Metastatic Squamous Cell Carcinoma of the Lung Disclosed From Constipation Workup.

A palpable rectal mass associated with gastrointestinal (GI) symptoms immediately raises concern for colorectal cancer, but rarely can represent distant metastatic disease. The incidence of symptomatic colorectal metastasis from a primary lung cancer without any pulmonary symptom is extremely rare. We report a rare case of constipation as the presenting symptom in a patient ultimately found to have metastatic squamous cell carcinoma of the lung. A rectal mass was readily palpable on examination, illustrating the importance of digital rectal examination. In addition, GI clinicians should maintain a high index of suspicion when evaluating patients at risk of non-GI malignancies.

Evidence for a Spoken Word Lexicon in the Auditory Ventral Stream.

The existence of a neural representation for whole words (i.e., a lexicon) is a common feature of many models of speech processing. Prior studies have provided evidence for a visual lexicon containing representations of whole written words in an area of the ventral visual stream known as the visual word form area. Similar experimental support for an auditory lexicon containing representations of spoken words has yet to be shown. Using functional magnetic resonance imaging rapid adaptation techniques, we provide evidence for an auditory lexicon in the auditory word form area in the human left anterior superior temporal gyrus that contains representations highly selective for individual spoken words. Furthermore, we show that familiarization with novel auditory words sharpens the selectivity of their representations in the auditory word form area. These findings reveal strong parallels in how the brain represents written and spoken words, showing convergent processing strategies across modalities in the visual and auditory ventral streams.

A Case of "Anaphylaxis" to NovoSeven in a Hemophiliac Patient.

Anaphylaxis is a life-threatening emergency that may be confused with other less serious conditions. The onset of true anaphylaxis typically occurs within minutes following exposure to an offending agent, and it can variably include dyspnea/wheezing, hemodynamic compromise, rash, hives/pruritus, swelling, or gastrointestinal symptoms. The absence of an expected association between exposure(s) and classic symptoms should lead to the consideration of alternative diagnoses. Here, we describe the course of a patient with hemophilia B who developed stridor and wheezing after exposure to the recombinant factor VII, NovoSeven, and tranexamic acid (TXA) for the management of hematomas. Due to a reported prior history of anaphylaxis to multiple factor replacements, the patient's initial management included NovoSeven with steroid/antihistamine prophylaxes and close monitoring with epinephrine at the bedside. Despite the administration of prophylaxis, the patient developed significant stridor, was treated with epinephrine and nebulizers and additional steroids, and was transferred to the intensive care unit. There, a pattern of NovoSeven administration followed variably by wheezing and stridor continued for two days until the patient's respiratory condition was predictable and stable. The patient's subsequent clinical course following transfer to the general medical ward was not consistent with anaphylaxis. This case highlights the importance of evaluating for mimickers of anaphylaxis, especially where only select symptoms such as stridor and wheezing are present without other serious signs of anaphylaxis such as hypoxemia, hypotension, or significant tachycardia.

Establishment of Host-Algal Endosymbioses: Genetic Response to Symbiont Versus Prey in a Sponge Host.

The freshwater sponge Ephydatia muelleri and its Chlorella-like algal partner is an emerging model for studying animal: algal endosymbiosis. The sponge host is a tractable laboratory organism, and the symbiotic algae are easily cultured. We took advantage of these traits to interrogate questions about mechanisms that govern the establishment of durable intracellular partnerships between hosts and symbionts in facultative symbioses. We modified a classical experimental approach to discern the phagocytotic mechanisms that might be co-opted to permit persistent infections, and identified genes differentially expressed in sponges early in the establishment of endosymbiosis. We exposed algal-free E. muelleri to live native algal symbionts and potential food items (bacteria and native heat-killed algae), and performed RNA-Seq to compare patterns of gene expression among treatments. We found a relatively small but interesting suite of genes that are differentially expressed in the host exposed to live algal symbionts, and a larger number of genes triggered by host exposure to heat-killed algae. The upregulated genes in sponges exposed to live algal symbionts were mostly involved in endocytosis, ion transport, metabolic processes, vesicle-mediated transport, and oxidation-reduction. One of the host genes, an ATP-Binding Cassette transporter that is downregulated in response to live algal symbionts, was further evaluated for its possible role in the establishment of the symbiosis. We discuss the gene expression profiles associated with host responses to living algal cells in the context of conditions necessary for long-term residency within host cells by phototrophic symbionts as well as the genetic responses to sponge phagocytosis and immune-driven pathways.

Steady-State Visually Evoked Potentials and Feature-based Attention: Preregistered Null Results and a Focused Review of Methodological Considerations.

Feature-based attention is the ability to selectively attend to a particular feature (e.g., attend to red but not green items while looking for the ketchup bottle in your refrigerator), and steady-state visually evoked potentials (SSVEPs) measured from the human EEG signal have been used to track the neural deployment of feature-based attention. Although many published studies suggest that we can use trial-by-trial cues to enhance relevant feature information (i.e., greater SSVEP response to the cued color), there is ongoing debate about whether participants may likewise use trial-by-trial cues to voluntarily ignore a particular feature. Here, we report the results of a preregistered study in which participants either were cued to attend or to ignore a color. Counter to prior work, we found no attention-related modulation of the SSVEP response in either cue condition. However, positive control analyses revealed that participants paid some degree of attention to the cued color (i.e., we observed a greater P300 component to targets in the attended vs. the unattended color). In light of these unexpected null results, we conducted a focused review of methodological considerations for studies of feature-based attention using SSVEPs. In the review, we quantify potentially important stimulus parameters that have been used in the past (e.g., stimulation frequency, trial counts) and we discuss the potential importance of these and other task factors (e.g., feature-based priming) for SSVEP studies.

Transdifferentiating Astrocytes Into Neurons Using ASCL1 Functionalized With a Novel Intracellular Protein Delivery Technology.

Cellular transdifferentiation changes mature cells from one phenotype into another by altering their gene expression patterns. Manipulating expression of transcription factors, proteins that bind to DNA promoter regions, regulates the levels of key developmental genes. Viral delivery of transcription factors can efficiently reprogram somatic cells, but this method possesses undesirable side effects, including mutations leading to oncogenesis. Using protein transduction domains (PTDs) fused to transcription factors to deliver exogenous transcription factors serves as an alternative strategy that avoids the issues associated with DNA integration into the host genome. However, lysosomal degradation and inefficient nuclear localization pose significant barriers when performing PTD-mediated reprogramming. Here, we investigate a novel PTD by placing a secretion signal sequence next to a cleavage inhibition sequence at the end of the target transcription factor-achaete scute homolog 1 (ASCL1), a powerful regulator of neurogenesis, resulting in superior stability and nuclear localization. A fusion protein consisting of the amino acid sequence of ASCL1 transcription factor with this novel PTD added can transdifferentiate cerebral cortex astrocytes into neurons. Additionally, we show that the synergistic action of certain small molecules improves the efficiency of the transdifferentiation process. This study serves as the first step toward developing a clinically relevant in vivo transdifferentiation strategy for converting astrocytes into neurons.

Selection criteria for preparatory object rotation in manual lifting actions.

Participants lifted a canister by its handle while balancing a ball on the lid. Experiment 1 allowed object rotation prior to lifting. A lifting comfort zone was measured by the variability in object orientation at lift; its size depended on the object mass and required task precision. The amount of prelift rotation correlated with the resulting change in lifting capability, as measured for different object orientations. Experiment 2 required direct grasping without preparatory rotation. Task completion time and success rate decreased, and initial object orientation affected prelift time. Results suggest that lifting from the comfort zone produces more robust performance at a cost of slower completion; moreover, physical rotation could be replaced by mental planning when direct grasping is enforced.

Method for determining kinematic parameters of the in vivo thumb carpometacarpal joint.

The mobility of the thumb carpometacarpal (CMC) joint is critical for functional grasping and manipulation tasks. We present an optimization technique for determining from surface marker measurements a subject-specific kinematic model of the in vivo CMC joint that is suitable for measuring mobility. Our anatomy-based cost metric scores a candidate joint model by the plausibility of the corresponding joint angle values and kinematic parameters rather than only the marker trajectory reconstruction error. The proposed method repeatably determines CMC joint models with anatomically-plausible directions for the two dominant rotational axes and a lesser range of motion (RoM) for the third rotational axis. We formulate a low-dimensional parameterization of the optimization domain by first solving for joint axis orientation variables that then constrain the search for the joint axis location variables. Individual CMC joint models were determined for 24 subjects. The directions of the flexion--extension (FE) axis and adduction--abduction (AA) axis deviated on average by 9 degrees and 22 degrees , respectively, from the mean axis direction. The average RoM for FE, AA, and pronation--supination (PS) joint angles were 76 degrees , 43 degrees , and 23 degrees for active CMC movement. The mean separation distance between the FE and AA axes was 4.6 mm, and the mean skew angle was 87 degrees from the positive flexion axis to the positive abduction axis.

Robust estimation of dominant axis of rotation.

A simple method is developed for robustly estimating a fixed dominant axis of rotation (AoR) of anatomical joints from surface marker data. Previous approaches which assume a model of circular marker trajectories use plane fitting to estimate the direction of the AoR. However, when there is limited joint range of motion and rotation due to a second degree of freedom, minimizing only the planar error can give poor estimates of the AoR direction. Optimizing a cost function which includes the error component within a plane, instead of only the component orthogonal to a plane, leads to improved estimates of the AoR direction for joints which exhibit additional rotational motion from a second degree of freedom. Results from synthetic data validation show the ranges of motion where the new method has lower estimation error compared to plane-fitting techniques. Estimates of the flexion-extension AoR from empirical motion capture data of the knee and index finger joints were also more anatomically plausible.

Constrained least-squares optimization for robust estimation of center of rotation.

This paper presents a new direct method for estimating the average center of rotation (CoR). An existing least-squares (LS) solution has been shown by previous works to have reduced accuracy for data with small range of motion (RoM). Alternative methods proposed to improve the CoR estimation use iterative algorithms. However, in this paper we show that with a carefully chosen normalization scheme, constrained least-squares solutions can perform as well as iterative approaches, even for challenging problems with significant noise and small RoM. In particular, enforcing the normalization constraint avoids poor fits near plane singularities that can affect the existing LS method. Our formulation has an exact solution, accounts for multiple markers simultaneously, and does not depend on manually-adjusted parameters. Simulation tests compare the method to four published CoR estimation techniques. The results show that the new approach has the accuracy of the iterative methods as well as the short computation time and repeatability of a least-squares solution. In addition, application of the new method to experimental motion capture data of the thumb carpometacarpal (CMC) joint yielded a more plausible CoR location compared to the previously reported LS solution and required less time than all four alternative techniques.

Age-dependent properties and quasi-static strain in the rat sagittal suture.

We measured the morphology of and performed tensile tests on sagittal sutures from rats of postnatal age 2 to 60 days. Using the properties measured ex vivo and a pressure vessel-based analysis, we estimated the quasi-static strain that had existed in the suture in vivo from 2 to 60 days. Sutural thickness, width, and stiffness per length were notable properties found to be age dependent. Sutural thickness increased 4.5-fold (0.11-0.50mm) between 2 and 60 days. Sutural width increased transiently between 2 and 20 days, peaking around 8 days; at 8 days, mean sutural width was 75% larger than mean sutural width at two days (0.35+/-0.07 (SD) vs. 0.20+/-0.06 mm). Sutural stiffness per length increased 4.4-fold (8.77-38.3N/mm/mm) between 2 and 60 days. The quasi-static sutural strain estimated to exist in vivo averaged 270+/-190 muepsilon between 2 and 60 days and was not age dependent. These findings provide data on the age-dependent sutural properties of infant to mature rats and provide the first estimate of quasi-static sutural strain in vivo in the rat. The findings show that during development the rat sagittal suture, as a structure, changes significantly and is exposed to quasi-static tensile strain in vivo due to intracranial pressure.