Oncology Section EDGE Task Force on Urogenital Cancer Outcomes: Clinical Measures of Lymphedema—A Systematic Review

Background: Valid and reliable tools to assess lymphedema are necessary to accurately evaluate status and to objectively document and measure the results of interventions. Understanding the advantages and disadvantages of each measure can inform the clinician\u27s choice of the appropriate tool to be used in the clinic or research setting. Purpose: To identify reliable and valid measurement techniques that are sensitive to change for assessing edema volume or soft tissue change in the lower extremities or genital region of patients with lymphedema. Methods: A systematic review of the literature was conducted to assess the published psychometric properties and clinical feasibility of each method identified. Task Force members independently reviewed each measure using the Cancer EDGE Rating Form. Results: Both water displacement and circumferential measurement methods by tape measure were rated as Highly Recommended to quantify lower-extremity limb volume. Water displacement was determined to be the criterion standard by which all other assessments of volume are benchmarked. Both optoelectric volumetry and bioelectric impedance analysis were rated as Recommended, and ultrasound was rated Not Recommended. Conclusion: The Urogenital Cancer EDGE Task Force highly recommends water displacement and circumferential tape measurement for use as reliable methods for assessment and documentation of change of limb volume in this patient population. Early detection of subclinical lower-extremity lymphedema in this patient population remains challenging, as there is no “index” limb that can be proven to be uninvolved in a patient population with documented pelvic node dissection/irradiation. No articles were found to support valid and reliable genital lymphedema volume measurement

Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection

Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification

Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)) are two critical elements in PCO initiation and progression pathogenesis. While PCO marginally impacts aged cataract surgery patients, PCO incidences are exceptionally high in infants and children undergoing cataract surgery. The gene expression of lens epithelial cell aging and its role in the discrepancy of PCO prevalence between young and older people have not been fully studied. Here, we conducted a comprehensive differentially expressed gene (DEG) analysis of a cell aging model by comparing the early and late passage FHL124 lens epithelial cells (LECs). In vitro, TGFβ2, cell treatment, and in vivo mouse cataract surgical models were used to validate our findings. We found that aged LECs decelerated rates of cell proliferation accompanied by dysregulation of cellular immune response and cell stress response. Surprisingly, we found that LECs systematically downregulated epithelial–mesenchymal transition (EMT)-promoting genes. The protein expression of several EMT hallmark genes, e.g., fibronectin, αSMA, and cadherin 11, were gradually decreased during LECs aging. We then confirmed these findings in vitro and found that aged LECs markedly alleviated TGFβ2-mediated EMT. Importantly, we explicitly confirmed the in vitro findings from the in vivo mouse cataract surgery studies. We propose that both the high proliferation rate and EMT-enriched young LECs phenotypic characteristics contribute to unusually high PCO incidence in infants and children

Cortical Activation Patterns Correlate with Speech Understanding After Cochlear Implantation

OBJECTIVES: Cochlear implants are a standard therapy for deafness, yet the ability of implanted patients to understand speech varies widely. To better understand this variability in outcomes, we used functional near-infrared spectroscopy (fNIRS) to image activity within regions of the auditory cortex and compare the results to behavioral measures of speech perception. DESIGN: We studied 32 deaf adults hearing through cochlear implants and 35 normal-hearing controls. We used fNIRS to measure responses within the lateral temporal lobe and the superior temporal gyrus to speech stimuli of varying intelligibility. The speech stimuli included normal speech, channelized speech (vocoded into 20 frequency bands), and scrambled speech (the 20 frequency bands were shuffled in random order). We also used environmental sounds as a control stimulus. Behavioral measures consisted of the Speech Reception Threshold, CNC words, and AzBio Sentence tests measured in quiet. RESULTS: Both control and implanted participants with good speech perception exhibited greater cortical activations to natural speech than to unintelligible speech. In contrast, implanted participants with poor speech perception had large, indistinguishable cortical activations to all stimuli. The ratio of cortical activation to normal speech to that of scrambled speech directly correlated with the CNC Words and AzBio Sentences scores. This pattern of cortical activation was not correlated with auditory threshold, age, side of implantation, or time after implantation. Turning off the implant reduced cortical activations in all implanted participants. CONCLUSIONS: Together, these data indicate that the responses we measured within the lateral temporal lobe and the superior temporal gyrus correlate with behavioral measures of speech perception, demonstrating a neural basis for the variability in speech understanding outcomes after cochlear implantation

Decoding the memorization of individual stimuli with direct human brain recordings

Contains fulltext : 115385.pdf (Publisher’s version ) (Closed access)Through decades of research, neuroscientists and clinicians have identified an array of brain areas that each activate when a person views a certain category of stimuli. However, we do not have a detailed understanding of how the brain represents individual stimuli within a category. Here we used direct human brain recordings and machine-learning algorithms to characterize the distributed patterns that distinguish specific cognitive states. Epilepsy patients with surgically implanted electrodes performed a working-memory task and we used machine-learning algorithms to predict the identity of each viewed stimulus. We found that the brain's representation of stimulus-specific information is distributed across neural activity at multiple frequencies, electrodes, and timepoints. Stimulus-specific neuronal activity was most prominent in the high-gamma (65-128 Hz) and theta/alpha (4-16 Hz) bands, but the properties of these signals differed significantly between individuals and for novel stimuli compared to common ones. Our findings are helpful for understanding the neural basis of memory and developing brain-computer interfaces by showing that the brain distinguishes specific cognitive states by diverse spatiotemporal patterns of neuronal.10 p