Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of twitch transdiaphragmatic, esophageal, and endotracheal tube pressure with bilateral anterolateral magnetic phrenic nerve stimulation in patients in the intensive care unit

ObjectiveIn the critically ill, respiratory muscle strength usually has been assessed by measuring maximum inspiratory pressure. The maneuver is volitional, and results can be unreliable. The nonvolitional technique of bilateral anterolateral magnetic stimulation of the phrenic nerves, producing twitch transdiaphragmatic pressure, has been successful in normal subjects and ambulatory patients. In this study we used the technique in the intensive care unit and explored the measurement of twitch endotracheal tube pressure as a less invasive technique to assess diaphragmatic contractility. DesignClinical study to quantify diaphragm strength in the intensive care unit. SettingPatients from three London teaching hospital intensive care units and high-dependency units. PatientsForty-one intensive care patients were recruited. Of these, 33 (20 men, 13 women) were studied. InterventionsEsophageal and gastric balloon catheters were passed through the anaesthetized nose, and an endotracheal tube occlusion device was placed in the ventilation circuit, next to the endotracheal tube. Two 43-mm magnetic coils were placed anteriorly on the patient’s neck, and the phrenic nerves were stimulated magnetically. Measurements and Main Results On phrenic nerve stimulation, twitch gastric pressure, twitch esophageal pressure, twitch transdiaphragmatic pressure, and twitch endotracheal tube pressure were measured. Forty-one consecutive patients consented to take part in the study, and twitch pressure data were obtained in 33 of these. Mean transdiaphragmatic pressure was 10.7 cm H2O, mean twitch esophageal pressure was 6.7 cm H2O, and mean twitch endotracheal tube pressure was 6.7 cm H2O. The mean difference between twitch esophageal pressure and twitch endotracheal tube pressure was 0.02 cm H2O. Correlation of the means of twitch endotracheal tube pressure to twitch esophageal pressure was 0.93, and that for twitch endotracheal tube pressure to transdiaphragmatic pressure was 0.78. ConclusionsTransdiaphragmatic pressure can be measured in the critically ill to give a nonvolitional assessment of diaphragm contractility, but not all patients can be studied. At present, the relationship of twitch endotracheal tube pressure to transdiaphragmatic pressure is too variable to reliably represent a less invasive measure of diaphragm strength.
Inference of Functional Properties from Large-scale Analysis of Enzyme Superfamilies*

As increasingly large amounts of data from genome and other sequencing projects become available, new approaches are needed to determine the functions of the proteins these genes encode. We show how large-scale computational analysis can help to address this challenge by linking functional information to sequence and structural similarities using protein similarity networks. Network analyses using three functionally diverse enzyme superfamilies illustrate the use of these approaches for facile updating and comparison of available structures for a large superfamily, for creation of functional hypotheses for metagenomic sequences, and to summarize the limits of our functional knowledge about even well studied superfamilies.
Photoreceptor Signaling: Supporting Vision across a Wide Range of Light Intensities*

For decades, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and biochemistry and for understanding many facets of neuronal cell biology. In recent years, new knowledge of the kinetics of signaling and the large-scale movements of proteins underlying signaling has led to a deeper appreciation of the photoreceptor's unique challenge in mediating the first steps in vision over a wide range of light intensities.
Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion*

Lipid droplets (LDs) are organelles found in most types of cells in the tissues of vertebrates, invertebrates, and plants, as well as in bacteria and yeast. They differ from other organelles in binding a unique complement of proteins and lacking an aqueous core but share aspects of protein trafficking with secretory membrane compartments. In this minireview, we focus on recent evidence supporting an endoplasmic reticulum origin for LD formation and discuss recent findings regarding LD maturation and fusion.
Sirtuin Catalysis and Regulation*

Sirtuins are a family of NAD+-dependent protein deacetylases/deacylases that dynamically regulate transcription, metabolism, and cellular stress response. Their general positive link with improved health span in mammals, potential regulation of pathways mediated by caloric restriction, and growing links to human disease have spurred interest in therapeutics that target their functions. Here, we review the current understanding of the chemistry of catalysis, biological targets, and endogenous regulation of sirtuin activity. We discuss recent efforts to generate small-molecule regulators of sirtuin activity.
A molecular approach to self-supported cobalt-substituted ZnO materials as remarkably stable electrocatalysts for water oxidation.

In regard to earth-abundant cobalt water oxidation catalysts, very recent findings show the reorganization of the materials to amorphous active phases under catalytic conditions. To further understand this concept, a unique cobalt-substituted crystalline zinc oxide (Co:ZnO) precatalyst has been synthesized by low-temperature solvolysis of molecular heterobimetallic Co(4-x)Zn(x) O4 (x = 1-3) precursors in benzylamine. Its electrophoretic deposition onto fluorinated tin oxide electrodes leads after oxidative conditioning to an amorphous self-supported water-oxidation electrocatalyst, which was observed by HR-TEM on FIB lamellas of the EPD layers. The Co-rich hydroxide-oxidic electrocatalyst performs at very low overpotentials (512 mV at pH 7; 330 mV at pH 12), while chronoamperometry shows a stable catalytic current over several hours.
Detection by Bioassay and Specific Enzyme‐Linked Immunosorbent Assay of Phosphoramidon‐Inhibitable Endothelin‐Converting Activity in Brain and Endothelium

Summary: The endothelin‐converting enzyme (ECE) activity present in endothelial cells and rat and human brains was characterized using a selective and rapid bioassay for endothelin‐1 (ET‐1) or endothelin‐3 (ET‐3) together with a sensitive enzyme‐linked immunosorbent assay. We found that ECE activity was predominantly in the membrane fraction of endothelial cells from which it could be extracted by treatment with detergent. In rat brain tissue, the ECE activity was in the membrane fraction and was not solubilized by detergent treatment. Further dissection of the brain revealed that there was a strong localization of ECE activity in the hypothalamus, midbrain, and medulla oblongata in agreement with earlier observations of ET‐like immunoreactivity and binding sites. Experiments with human brain tissue also showed the presence of ECE activity. In conclusion, our studies confirmed the presence of ECE activity within endothelial cells, and showed ECE to be localized in brain tissue in sites consistent with the selective distribution of the ET‐1 synthetic pathway. In all tissues studied, the ECE activity was significantly inhibited by phosphoramidon or ethylenediaminetetra‐acetate.
Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target*

Work over the past 4 years indicates that multiple proteins associated with neurodegenerative diseases, especially Tau and α-synuclein, can propagate aggregates between cells in a prion-like manner. This means that once an aggregate is formed it can escape the cell of origin, contact a connected cell, enter the cell, and induce further aggregation via templated conformational change. The prion model predicts a key role for extracellular protein aggregates in mediating progression of disease. This suggests new therapeutic approaches based on blocking neuronal uptake of protein aggregates and promoting their clearance. This will likely include therapeutic antibodies or small molecules, both of which can be developed and optimized in vitro prior to preclinical studies.
Metal Preferences and Metallation

The metal binding preferences of most metalloproteins do not match their metal requirements. Thus, metallation of an estimated 30% of metalloenzymes is aided by metal delivery systems, with ∼25% acquiring preassembled metal cofactors. The remaining ∼70% are presumed to compete for metals from buffered metal pools. Metallation is further aided by maintaining the relative concentrations of these pools as an inverse function of the stabilities of the respective metal complexes. For example, magnesium enzymes always prefer to bind zinc, and these metals dominate the metalloenzymes without metal delivery systems. Therefore, the buffered concentration of zinc is held at least a million-fold below magnesium inside most cells.
Writing and Reading the Tubulin Code*

Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with cellular regulators. These modifications are important for the biogenesis and maintenance of complex microtubule arrays such as those found in spindles, cilia, neuronal processes, and platelets. Here we discuss the nature and subcellular distribution of these posttranslational marks whose patterns have been proposed to constitute a tubulin code that is interpreted by cellular effectors. We review the enzymes responsible for writing the tubulin code, explore their functional consequences, and identify outstanding challenges in deciphering the tubulin code.
Experience with the Temporoparietal Fascial Free Flap

The temporoparietal fascia is an ideal tissue source for free transfer to distant sites where ultrathin coverage is either desirable or mandatory. The fascia's dependable vascular anatomy facilitates the technical aspects of microvascular transfer by means of its large vessels, ample pedicle, and ability to be grafted on either side. Furthermore, this highly vascular tissue is available in surprisingly large quantities, and its donor scar is hidden in the hair. The authors have found this flap useful (1) in covering exposed bone and tendon without adding unwanted bulk, (2) in providing thin flap coverage or lining in major facial reconstruction, (3) in covering vital structures such as exposed nerves and vessels, (4) in providing neovascularity both as a recipient graft bed and for control of chronic infection, and (5) in reestablishing gliding-tendon mechanisms. The authors have successfully employed this free flap in 15 cases which involved deformities of the ankle, foot, Achilles tendon, forearm, hand, nose, and contralateral ear and scalp. Seven cases are utilized to illustrate the broad application of this unique and versatile free flap.
Physiological Consequences of Compartmentalized Acyl-CoA Metabolism*

