoa has been a major quest for many decades. Unlike most other cell types this differentiation process is more or less completely dependent upon the cells being located within the strongly structured niche provided by mature Sertoli cells within an intact seminiferous epithelium. While much new information is currently being obtained through the application and description of relevant gene mutations, there is still a considerable need for in vitro models with which to explore the mechanisms involved. Not only are systems of in vitro spermatogenesis important for understanding the basic science, they have marked pragmatic value in offering ex vivo systems for the artificial maturation of immature germ cells from male infertility patients, as well as providing opportunities for the transgenic manipulation of male germ cells. In this review, we have summarized literature relating to simplistic culturing of germ cells, co-cultures of germ cells with other cell types, especially with Sertoli cells, cultures of seminiferous tubule fragments, and briefly mention the opportunities of xenografting larger testicular pieces. The majority of methods are successful in allowing the differentiation of small steps in the progress of spermatogonia to spermatozoa; few tolerate the chromosomal reduction division through meiosis, and even fewer seem able to complete the complex morphogenesis which results in freely swimming spermatozoa. However, recent progress with complex culture environments, such as 3-d matrices, suggest that possibly success is now not too far away

An Objective Method to Assess and Recommend Exertion and Exercise Targets for Return to Play Post concussion

Introduction. Concussions are of significant concern for athletic trainers, and there is a critical need to objectively and safely allow an athlete to return to play. In sports the objective is return as safely and soon as possible. Exertion is a consideration regarding progressing an athlete back to play. The ability to exert in cardiovascular and strength and conditioning contexts are two critical steps in most return to play protocols. Being able to make objective recommendations is urgently needed, as trial and error leads to unnecessary risk of eliciting symptoms and/or causing setbacks. Objective. The object of this paper is to present the athletic trainer with data associated with a methodology that can be used to aid in designing a cardiovascular and strength training program post concussion. This objective measure does not rely on subjective patient reports of symptoms and utilizes a reflex based assessment method. Description. The transient exertion related carotid (TERC) murmur is a murmur that is heard at the carotid arteries during exercise. It normally is heard at around a heart rate of 150, but is heard at lower heart rates in patients who have sustained a concussion. Listening for the TERC murmur during a cardiovascular and strength training assessment can be used to provide information to the athletic trainer about safer target heart rates or safer lifting strategies post-concussion. We present data concerning 71 athletes (mean age 20.8 years) who were assessed for cardiovascular conditioning and body weight assessment. With 73% of the cardio assessment subjects, a TERC murmur was detected at a heart rate of 127.2 bpm (± 16 SD). For the strength assessment 42.1% had a TERC murmur. Clinical advantages. The clinical advantage of the TERC murmur is that it can be utilized by any athletic trainer trained to take a blood pressure. It provides objective information concerning safe target heart rates that will allow an athletic trainer to recommend appropriate exercise prescriptions. The TERC murmur assessment can also be used to help guide strength training protocols to facilitate safe return. Being able to safely recommend a means by which an athlete can recommence their training (cardiovascular and/or strength training) may accelerate return to play as well as aid in keeping the athlete happy, healthy and engaged

Pilot Study For Using Fitbit Activity Trackers To Monitor And Predict Onset Of CAR-T Cell Immunotherapy Related Adverse Events Including Cytokine Release Syndrome

Introduction: Immunotherapy using T Cells with engineered chimeric antigen receptors (CAR) is a revolutionary modality for treating cancer, especially B cell malignancies. It also has specific toxicities. The most common toxicities observed are cytokine-release syndrome (CRS) and neurotoxicity. These therapy-related adverse events can range from mild to fatal. If appropriately and timely treated, they have a good prognosis. Thus, further insight into predictive biomarkers can help clinical management of patients and reduce morbidity and mortality. Objective: One of the constitutional symptoms associated with CRS is fatigue. With the advent of activity tracking digital technology, I propose a pilot study exploring the use of fitness trackers to quantify activity level as a potential predictive biomarker of CRS due to CAR T-Cell immunotherapy. Methods: The proposed study would be a single-arm trial. Patients who are receiving CAR-T Cell immunotherapy will be given a Fitbit Flex 2™ tracker. One week of activity data (measured as steps per day) prior to CAR-T Cell infusion will establish patient baseline activity. From the date of infusion, activity levels will continue to be tracked and analyzed through CRS onset. The patient data will be gathered from Fitbit’s server via a customized app built using Fitbit’s Web Application Programming Interface (API). Results: This is a proposed study. No results have been gathered. Discussion: If a correlation is established between activity levels and onset of CRS, it would enhance the current predictive algorithm, allow easier outpatient management and remote monitoring, decrease costs, and reduce morbidity and mortality

Neighborhoods of trees in circular orderings

In phylogenetics, a common strategy used to construct an evolutionary tree for a set of species X is to search in the space of all such trees for one that optimizes some given score function (such as the minimum evolution, parsimony or likelihood score). As this can be computationally intensive, it was recently proposed to restrict such searches to the set of all those trees that are compatible with some circular ordering of the set X. To inform the design of efficient algorithms to perform such searches, it is therefore of interest to find bounds for the number of trees compatible with a fixed ordering in the neighborhood of a tree that is determined by certain tree operations commonly used to search for trees: the nearest neighbor interchange (nni), the subtree prune and regraft (spr) and the tree bisection and reconnection (tbr) operations. We show that the size of such a neighborhood of a binary tree associated with the nni operation is independent of the tree’s topology, but that this is not the case for the spr and tbr operations. We also give tight upper and lower bounds for the size of the neighborhood of a binary tree for the spr and tbr operations and characterize those trees for which these bounds are attained

Universal Vectorial and Ultrasensitive Nanomechanical Force Field Sensor

Miniaturization of force probes into nanomechanical oscillators enables ultrasensitive investigations of forces on dimensions smaller than their characteristic length scale. Meanwhile it also unravels the force field vectorial character and how its topology impacts the measurement. Here we expose an ultrasensitive method to image 2D vectorial force fields by optomechanically following the bidimensional Brownian motion of a singly clamped nanowire. This novel approach relies on angular and spectral tomography of its quasi frequency-degenerated transverse mechanical polarizations: immersing the nanoresonator in a vectorial force field does not only shift its eigenfrequencies but also rotate eigenmodes orientation as a nano-compass. This universal method is employed to map a tunable electrostatic force field whose spatial gradients can even take precedence over the intrinsic nanowire properties. Enabling vectorial force fields imaging with demonstrated sensitivities of attonewton variations over the nanoprobe Brownian trajectory will have strong impact on scientific exploration at the nanoscale

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis