Miracle-dz/UniFAR-FTUs huggingface dataset:
25% "error rate" in ear temperature sensing device.

To the Editor. — We read with interest the recent article by Kenney et al1 regarding the acceptability of the FIRST temp (Intelligent Medical Systems, Inc., Carlsbad, CA) tympanic membrane infrared temperature sensing device as a clinical tool for pediatricians.1 The authors conclude that the instrument provides body temperature measurements consistent with traditionally used methods (glass-mercury thermometer). We take exception with the analysis used to reach such a conclusion. The authors present their data as mean differences between FIRST temp and conventional methods with 95% confidence intervals around the mean.
Influence of acetazolamide on cerebral blood flow.

Carbonic anhydrase inhibitors have been used in clinical medicine as diuretics, 1-3 as anticonvulsants, 4,5 to reduce intraocular tension, 6,7 to lower intracranial pressure, 8,9 and in the treatment of respiratory insufficiency. 10,11 In the course of investigation of the effects of acetazolamide in hepatic encephalopathy, Posner and Plum 12 observed without comment a considerable increase in rate of cerebral blood flow after intravenous administration of 1 to 2 gm. of acetazolamide. Such a cerebral circulatory change had previously been considered to account for the brief elevation of cerebrospinal fluid pressure after intravenous acetazolamide. 9,13 In view of these findings, we felt that the usefulness of carbonic anhydrase inhibitors might be extended to the management of patients with intermittent cerebral vascular insufficiency. In this preliminary report, observations of the quantitative cerebral hemodynamic effects of intravenous acetazolamide are presented. In several subjects, the effects of inhalation of 5% CO 2 were
Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.

Two variant amino acid sequences, which differ in a single amino acid residue, have been reported for the alpha 1‐subunit of the rat brain GABAA receptor. We separately co‐expressed these two variants in Xenopus oocytes, in combination with beta 2 and gamma 2. This experiment showed that substitution of alpha 1‐Phe64 by Leu strongly decreases the apparent affinity for GABA dependent channel gating from 6 microM to 1260 microM. Starting from this observation, we used in vitro mutagenesis to obtain information relevant for the localization of the agonist/antagonist binding site in the GABAA receptor. Homologous mutation in alpha 5 had similar consequences for alpha 5 beta 2 gamma 2. Homologous mutation in beta 2 and gamma 2 resulted in intermediate and small shifts in EC50, respectively. The apparent affinities of the competitive antagonists bicuculline methiodide and SR95531, the latter sharing close structural similarity with the agonist GABA, were decreased 60‐ to 200‐fold by these mutations in alpha‐subunits. Interestingly, these affinities remained nearly unaffected upon introduction of the homologous mutations in beta 2 and gamma 2, or upon mutation of the neighbouring amino acid in alpha 1, Phe65 to Leu. These results suggest close functional and structural association of alpha‐subunits with the agonist/antagonist binding site, and involvement of N‐terminal portions of the extracellular domains of all subunits in the gating of the channel.
Multiple Nucleosome Positioning Sites Regulate the CTCF-Mediated Insulator Function of the H19 Imprinting Control Region†

ABSTRACT The 5′ region of the H19 gene harbors a methylation-sensitive chromatin insulator within an imprinting control region (ICR). Insertional mutagenesis in combination with episomal assays identified nucleosome positioning sequences (NPSs) that set the stage for the remarkably precise distribution of the four target sites for the chromatin insulator protein CTCF to nucleosome linker sequences in the H19 ICR. Changing positions of the NPSs resulted in loss of both CTCF target site occupancy and insulator function, suggesting that the NPSs optimize the fidelity of the insulator function. We propose that the NPSs ensure the fidelity of the repressed status of the maternal Igf2 allele during development by constitutively maintaining availability of the CTCF target sites.
Keratoconus Progression in Patients With Allergy and Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test

