Miracle-dz/UniFAR-FTUs huggingface dataset:
Do standard monitoring sites affect true brain temperature when hyperthermia is rapidly induced and reversed.

BACKGROUND Accurate measurements of brain and core temperatures during warming and cooling of the whole organism, accidentally or therapeutically, are important for studies of thermoregulation and cerebral insults and resuscitation. HYPOTHESIS During steady states and normal circulation, temperatures in the brain, nasopharynx, esophagus and rectum (the latter are core temperatures) equilibrate quickly; and that during rapid cooling or warming, slight temperature gradients occur, with esophageal core temperature reflecting brain temperature better than rectal temperature. METHODS We evaluated 5 mongrel dogs and 12 pigtail monkeys. The animals were exposed to total body hyperthermia by immersion into water at 45 degrees C to achieve cerebral temperature 42 degrees C which was maintained until cardiac arrest. In monkeys, at cardiac arrest, surface cooling and cardiopulmonary resuscitation were attempted for up to 30 min to determine resuscitability at 38.5 degrees C. Continuously monitored were brain (epidural) (Tep), esophageal (Tes), rectal (Tre) and nasopharyngeal temperatures (Tnp). Also monitored were mean arterial pressure and intracranial pressure. RESULTS At normothermia, in dogs and monkeys, Tep, Tre, Tes and Tnp correlated well. In the dogs, during heating, Tes, Tnp and Tre at first correlated well. Vigorous panting started as Tep reached 41 degrees C, which immediately lowered Tnp and Tep to increase less steeply than Tes and Tre. After about 40 min of panting, with cerebral perfusion pressure still normal, Tep decreased sharply and reached the levels of Tnp, while Tre remained high. In the monkeys during heating, Tep, Tes and Tre correlated well. When cerebral perfusion pressure decreased below 50 mmHg, Tep declined significantly as compared with Tre, which continued to be high in severe arterial hypotension. Tes at that time achieved levels between Tep and Tre. During cooling in monkeys, the decline in Tre was slower as compared with the decline in Tes and Tep. CONCLUSIONS In normal dogs and monkeys, rectal, esophageal and nasopharyngeal temperatures are almost identical with brain temperatures; but during rapid external warming or cooling, brain temperature is reflected in nasopharyngeal temperature, somewhat in higher esophageal temperature, but not in even higher rectal temperature. For clinical monitoring during temperature changes, one should use primarily esophageal temperature and, if feasible, brain (epidural) temperature as well.
A Java platform for the implementation of the finite-difference time-domain method

This paper presents an implementation of the finite-difference time-domain (FD-TD) method in Java using CPML boundary conditions. The FD-TD code was validated with a canonical problem. The performance of the Java code was tested in half wavelength dipole in a 3D domain containing bone and brain. The results indicate that Java is appropriate for this kind of calculation due to its several advantages and for being significantly faster than Matlab with the same accuracy.
Region‐specific age effects on AMPA sensitivity: Electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1

The effects of aging on the responsiveness of hippocampal neurons to iontophoretic application of L‐glutamate and AMPA were studied in vitro. There were no effects of age on neuronal responses to L‐glutamate; however, CA1 pyramidal cells of old rats, but not granule cells in the fascia dentata, showed both a smaller reduction in extracellularly‐recorded synaptic responses following application of AMPA (presumably mediated by depolarization), and smaller extracellular “DC” fields (measured by subtracting the DC potentials at the dendrite and soma following AMPA application in the dendrites). To examine the cellular bases of this age‐related alteration in AMPA sensitivity, two additional electrophysiological approaches were used: (1) measurement of the amplitude ratios of extracellular EPSP and fiber potential components of the Schaffer collateral‐CA1 response; (2) measurement of intracellularly recorded unitary EPSPs and quantal analysis of their fluctuations. The interpretations that would be placed on four hypothetical possible outcomes of such experiments are outlined and assessed in relation to the experimental data. The pattern of results obtained in the present experiments supports the following conclusions: In old rats, individual Schaffer collateral synapses do not appear to have altered AMPA receptor properties, as neither the mean size of the unitary synaptic response nor the apparent quantal size differs between age groups; however, the data do support the conclusion that there are fewer synapses per Schaffer collateral branch in old versus young CA1 pyramidal cells.
When Cardiac Failure, Kidney Dysfunction, and Kidney Injury Intersect in Acute Conditions: The Case of Cardiorenal Syndrome

