Miracle-dz/UniFAR-FTUs huggingface dataset:
Noninvasive positive pressure ventilation in status asthmaticus.

OBJECTIVE In asthmatic patients with acute respiratory failure (ARF), placing an endotracheal tube is associated with a high rate of complications and results in increased airway resistance. In acute asthma, mask-continuous positive airway pressure (CPAP) decreases airway resistance and the work of breathing (WOB), but does not improve gas exchange. In COPD with ARF, adding intermittent positive pressure ventilation to mask-CPAP results in an additional improvement in WOB and is highly effective in correcting gas exchange abnormalities. In our medical ICU, noninvasive positive pressure ventilation (NPPV) is used as first-line interventional therapy in eligible patients with hypercapnic ARF. We report our experience with NPPV in 17 episodes of asthma and ARF over a 3-year period. METHODS A face mask was secured with head straps, avoiding a tight fit, and connected to a ventilator (PB-7200). Initial ventilatory settings included CPAP at 4 +/- 2 cm H2O to offset intrinsic positive end-expiratory pressure and pressure support ventilation (PSV) at 14 +/- 5 cm H2O aiming at a respiratory rate less than 25 breaths/min and an exhaled tidal volume of 7 mL/kg or more. PSV was then adjusted following arterial blood gas results. RESULTS Mean age was 35.4 +/- 11.3 years; 10 patients were female. The mean (+/- SE) for different physiologic values are reported at initiation, less than 2 h, 2 to 6 h, and 12 to 24 h into NPPV. pH was 7.25 +/- 0.01, 7.32 +/- 0.02 (p = 0.0012), 7.36 +/- 0.02 (p < 0.0001), and 7.38 +/- 0.02; PaCO2 was 65 +/- 2, 52 +/- 3(p = 0.002), 45 +/- 3(p < 0.0001), and 45 +/- 4; PaO2 fraction of inspired oxygen was 315 +/- 41, 403 +/- 47, 367 +/- 47, and 472 +/- 67 (p = 0.06); and respiratory rate was: 29.1 +/- 1, 22 +/- 1 (p < 0.0001), 20 +/- 1, and 17 +/- 1. NPPV was well tolerated, and only two patients required sedation. Initial delivered minute ventilation was 16 +/- 4 L/min. The mean (+/- SD) peak inspiratory pressure to ventilate in the NPPV-treated patients was 18 +/- 5 cm H2O and always less than 25 cm H2O. There was no complication or problem with expectorating of secretions. Oral intake (liquid diet) was preserved. Two patients required intubation (35 min and 89 h into NPPV) for worsening PaCO2. Duration of NPPV was 16 +/- 21 h. All patients survived. Length of hospital stay was 5 +/- 4 days. CONCLUSIONS In asthmatic patients with ARF, NPPV via a face mask appears highly effective in correcting gas exchange abnormalities using a low inspiratory pressure (< 25 cm H2O). A randomized study is in progress to assess fully the role of NPPV in status asthmaticus.
An anti-NH 2-terminal antibody localizes NBCn 1 to heart endothelia and skeletal and vascular smooth muscle cells

Damkier, Helle Hasager, Søren Nielsen, and Jeppe Praetorius. An anti-NH2-terminal antibody localizes NBCn1 to heart endothelia and skeletal and vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 290: H172–H180, 2006. First published August 26, 2005; doi:10.1152/ajpheart.00713. 2005. —The electroneutral sodium bicarbonate cotransporter NBCn1 or NBC3 was originally cloned from rat aorta and from human skeletal muscle. NBCn1 (or NBC3) has been localized to the basolateral membrane of various epithelia, but thus far it has been impossible to detect the protein in these tissues by using anti-COOH-terminal antibodies. Hence an antibody was developed against the NH2-terminus of NBCn1 and was validated by peptide recognition and immunoblotting on positive control tissues and by binding of an 180-kDa protein in the rat kidney, cerebrum, cerebellum, and duodenum. In addition, an 180-kDa immunoreactive band appeared using samples from the aorta, heart ventricles and atria, mesenteric arteries, lung, spleen, liver, pancreas, and epididymis. Immunohistochemical analysis confirmed the previously described labeling in the kidney, duodenum, and the choroid plexus. The anti-NH2-terminal antibody localized NBCn1 to the plasma membrane domains of endothelia and smooth muscle cells in small mesenteric and renal arteries, as well as the capillaries of the heart ventricles, spleen, and salivary glands. NBCn1 was also detected in neuromuscular junctions and vasculature in skeletal muscle. Analysis of variable NBCn1 splicing by RT-PCR revealed that an NH2terminal sequence, the cassette III, seems absent from cardiovascular NBCn1 and that both cassettes I and III are variable in most epithelia, whereas cassette II is absent from epithelial NBCn1. Thus the development of the NH2-terminal antibody allowed the localization of NBCn1 protein to major cardiovascular tissues where NBCn1 mRNA was previously detected. The NBCn1 is a likely candidate for mediating the reported electroneutral Na -HCO3 cotransport in vascular smooth muscle.
Measuring Cerebral Activation From fNIRS Signals: An Approach Based on Compressive Sensing and Taylor–Fourier Model