Purpose: To assess keratoconus (KC) progression in patients with allergies who also tested positive to surface matrix metalloproteinase 9 (MMP-9) point-of-care test. Methods: Prospective comparative study including 100 stage I–II keratoconic patients, mean age 16.7±4.6 years. All patients underwent an anamnestic questionnaire for concomitant allergic diseases and were screened with the MMP-9 point-of-care test. Patients were divided into two groups: patients KC with allergies (KC AL) and patients KC without allergies (KC NAL). Severity of allergy was established by papillary subtarsal response grade and KC progression assessed by Scheimpflug corneal tomography, corrected distance visual acuity (CDVA) measurement in a 12-month follow-up. Results: The KC AL group included 52 patients and the KC NAL group 48. In the KC AL group, 42/52 of patients (81%) were positive to MMP-9 point-of-care test versus two positive patients in the KC NAL group (4%). The KC AL group data showed a statistically significant decrease of average CDVA, from 0.155±0.11 to 0.301±0.2 logarithm of the minimum angle of resolution (P<0.005) at 12 months; Kmax value increased significantly, from 50.2 D±2.7 to 55.2 D±1.9 on average. The KC NAL group revealed a slight KC progression without statistically significant changes. Pearson correlation test showed a high correlation between Kmax worsening and severity of PSR in the KC AL group. Conclusions: The study demonstrated a statistically significant progression of KC in patients with concomitant allergies, positive to MMP-9 point-of-care test versus negative. A high correlation between severity of allergy and KC progression was documented.
Cross‐regulation of competence pheromone production and export in the early control of transformation in Streptococcus pneumoniae

Two operons, comAB and comCDE, play a key role in the co‐ordination of spontaneous competence development in cultures of Streptococcus pneumoniae. ComAB is required for export of the comC‐encoded competence‐stimulating peptide (CSP). Upon CSP binding, the histidine kinase ComD activates ComE, its cognate response regulator, required for autoinduction of comCDE and for induction of the late competence genes. To understand better the early control of competence development, mutants upregulating comCDE (ComCDEUP) were isolated using a comC–lacZ transcriptional fusion. Mutants were generated by polymerase chain reaction mutagenesis of the comCDE region and by in vitro transposon mutagenesis of the chromosome. Both types of ComCDEUP mutants exhibited similar phenotypes. They differed from wild type in displaying trypsin‐resistant transformation, competence under acid growth conditions and expression of comCDE under microaerobiosis; increased production of CSP in the mutants could account for the various phenotypes. The ComCDEUP transposon mutations included four independent insertions in the ciaR gene, which encodes the response regulator of a two‐component system previously found to affect competence, and two immediately upstream of the comAB operon. The latter two resulted in comAB overexpression, indicating that CSP export is rate limiting. Among comDE point mutations, a single amino acid change in ComD (T233I) conferred constitutive, CSP‐independent competence and resulted in comAB overexpression, providing support for the hypothesis that ComE regulates comAB; a ComE mutant (R120S) exhibited altered kinetics of competence shut‐off. Collectively, these data indicate that pheromone autoinduction, cross‐regulation of the comAB and comCDE operons and, possibly, competence shut‐off contribute to the early control of competence development in S. pneumoniae. They argue for a metabolic control of competence, mediated directly or indirectly by CiaR, and they suggest that both comAB and comCDE are potential targets for regulation.
CB1 RECEPTOR ACTIVATION IN THE BASOLATERAL AMYGDALA PRODUCES ANTINOCICEPTION IN ANIMAL MODELS OF ACUTE AND TONIC NOCICEPTION

1 Recent studies have suggested that the basolateral nucleus of the amygdala (BLA) participates in the processing of pain information, especially noxious somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the BLA than in other nuclei of the amygdala. Thus, the aim of the present study was to examine whether CB1 receptors in the BLA may be involved in modulating acute and/or tonic nociceptive processing. 2 Adult rats were exposed to intra‐BLA microinjection of the cannabinoid receptor agonist (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl) pyrrolo [1,2,3,‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐naphthalenylmethanone mesylate [WIN 55,212‐2 (1, 2.5, 5 or 10 µg/side)] and subjected to the tail flick and formalin tests. 3 The rats demonstrated a dose‐dependent increase in latency to withdraw from a thermal noxious stimulus in the tail flick test and a decrease in formalin‐induced pain behaviours. The antinociceptive effects of the CB1 receptor agonist WIN 55,212‐2 (10 µg/side) in both tests were attenuated in the presence of the selective CB1 receptor antagonist, N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐ carboxamide (AM251; 0.55 ng/side). Administration of the CB1 receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the nociceptive thresholds in either test. Bilateral microinjection of the selective CB2 receptor antagonist N‐[(1S)‐endo‐1,3,3‐trimethyl bicyclo [2.2. 1] heptan‐2‐yl]‐5‐(4‐chloro‐3‐methylphenyl)‐1‐(4‐methylbenzyl)‐pyrazole‐3‐carboxamide (SR144528; 1 µg/side) had no effect on the antinociception produced by WIN 55,212‐2, suggesting that the antinociceptive actions of WIN 55,212‐2 are mediated by CB1 receptors. 4 The findings suggest the existence of a CB1‐mediated inhibitory system in the BLA that, when activated, can diminish responsivity to acute and tonic noxious stimuli, but that normally has no tonic effect on the response threshold of these stimuli.
Symbiodinium spp. in colonies of eastern Pacific Pocillopora spp. are highly stable despite the prevalence of low-abundance background populations

A shift in the dominant Symbiodinium species within a coral colony may allow rapid ac - climatization to environmental stress, provided that the new symbiont is better suited to prevailing conditions. In this study, the Symbiodinium diver- sity in Pocillopora corals was examined following a cold-water bleaching event in the Gulf of Cali- fornia. Individual colonies were differentially im - pacted by this event based upon their association with either the Symbiodinium ITS-2 type C1b-c (sensitive) or ITS-2 type D1 (tolerant). Real-time PCR indicated a high prevalence of an alternate and compatible Symbiodinium sp. (i.e. C1b-c or D1) residing at low-abundance background levels within many colonies both during and after a 1 yr recovery interval (46 to 52%). However, despite the potential for 'switching,' the dominant resident symbiont remained at high abundance during the recovery, with only 2 of 67 colonies (3%) under - going a change to the other Symbiodinium type. Pocillopora residing in the Gulf of California there- fore maintain long-term associations dominated by a specific Symbiodinium sp. , where potential com- petition by a second symbiont type is suppressed despite the temporary change in environmental conditions that would favor a shift in symbiosis toward a more stress-tolerant species.
Caregiving demands during advanced cancer: The spouse's needs

This descriptive study explored the demands made by spouse caregivers of terminally ill, adult cancer patients. A one-time, semistructured, at-home interview with 65 spouses, was conducted by the investigator. Content analyses of spouse caregiver interviews revealed nine major categories of caregiving demands. The demand reported most frequently (by 69% of the sample) was managing the physical care, treatment regimen, and imposed changes. The two next most frequently reported caregiving demand categories (both reported by 39% of the sample) were managing the household and finances and standing by. The other six categories included alterations in spouse caregiver's well being and patterns of living, constant vigilance, unmet expectations from health care system, cancer itself, anticipating the future, and alterations in relationship with ill spouse. This research provides new information as to the demands experienced by family members who are caring for a spouse with advanced cancer in the home.
Differential expression of IQGAP1/2 in Hepatocellular carcinoma and its relationship with clinical outcomes.

PURPOSE To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. METHODS IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. RESULTS IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). CONCLUSION Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.
Investigation of the characteristics of nucleobases using broadband Terahertz spectroscopy

To better understand the mechanics of deoxyribonucleic acids (DNA), the collective vibrational modes of the individual nucleobases are investigated through Terahertz (THz) spectroscopy using a Fourier Transform spectrometer (FTS). It has been shown, using terahertz time-domain spectroscopy (THz-TDS) that the nucleobases and nucleosides have distinctive spectral features between 0.6 to 4 THz [1]. Presented here is the full spectral content of the nucleobases from 0.6 THz to 18 THz by using a safe and novel technique.
An Excellent Lightness

In a report in this issue, Rossi et al. (p. 1104) describe neurons in the visual cortex that likely mediate part of the phenomenon of “brightness induction. ” In his Perspective, Albright explains brightness induction, exploited by artists to increase the perceived range of light in a painting. The new work takes us closer toward understanding the basis of visual perception.
Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties.

2-Aminobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid (9) was designed as a conformationally constrained analog of glutamic acid. For 9, the key torsion angles (tau 1 and tau 2) which determine the relative positions of the alpha-amino acid and distal carboxyl functionalities are constrained where tau 1 = 166.9 degrees or 202 degrees and tau 2 = 156 degrees, respectively. We hypothesized that 9 would closely approximate the proposed bioactive conformation of glutamate when acting at group 2 metabotropic glutamate receptors (mGluRs). The racemic target molecule (+/-)-9, its C2-diastereomer (+/-)-16, and its enantiomers (+)-9 (LY354740) and (-)-9 (LY366563) were prepared by an efficient, stereocontrolled, and high-yielding synthesis from 2-cyclopentenone. Our hypothesis that 9 could interact with high affinity and specificity at group 2 mGluRs has been supported by the observation that (+/-)-9 (EC50 = 0.086 +/- 0.025 microM) and its enantiomer (+)-9 (EC50 = 0.055 +/- 0.017 microM) are highly potent agonists for group 2 mGluRs in the rat cerebral cortical slice preparation (suppression of forskolin-stimulated cAMP formation) possessing no activity at other glutamate receptor sites (iGluR or group 1 mGluR) at concentrations up to 100 microM. Importantly, the mGluR agonist effects of (+)-9 are evident following oral administration in mice in both the elevated plus maze model of anxiety (ED50 = 0.5 mg/kg) and in the ACPD-induced limbic seizure model (ED50 = 45.6 mg/kg). Thus, (+)-9 is the first orally active group 2 mGluR agonist described thus far and is an important tool for studying the effects of compounds of this class in humans.
Central nervous system effects of acute organophosphate poisoning in a two-year follow-up.

