A panel of clinician scientists with expertise in neuromuscular blockade (NMB) monitoring was convened with a charge to prepare a consensus statement on indications for and proper use of such ...monitors. The aims of this article are to(a) provide the rationale and scientific basis for the use of quantitative NMB monitoring; (b) offer a set of recommendations for quantitative NMB monitoring standards; (c) specify educational goals; and (d) propose training recommendations to ensure proper neuromuscular monitoring and management. The panel believes that whenever a neuromuscular blocker is administered, neuromuscular function must be monitored by observing the evoked muscular response to peripheral nerve stimulation. Ideally, this should be done at the hand muscles (not the facial muscles) with a quantitative (objective) monitor. Objective monitoring (documentation of train-of-four ratio ≥0.90) is the only method of assuring that satisfactory recovery of neuromuscular function has taken place. The panel also recommends that subjective evaluation of the responses to train-of-four stimulation (when using a peripheral nerve stimulator) or clinical tests of recovery from NMB (such as the 5-second head lift) should be abandoned in favor of objective monitoring. During an interim period for establishing these recommendations, if only a peripheral nerve stimulator is available, its use should be mandatory in any patient receiving a neuromuscular blocking drug. The panel acknowledges that publishing this statement per se will not result in its spontaneous acceptance, adherence to its recommendations, or change in routine practice. Implementation of objective monitoring will likely require professional societies and anesthesia department leadership to champion its use to change anesthesia practitioner behavior.
T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8
T cells acquire a distinct epigenetic state, but it is not known whether ...that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we show that the epigenetic state of exhaustion is largely irreversible, even after curative therapy. Analysis of chromatin accessibility in HCV- and HIV-specific responses identifies a core epigenetic program of exhaustion in CD8
T cells, which undergoes only limited remodeling before and after resolution of infection. Moreover, canonical features of exhaustion, including super-enhancers near the genes TOX and HIF1A, remain 'epigenetically scarred.' T cell exhaustion is therefore a conserved epigenetic state that becomes fixed and persists independent of chronic antigen stimulation and inflammation. Therapeutic efforts to reverse T cell exhaustion may require new approaches that increase the epigenetic plasticity of exhausted T cells.
Sex disparities in cardiac homeostasis and heart disease are well documented, with differences attributed to actions of sex hormones. However, studies have indicated sex chromosomes act outside of ...the gonads to function without mediation by gonadal hormones. Here, we performed transcriptional and proteomics profiling to define differences between male and female mouse hearts. We demonstrate, contrary to current dogma, cardiac sex disparities are controlled not only by sex hormones but also through a sex-chromosome mechanism. Using Turner syndrome (XO) and Klinefelter (XXY) models, we find the sex-chromosome pathway is established by X-linked gene dosage. We demonstrate cardiac sex disparities occur at the earliest stages of heart formation, a period before gonad formation. Using these datasets, we identify and define a role for alpha-1B-glycoprotein (A1BG), showing loss of A1BG leads to cardiac defects in females, but not males. These studies provide resources for studying sex-biased cardiac disease states.
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•Sex hormones and sex-chromosome mechanisms contribute to cardiac sex disparities•Sex-chromosome pathway in the heart is established by X-linked gene dosage•Cardiac sex disparities occur before sex gonad formation•Loss of A1BG leads to cardiac defects in females, but not in males
Male/female differences in cardiac function and disease have been attributed to hormonal differences. In this paper, though transcriptomic and proteomic analyses in mice, Shi et al. find that cardiac differences first appear in embryos prior to gonad formation, suggesting a sex-chromosome-dependent mechanism.