Objective:To review and describe diagnostic and prognostic value of biomarkers of renal function and renal injury in the cardiorenal syndrome complicating acutely decompensated heart failure. Data Sources:PubMed search and review of relevant medical literature. Study Selection:Two reviewers screened and selected studies in English with diagnostic or prognostic assessment of biomarkers of renal injury. Data Extraction:Narrative review of the medical literature. Data Synthesis:Cardiorenal syndrome has a complex pathophysiology and has a generally poor prognosis in patients with acutely decompensated heart failure. Among the methods to recognize risk for cardiorenal syndrome may be the use of circulating or urinary biomarkers, which may allow for more accurate early diagnosis and risk stratification; use of biomarkers may provide important pathophysiologic understanding beyond risk prediction. However, different phenotypes of patients with acute renal dysfunction may be present, which has ramifications with respect to response to treatment strategies. Addition of biomarkers of renal injury may provide additional prognostic value to biomarkers of renal or cardiac function, but more data are needed. Conclusions:Biomarkers reflecting renal function and injury are likely to better phenotype subgroups of patients with cardiorenal syndrome and to provide unique prognostic information. Future studies are needed relative to strategies using such biomarkers to guide care of affected patients.
Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP‐treated common marmosets

l‐3,4‐dihydroxyphenylalanine methyl ester (l‐DOPA)‐induced dyskinesia in Parkinson's disease may result from aberrant glutamatergic stimulation of the striatum due to synaptic plasticity in the motor cortex or striatum as a consequence of adaptation of striatal output pathways. This might result from changes in NMDA receptor subunit or NMDA receptor associated postsynaptic density (PSD) scaffold protein expression. Using immunoautoradiography the expression levels of NR1 and NR2B subunits of the NMDA receptor and the postsynaptic density scaffold proteins, PSD‐95, PSD‐93, and neurofilament light (NFL) were examined in normal common marmosets (Callithrix jacchus) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐lesioned animals that exhibited high or low levels of l‐DOPA‐induced dyskinesia. Brains from MPTP‐lesioned animals that were not primed for l‐DOPA‐induced dyskinesia were not included in this study. No alterations in the NR1 NMDA receptor subunit were observed. The NR2B NMDA receptor subunit was increased in caudal caudate nucleus and putamen, hippocampus, cingulate motor area (CMA), supplementary motor area (SMA) and dorsal primary motor cortex (dMI) of highly dyskinetic MPTP‐lesioned marmosets, but not in animals with low levels of dyskinesia. PSD‐93 was decreased in the globus pallidus of marmosets with high and low levels of dyskinesia and increased in the CMA, SMA and dMI of highly dyskinetic marmosets. PSD‐95 was increased in the SMA of highly dyskinetic marmosets, but not in animals with low dyskinesia. NFL expression was elevated in the SMA and dorsal and ventral MI of highly dyskinetic marmosets. These results suggest that l‐DOPA treatment of MPTP‐lesioned marmosets can affect glutamatergic systems and indicate that altered NMDA receptor function may relate to dyskinesia.
Hyperhomocysteinemia Is Related to Residual Glomerular Filtration and Folate, but not to Methylenetetrahydrofolate-Reductase and Methionine Synthase Polymorphisms, in Supplemented End-Stage Renal Disease Patients Undergoing Hemodialysis

Abstract Glomerular filtration is one of the major determinants of plasma total homocysteine (tHcy). To evaluate the respective roles of residual glomerular filtration (by measuring a specific protein marker, cystatin C), genetic polymorphisms and nutritional status in tHcy blood levels in end-stage renal disease patients (ESRD) under hemodialysis and supplemented with folate, we measured tHcy, folate, vitamin B12 (B12), creatinine, cystatin C, albumin and C-reactive protein and determined the polymorphism of methylenetetrahydrofolate reductase (MTHFR) (C677T and A1289C) and of methionine synthase (MS) (A2756G) in 114 ESRD patients before hemodialysis and 76 control subjects. All patients received a folate supplementation of 700 μg/day. Hyperhomocysteinemia was observed in all patients and exceeded the upper normal limit by 2-fold in 52.4% of the patients. Serum folate was significantly increased and the B12 level was not different from controls. Folate, Cystatin C and creatinine were significantly correlated to tHcy, while no correlation was found between tHcy, albumin and C-reactive protein. No difference in genotype frequency between ESRD patients and controls was found for MTHFR A1289C and MS A2756G. The MTHFR 677TT genotype was less frequent and was associated with a significantly higher tHcy level in patients. Folate and residual glomerular filtration estimated by cystatin C and creatinine levels were two independent determinants of tHcy in ESRD patients. These data suggest that hyperhomocysteinemia is a consequence as well as a complicating factor of renal failure.
Variation of Hepatic Methotrexate 7‐Hydroxylase Activity in Animals and Humans