Functional near-infrared spectroscopy (fNIRS) is a noninvasive and portable neuroimaging technique that uses NIR light to monitor cerebral activity by the so-called haemodynamic responses (HRs). The measurement is challenging because of the presence of severe physiological noise, such as respiratory and vasomotor waves. In this paper, a novel technique for fNIRS signal denoising and HR estimation is described. The method relies on a joint application of compressed sensing theory principles and Taylor-Fourier modeling of nonstationary spectral components. It operates in the frequency domain and models physiological noise as a linear combination of sinusoidal tones, characterized in terms of frequency, amplitude, and initial phase. Algorithm performance is assessed over both synthetic and experimental data sets, and compared with that of two reference techniques from fNIRS literature.
Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro

Chondrocyte toxicity and necrosis were seen with electron microscopy after incubation of human adult cartilage biopsy specimens in ciprofloxacin or ofloxacin. In vitro exposure of chondrocytes to fluoroquinolones did not affect apoptosis as determined by flow cytometry. While the immediate clinical significance of this finding remains unclear, the possibility of long-term cartilage damage after fluoroquinolone treatment cannot be excluded.
A randomized sequential trial of creatine in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double‐blind, placebo‐controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable‐laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo‐controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS. Ann Neurol 2003;53:437–445
Evaluation of the components of insulin‐like growth factor (IGF)‐IGF binding protein (IGFBP) system in adolescents with type 1 diabetes and persistent microalbuminuria: relationship with increased urinary excretion of IGFBP‐3 18 kD N‐terminal fragment

IGFs and their binding proteins (IGFBPs) have an important role in controlling glucose homeostasis and there is evidence to support their involvement in complications related to type I diabetes. The aim of this study was to evaluate the components of the IGF‐IGFBP system in adolescents with type 1 diabetes that had developed persistent microalbuminuria (MA).
Antisense oligonucleotides specific for regulatory factor RFX‐1 inhibit inducible but not constitutive expression of all major histocompatibility complex class II genes

The regulation of major histocompatibility complex (MHC) class II genes expression, which can be constitutive, inducible or both, is a crucial aspect of the control of an immune response. It involves binding of various regulatory factors to cis‐acting sequences of MHC class II promoters. Antisense oligonucleotides specific for RFX‐1, a regulatory factor binding to the functionally essential X box motive of MHC class II promoters, were designed to study the role of RFX‐1 in the various modes of MHC class II regulation and explore the possibility of experimentally modulating the level of expression of MHC class II genes by transcriptional intervention. RFX‐1 antisense oligonucleotides were first tested in cell‐free translation, selected for an inhibitory effect on RFX‐1 in vitro translation and then assayed in cell cultures for an effect on human histocompatibility leukocyte antigen (HLA) class II expression. We show that an RFX‐1 specific antisense oligonucleotide drastically inhibits induction of HLA‐DR, ‐DQ and ‐DP molecules by interferon γ in monocytic cells. Unexpectedly, the same agent has no effect on the constitutive expression of the same genes either in these cells or in B lymphocytes, indicating an uncoupling of the constitutive and inducible modes of class II regulation. This transient and reversible experimental modulation of MHC class II expression in live cells by transcriptional intervention provides a new tool to study the function of class II molecules in various biological models.
Audit fees and audit adjustments: evidence from Welsh local authorities

This paper exploits the availability of pre-audit financial statements to investigate the scale and incidence of audit adjustments and their impact on audit fees in Welsh local authorities. Adjustments to the politically-sensitive general fund, which represent a significant proportion of all adjustments, are associated with increased audit fees. The authors also found that audit adjustments on average result in more conservative reporting of the surplus/deficit and the balance on the general fund, with the number and value of downward adjustments exceeding those of upward movements.
Vulvar pain. Psychological profiles and treatment responses.