OBJECTIVES Patients hospitalized for acute organophosphate poisoning in León, Nicaragua, were followed for effects on the central nervous system (CNS) over a 2-year period. METHODS Immediate verbal memory (Rey verbal learning), visuomotor performance (digit symbol), and neuropsychiatric symptoms (Q-16) were assessed for 53 poisoned persons at the time of hospital discharge, 7 weeks postpoisoning, and 2 years postpoisoning, and, at the same time intervals, for 28 persons who had never been poisoned. The poisonings were classified as moderate occupational (31), severe occupational (15), and severe through the oral route (7), representing low, medium, and high exposure, respectively. Longitudinal confounder-adjusted between-category comparisons and longitudinal analyses of variance and covariance were used to assess the effects of the exposure. RESULTS Immediate verbal learning showed deficits in the high-exposure group, in particular at the time of discharge, but the estimate of the difference when compared with the values of the unexposed was imprecise. Visuomotor performance showed a deficit at 7 weeks in the medium-exposure group, but it had improved after 2 years relative to that of the unexposed, for whom improvement had occurred at 7 weeks and persisted during the 2 years of follow-up, possibly a test-retest effect. Neuropsychiatric symptoms were in excess 2 years after the hospital discharge in the low- and medium-exposure groups and all the groups combined. All the results were imprecise for the small high-exposure group. CONCLUSIONS Visuomotor performance and possibly short-term verbal memory seem to be affected early after severe acute organophosphate poisoning and recover, either truly or by some compensatory mechanism. Neuropsychiatric symptoms seem to increase after a longer latency period.
Bacterial toxins can inhibit host cell autophagy through cAMP generation

Autophagy plays a significant role in innate and adaptive immune responses to microbial infection. Some pathogenic bacteria have developed strategies to evade killing by host autophagy. These include the use of ‘camouflage’ proteins to block targeting to the autophagy pathway and the use of pore-forming toxins to block autophagosome maturation. However, general inhibition of host autophagy by bacterial pathogens has not been observed to date. Here we demonstrate that bacterial cAMP-elevating toxins from B. anthracis and V. cholera can inhibit host anti-microbial autophagy, including autophagic targeting of S. Typhimurium and latex bead phagosomes. Autophagy inhibition required the cAMP effector protein kinase A. Formation of autophagosomes in response to rapamycin and the endogenous turnover of peroxisomes was also inhibited by cAMP-elevating toxins. These findings demonstrate that cAMP-elevating toxins, representing a large group of bacterial virulence factors, can inhibit host autophagy to suppress immune responses and modulate host cell physiology.
Exploring Individual Care Plan for a Good Sleep

This paper focuses on care plans (i.e., rough schedules) in care houses and evaluates them from the viewpoint of a deep and stable sleep which contributes to provide comfortable and healthy life for aged persons. For this purpose, this paper investigates the care plans which are basically based on the current care plans but change a small part of a schedule as an aged person desires. Through the human subject experiments in the actual care house, the following implications have been revealed: (1) the proposed care plan decreases the time of the light sleep; and (2) the proposed care plan provides the deep sleep (i.e., 9 years younger sleep in our experiment).
Purification and characterization of a halotolerant intracellular protease from Bacillus subtilis strain FP‐133

A halotolerant strain FP‐133, able to grow at concentrations of 0–12.5% (w/v) NaCl, was isolated from a fish paste and identified as Bacillus subtilis . B. subtilis strain FP‐133 produced an intracellular protease which showed catalytic activity under saline conditions. The enzyme was purified to homogeneity 143‐fold with a yield of 0.9%. The purified enzyme showed an optimum activity at a concentration of 5% (w/v) NaCl. After storage in 7.5% (w/v) NaCl at 4 °C for 24 h, the enzyme kept 100% of its activity. The molecular mass of the protease was determined to be 59 kDa by gel filtration; the protein consisted of four subunits each with a molecular mass of 14 kDa. The enzyme showed aminopeptidase activity. It acted on l‐leucyl‐p ‐nitroanilide, l‐leucyl‐β‐naphthylamide, and oligopeptides containing glycine, l‐histidine, or l‐leucine. The Km and V max values for l‐leucyl‐p ‐nitroanilide were 18 µm and 2.2 mm/h mg, respectively. The enzyme was activated by Fe2+, Fe3+, and Ni2+ in synergism with Mg2+. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)