This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7‐hydroxymethotrexate in animals and humans. When MTX 7‐hydroxylase was assayed in six human liver cytosols, a 48‐fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate. Species differences of liver MTX 7‐hydroxylase activity were also observed. The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7‐hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX 7‐hydroxylase in livers of animals and humans, and the observed differences of MTX 7‐hydroxylase activity are due to variations in the amount of aldehyde oxidase present.
Mixed Carboxylic Acid Production by Megasphaera elsdenii from Glucose and Lignocellulosic Hydrolysate

Volatile fatty acids (VFAs) can be readily produced from many anaerobic microbes and subsequently utilized as precursors to renewable biofuels and biochemicals. Megasphaera elsdenii represents a promising host for production of VFAs, butyric acid (BA) and hexanoic acid (HA). However, due to the toxicity of these acids, product removal via an extractive fermentation system is required to achieve high titers and productivities. Here, we examine multiple aspects of extractive separations to produce BA and HA from glucose and lignocellulosic hydrolysate with M. elsdenii. A mixture of oleyl alcohol and 10% (v/v) trioctylamine was selected as an extraction solvent due to its insignificant inhibitory effect on the bacteria. Batch extractive fermentations were conducted in the pH range of 5.0 to 6.5 to select the best cell growth rate and extraction efficiency combination. Subsequently, fed-batch pertractive fermentations were run over 230 h, demonstrating high BA and HA concentrations in the extracted fraction (57.2 g/L from ~190 g/L glucose) and productivity (0.26 g/L/h). To our knowledge, these are the highest combined acid titers and productivity values reported for M. elsdenii and bacterial mono-cultures from sugars. Lastly, the production of BA and HA (up to 17 g/L) from lignocellulosic sugars was demonstrated.
Prenatal effects of betamethasone-L-carnitine combinations on fetal rat lung

Lungs of fetal rats between the 18th and 20th gestational day (total gestation lasting 22 days) were examined. There was a significant increase (p < 0.01) of the dipalmitoyl phosphatidylcholine content from day 19 to day 20 of gestation. In the second trial, pregnant rats were treated with different doses of betamethasone, L-carnitine, betamethasone-L-carnitine combinations, and saline (controls) for three days before Cesarean section on the 19th gestational day. Maternal injections of 0.10 mg/kg body weight betamethasone and 100 mg/kg body weight L-carnitine significantly (p < 0.05, p < 0.01 respectively) increased the dipalmitoyl phosphatidylcholine content of fetal lungs. Combinations of either 0.05 or 0.10 mg/kg body weight betamethasone with 100 mg L-carnitine also significantly increased the dipalmitoyl phosphatidylcholine content of the fetal lungs above control values (p < 0.001) and values achieved with betamethasone alone (p < 0.05). Maternal treatment with a betamethasone-L-carnitine combination on day 19 of gestation resulted in dipalmitoyl phosphatidylcholine levels comparable to those found on the 20th gestational day during normal lung maturation. Fetal rats delivered on the 20th gestational day survived, while fetuses delivered on the 19th gestational day did not survive.
Central and Peripheral Corneal Thinning in Keratoconus