Smallpox was the most rampant infectious disease killer of the 20th century, yet much remains unknown about the pathogenesis of the variola virus. Using archived tissue from a study conducted at the ...Centers for Disease Control and Prevention we characterized pathology in 18 cynomolgus macaques intravenously infected with the Harper strain of variola virus. Six macaques were placebo-treated controls, six were tecovirimat-treated beginning at 2 days post-infection, and six were tecovirimat-treated beginning at 4 days post-infection. All macaques were treated daily until day 17. Archived tissues were interrogated using immunohistochemistry, in situ hybridization, immunofluorescence, and electron microscopy. Gross lesions in three placebo-treated animals that succumbed to infection primarily consisted of cutaneous vesicles, pustules, or crusts with lymphadenopathy. The only gross lesions noted at the conclusion of the study in the three surviving placebo-treated and the Day 4 treated animals consisted of resolving cutaneous pox lesions. No gross lesions attributable to poxviral infection were present in the Day 2 treated macaques. Histologic lesions in three placebo-treated macaques that succumbed to infection consisted of proliferative and necrotizing dermatitis with intracytoplasmic inclusion bodies and lymphoid depletion. The only notable histologic lesion in the Day 4 treated macaques was resolving dermatitis; no notable lesions were seen in the Day 2 treated macaques. Variola virus was detected in all three placebo-treated animals that succumbed to infection prior to the study's conclusion by all utilized methods (IHC, ISH, IFA, EM). None of the three placebo-treated animals that survived to the end of the study nor the animals in the two tecovirimat treatment groups showed evidence of variola virus by these methods. Our findings further characterize variola lesions in the macaque model and describe new molecular methods for variola detection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving ...immunotherapeutic modalities. Here we confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8
T cells in human hepatitis C virus (HCV) infection before and after treatment. After viral cure, phenotypic changes in clonally stable exhausted T cell populations suggested differentiation toward a memory-like profile. However, functionally, the cells showed little improvement, and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for less time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved HCV infection. Thus, the duration of T cell stimulation impacts exhaustion recovery, with antigen removal after long-term exhaustion being insufficient for the development of functional T cell memory.
Objective
Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an ...alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM‐induced seizures (EISs) between the two electrode types.
Methods
Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates.
Results
We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication.
Significance
SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.
We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography SEEG and subdural electrodes SDE), and electrical ...stimulation mapping (ESM) of speech/language.
Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM.
Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores.
Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.
There is tremendous diversity of interactions between plants and other species. These relationships range from antagonism to mutualism. Interactions of plants with members of their ecological ...community can lead to a profound metabolic reconfiguration of the plants’ physiology. This reconfiguration can favour beneficial organisms and deter antagonists like pathogens or herbivores. Determining the cellular and molecular dialogue between plants, microbes, and insects, and its ecological and evolutionary implications is important for understanding the options for each partner to adopt an adaptive response to its biotic environment. Moving forward, understanding how such ecological interactions are shaped by environmental change and how we potentially mitigate deleterious effects will be increasingly important. The development of integrative multidisciplinary approaches may provide new solutions to the major ecological and societal issues ahead of us. The rapid evolution of technology provides valuable tools and opens up novel ways to test hypotheses that were previously unanswerable, but requires that scientists master these tools, understand potential ethical problems flowing from their implementation, and train new generations of biologists with diverse technical skills. Here, we provide brief perspectives and discuss future promise and challenges for research on insect–plant interactions building on the 16th International Symposium on Insect–Plant interactions (SIP) meeting that was held in Tours, France (2–6 July 2017). Talks, posters, and discussions are distilled into key research areas in insect–plant interactions, highlighting the current state of the field and major challenges, and future directions for both applied and basic research.
There is tremendous diversity of interactions between plants and other species, ranging from antagonism to mutualism. Determining the cellular and molecular dialogue between plants, microbes, and insects, and its ecological and evolutionary implications is important. Integrative multidisciplinary approaches and the rapid evolution of technology may provide new solutions to the major ecological and societal issues ahead of us. This article reviews the major ground‐breaking themes that have been identified as promising and challenging issues in studies on insect–plant interactions.
Objectives: Choanal atresia (CA) is a congenital obstruction of the posterior nasal apertures. Multiple surgical techniques have been proposed to repair the atresia. The purpose of this study is to ...review the basic science and embryology of CA with emphasis on the senior author's extensive experience, and refinement of the treatment of CA. In addition, we will review the outcomes after surgical correction of pediatric patients with CA.
Patients and Methods: Retrospective review of 73 pediatric patients. Demographic information was recorded, including type of CA, concomitant medical problems, surgical method, and date of last follow‐up by the surgeon.
Results: Our series show a 1.6:1 ratio of unilateral atresia to bilateral atresia. The incidence in males and females is statistically equal. High‐arched palate and cross‐bite deformities are particularly present if the patients undergo the transpalatal approach in the first year of life. The senior author has evolved to favoring the endoscopic approach, having a minimal long‐term complication rate, and low stenosis rate (12%).
Conclusions: The first repair of choanal atresia is the one most likely to succeed. The nasal endoscopic technique is the favored technique. It has the advantages of a low restenosis rate, does not violate the palate, and does not cause the cross‐bite and palate arch deformities seen in the transpalatal technique.
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