Meeting the complex physiological demands of mammalian life requires strict control of the metabolism of long-chain fatty acyl-CoAs because of the multiplicity of their cellular functions. Acyl-CoAs are substrates for energy production; stored within lipid droplets as triacylglycerol, cholesterol esters, and retinol esters; esterified to form membrane phospholipids; or used to activate transcriptional and signaling pathways. Indirect evidence suggests that acyl-CoAs do not wander freely within cells, but instead, are channeled into specific pathways. In this review, we will discuss the evidence for acyl-CoA compartmentalization, highlight the key modes of acyl-CoA regulation, and diagram potential mechanisms for controlling acyl-CoA partitioning.
Cold acclimation induces rapid and dynamic changes in freeze tolerance mechanisms in the cryophile Deschampsia antarctica E. Desv.

The cryophilic Antarctic hair grass, Deschampsia antarctica E. Desv. , one of two higher plants indigenous to Antarctica, represents a unique resource for the study of freeze tolerance mechanisms. We have previously characterized a multi-gene family in D. antarctica encoding ice recrystallization inhibition proteins (IRIPs) whose transcript levels are responsive to cold acclimation, and whose products confer ice recrystallization inhibition (RI) activity that can account for activity seen in cold acclimated plants. We used molecular and physiological analyses to investigate temporal responses of D. antarctica to cold acclimation and de-acclimation, and sub-zero acclimation. Quantitative profiling revealed that IRIP transcript levels significantly increased and decreased within hours of cold acclimation and de-acclimation, respectively, becoming up to 1000-fold more abundant in fully acclimated plants. Western analysis detected three major immuno-reactive bands whose pattern of accumulation mirrored that of transcript. These data correlated with the onset and decline of RI activity in acclimated and de-acclimated leaves. Plant survival-based testing revealed that cold acclimation enhanced freeze tolerance by 5 °C within 4 d, and that sub-zero acclimation conferred an additional 3 °C of tolerance. Thus, D. antarctica is highly responsive to temperature fluctuations, able to rapidly deploy IRIP based RI activity and enhance its freeze tolerance.
PSYCHOLOGIC TESTS APPLIED TO DIABETIC PATIENTS

Diabetes is well known to exert an important influence on the central nervous system. Kraus1recently summarized the more common neurologic lesions, and the psychoses occasionally associated with diabetes have been the subject of numerous studies. The diabetic patient, on his own part, complains of loss of memory and of poor ability to concentrate the attention. So far as we are aware, there are no objective data which either substantiate or contradict this clinical picture in reference to attention and memory. We have undertaken to gain some light as to the extent of the impairment if such exists, comparing diabetic patients as a group with controls who are of about the same mental status. METHOD At the New England Deaconess Hospital in Boston, Dr. E. P. Joslin has for some years conducted twice a week a patients' class in diabetic hygiene. We took advantage of meetings of this class which
Ribose-protonated DNA base excision repair: a combined theoretical and experimental study.

Living organisms protect the genome against external influences by recognizing and repairing damaged DNA. A common source of gene mutation is the oxidized guanine, which undergoes base excision repair through cleavage of the glycosidic bond between the ribose and the nucleobase of the lesion. We unravel the repair mechanism utilized by bacterial glycosylase, MutM, using quantum-chemical calculations involving more than 1000 atoms of the catalytic site. In contrast to the base-protonated pathway currently favored in the literature, we show that the initial protonation of the lesion's ribose paves the way for an almost barrier-free glycosidic cleavage. The combination of theoretical and experimental data provides further insight into the selectivity and discrimination of MutM's binding site toward various substrates.
Cardiovascular , Pulmonary , and Renal Pathology Respiratory and Olfactory Cytotoxicity of Inhaled 2 , 3-Pentanedione in Sprague-Dawley Rats

Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the -diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another -diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9—318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione–metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain. (Am J Pathol 2012, 181:829–844; http://dx.doi.org/10.1016/j.ajpath.2012.05.021)
In situ quantification and visualization of lithium transport with neutrons.

A real-time quantification of Li transport using a nondestructive neutron method to measure the Li distribution upon charge and discharge in a Li-ion cell is reported. By using in situ neutron depth profiling (NDP), we probed the onset of lithiation in a high-capacity Sn anode and visualized the enrichment of Li atoms on the surface followed by their propagation into the bulk. The delithiation process shows the removal of Li near the surface, which leads to a decreased coulombic efficiency, likely because of trapped Li within the intermetallic material. The developed in situ NDP provides exceptional sensitivity in the temporal and spatial measurement of Li transport within the battery material. This diagnostic tool opens up possibilities to understand rates of Li transport and their distribution to guide materials development for efficient storage mechanisms. Our observations provide important mechanistic insights for the design of advanced battery materials.
A Comparison of the Society of Thoracic Surgeons and EuroSCORE Risk Stratification Models in Predicting Mortality in a US Cohort: P19