Purpose: Recent data regarding the mid-peripheral portion of the removed corneal button in transplant surgery indicate histopathologically that keratoconus was present also in the peripheral portion of the button. The intent of this study was therefore to investigate if peripheral changes could also be detected clinically by measuring the central and peripheral corneal thickness of KC patients. Methods: Corneal pachymetry was measured with the Visante optical coherence tomography and Orbscan II. Of 52 subjects, 26 were KC subjects and 26 were age- and sex-matched control subjects. Results: Corneal thickness, in KC patients, was significantly reduced in all areas compared with corneal thickness among controls with both the Visante optical coherence tomography and Orbscan II. Conclusion: The results of the present study have provided clinical evidence that KC is a disease affecting a wider area of the cornea. Although the KC cornea shows the greatest change in thickness in the ectatic region, this attenuation declines toward the periphery. The presence of peripheral thinning indicated that KC may be a “pancorneal” pathology and not limited to the ectatic portion.
Designing inhibitors of anthrax toxin

Introduction: Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded ‘for the development of multiscale models for complex chemical systems’ once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial-and-error approach to a minimum. The intentional dissemination of Bacillus anthracis spores in 2001 via the so-called anthrax letters has led to increased efforts, politically and scientifically, to develop medical countermeasures that will protect people from the threat of anthrax bioterrorism. Areas covered: This article provides an overview of the recent rational drug design approaches for discovering inhibitors of anthrax toxin. The review also directs the readers to the vast literature on the recognized advances and future possibilities in the field. Expert opinion: Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (protective antigen-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, the situation, in our view, is still insecure. Further, the FDA's animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Better identification and validation of anthrax toxin therapeutic targets at the molecular level as well as elucidation of the parameters determining the corresponding therapeutic windows are still necessary for more effective therapeutic options.
Denosumab Rapidly Increases Cortical Bone in Key Locations of the Femur: A 3D Bone Mapping Study in Women With Osteoporosis

Women with osteoporosis treated for 36 months with twice‐yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60 mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One‐third of the increase came from increasing cortical density, and two‐thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab‐treated women at increased risk of fracture. © 2014 American Society for Bone and Mineral Research.
New Insights into the Properties of Pubescent Surfaces: Peach Fruit as a Model1[OA]

The surface of peach (Prunus persica ‘Calrico’) is covered by a dense indumentum, which may serve various protective purposes. With the aim of relating structure to function, the chemical composition, morphology, and hydrophobicity of the peach skin was assessed as a model for a pubescent plant surface. Distinct physicochemical features were observed for trichomes versus isolated cuticles. Peach cuticles were composed of 53% cutan, 27% waxes, 23% cutin, and 1% hydroxycinnamic acid derivatives (mainly ferulic and p-coumaric acids). Trichomes were covered by a thin cuticular layer containing 15% waxes and 19% cutin and were filled by polysaccharide material (63%) containing hydroxycinnamic acid derivatives and flavonoids. The surface free energy, polarity, and work of adhesion of intact and shaved peach surfaces were calculated from contact angle measurements of water, glycerol, and diiodomethane. The removal of the trichomes from the surface increased polarity from 3.8% (intact surface) to 23.6% and decreased the total surface free energy chiefly due to a decrease on its nonpolar component. The extraction of waxes and the removal of trichomes led to higher fruit dehydration rates. However, trichomes were found to have a higher water sorption capacity as compared with isolated cuticles. The results show that the peach surface is composed of two different materials that establish a polarity gradient: the trichome network, which has a higher surface free energy and a higher dispersive component, and the cuticle underneath, which has a lower surface free energy and higher surface polarity. The significance of the data concerning water-plant surface interactions is discussed within a physiological context.
Viral Blip Dynamics during Highly Active Antiretroviral Therapy

ABSTRACT Although intermittent episodes of low-level viremia are often observed in well-suppressed highly active antiretroviral therapy (HAART)-treated patients, the timing and amplitude of viral blips have never been examined in detail. We analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50 copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years (range, 5 months to 5.3 years). The mean (± the standard deviation) blip frequency was 0.09 ± 0.11/sample, with about one-third of patients showing no viral blips. The mean viral blip amplitude was 158 ± 132 human immunodeficiency virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude distributions suggest that two blips less than 22 days apart have a significant chance of being part of the same episode of viremia. The data are consistent with a hypothetical model in which each episode of viremia consists of a phase of VL rise, followed by two-phase exponential decay. Thus, the term “viral blip” may be a misnomer, since viral replication appears to be occurring over an extended period. Neither the frequency nor the amplitude of viral blips increases with longer periods of observation, but the frequency is inversely correlated with the CD4+-T-cell count at the start of therapy, suggesting that host-specific factors but not treatment fatigue are determinants of blip frequency.