Background The STS algorithm was developed to predict mortality for US patients undergoing cardiac surgery. In Europe a different model has been developed the EuroSCORE. These algorithms are used daily in risk-stratification of patients for surgery and risk-adjustment. We sought to determine and compare the discriminatory ability of the scoring systems within a US cohort. Methods Between January 1, 2002 and September 1 2004, 1408 CABG and 429 valve patients were operated upon between January 1, 2002 and September 1 2004. Risk factors were entered prospectively into a local adult cardiac surgery database. Observed 30-day mortality and the calculated predicted 30-day mortality for 3 risk prediction models (STS algorithm, additive EuroSCORE and logistic EuroSCORE) were compared within the 2 patient groups. The decriminatory powers of the models were assessed by calculating the areas under receiver operating characteristics (ROC) curves. An area of 1.0 represents perfect discrimination and an area of 0.50 indicates no discrimination. Results In CABG procedures the area under the ROC curve was 0.83 (95%CI 0.79–0.87) for STS, 0.75 (95%CI 0.70–0.80) for additive EuroSCORE and 0.76 (95%CI 0.71–0.81) for logistic EuroSCORE. In valve procedures the area under the ROC curve was 0.79 (95%CI 0.70–0.87) for STS, 0.64 (95%CI 0.56–0.72) for additive EuroSCORE and 0.64 (95%CI 0.56–0.72) for logistic EuroSCORE. Conclusions All risk algorithms have good predictive power in ascertaining 30-day mortality in CABG patients. The STS algorithm out-performed its European equivalents in both CABG and valve surgery. We can use the STS algorithm with confidence ensuring quality of care is maintained.
A communicable disease network in Italy

Communicable disease surveillance systems do not always provide accurate or timely data. Furthermore, in Italy, data entry and management are only performed centrally, making the completion of missing data and an improvement in the quality of data difficult to realize. To improve this system, the Istituto Superiore di Sanita conducted a pilot trial in the region of Tuscany. The trial consisted of creating a network of persons responsible for surveillance in the region, conducting training courses in surveillance and implementing an ad hoc computerized system for the management, transmission and rapid analysis of notifications. Standardized notification forms were computerized with Epilnfo 5.0 software with quality control programmes. The system also provided printouts with individual and aggregated case report forms. The data were transmitted using an existing national network. A set of standard tables was included in the monthly regional epidemiologic bulletin for information feedback to the local health staff. Following its implementation, the percentage of notified cases with errors in the diagnostic criteria reported for case definitions decreased from 2.8 (95% Cl: 0.8–4.8) to 0.15% and individual data were centrally available on magnetic support two months after the notification date (compared to 3–4 years delay previously). We also witnessed an overall improvement in the timeliness and quality of routine notification. To create an effective national disease surveillance network, it would be beneficial to extend the system described in this pilot trial to all regions of Italy.
Natural history of HIV-control since seroconversion

Objectives:HIV-controllers spontaneously maintain HIV viremia at an undetectable level. We aimed to describe the delay to control from seroconversion, the duration of control, and risk factors for losing control. Methods:HIV-controllers were identified from a pooled dataset of 24 seroconverter cohorts from Europe, Australia, and Canada (CASCADE). HIV-controllers had at least five consecutive viral loads less than 400/500 copies/ml, while antiretroviral therapy naive, for at least 5 years after seroconversion. End of control was defined as two consecutive viral loads above 2000 copies/ml. Duration of control was described using Kaplan–Meier estimates; factors associated with duration of control were identified using a Cox model. CD4+ cell count evolution during control was described using a mixed model. Results:Of 9896 eligible seroconverters, we identified 140 (1.4%) HIV-controllers, the largest database of HIV-controllers followed from seroconversion. For 64 with viral load measured within 24 months from seroconversion, median delay to control was 16.7 (interquartile range: 7.8–37.9) months. Probability of maintaining control 20 years after seroconversion was 0.74 [95% confidence interval (CI): 0.64–0.85]. Occurrence of blips followed by return to undetectability did not increase the risk of loss of control [hazard ratio: 0.81 (95% CI: 0.10–6.70)]. However, CD4+ cell loss during control was significantly accelerated in individuals with blips. Conclusion:In most individuals, control occurred rapidly after seroconversion; however, more than 3 years were required to achieve control in 25% of HIV-controllers. Control may be sustained even when CD4+ cell levels are below 500 cells/&mgr;l, opening important new perspectives to understand the physiopathology underlying control.