OBJECTIVE To compare the psychological and quality of life profiles of women with different subsets of vulvodynia and identify differential response patterns to a combined gynecologic-dermatologic treatment program. STUDY DESIGN Fifty-three women with vulvar dermatoses, dysesthetic vulvodynia and vulvar vestibulitis were recruited from a combined dermatologic and gynecologic vulvar clinic and completed instruments related to quality of life (QoL) and psychologic symptomatology. A repeated measurement design was employed. However, only 33 women could be assessed at the second point of measurement. RESULTS Women with different subsets of vulvodynia showed (1) distinct quality of life and psychological profiles, and (2) different response patterns to treatment. There were significant differences on most QoL scales, with patients with dysesthetic vulvodynia and with vulvar dermatoses showing greater impairment than patients with vestibulitis. However, patients with vestibulitis displayed a highly specific pattern of psychologic symptomatology. Patients with vulvar dermatoses had an improvement in problems related to intimacy than patients with vulvar pain syndromes. CONCLUSION Treatment intervention studies seem to be indispensable in order to gain a better understanding of the complex interplay between different subsets of vulvodynia and psychological symptoms concurrently with differential treatment reactions.
Tbx5 is required for forelimb bud formation and continued outgrowth

Tbx5 is a T-box transcription factor expressed exclusively in the developing forelimb but not in the developing hindlimb of vertebrates. Tbx5 is first detected in the prospective forelimb mesenchyme prior to overt limb bud outgrowth and its expression is maintained throughout later limb development stages. Direct evidence for a role of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt-Oram Syndrome (HOS), a dominant disorder characterised predominantly by upper(fore) limb defects and heart abnormalities. Misexpression studies in the chick have demonstrated a role for this gene in limb-type specification. Using a conditional knockout strategy in the mouse to delete Tbx5 gene function in the developing forelimb, we demonstrate that this gene is also required at early limb bud stages for forelimb bud development. In addition, by misexpressing dominant-negative and dominant-activated forms of Tbx5 in the chick wing we provide evidence that this gene is also required at later stages of limb bud development for continued limb outgrowth. Our results provide a context to understand the defects observed in HOS caused by haploinsufficiency of TBX5 in human. Moreover, our results also demonstrate that limb bud outgrowth and specification of limb identity are linked by a requirement for Tbx5.
Spontaneous intra-cerebral hemorrhage: A retrospective study of risk factors and outcome in a Turkish population

Background and Purpose: Stroke, which remains the third leading cause of death after heart disease and cancer in developed countries, is a disorder causing permanent neurologic disability. Even though, hemorrhagic strokes are seen less than the ischemic type, they are more fatal. We studied the risk factors for spontaneous intra-cerebral hemorrhage (ICH) to direct the proper preventive treatment modalities and the effects of these factors on mortality as well as applied therapeutic strategies on survival. Materials and Methods: The archive records of 106 patients (60 male, 46 female) who were diagnosed with spontaneous ICH in Baskent University Hospital, Ankara, between January 2003 and September 2008, were assessed retrospectively. Results: The mean age was found as 62.5. The most frequent risk factor was hypertension (73.5%); 69.2% of these hypertensive patients had uncontrolled blood pressure levels. The mortality rate was detected as 34.9% and patients were found to die approximately within 9 days after ICH. Older age, increased hemorrhage volume, ventricular extension of hemorrhage, and the presence of midline shift were found to significantly correlate with increased mortality (P < 0.05). Patients who underwent surgical therapy showed a longer survival rate (P = 0.016); however, no association was found between medical and surgical therapy in terms of mortality (P = 0.555). Conclusion: The results of this study suggest that effective control of blood pressure is important in the prevention of spontaneous ICH; clinical and radiological findings with treatment modalities influencing mortality should be carefully managed.
Characterization of cry Genes in a Mexican Bacillus thuringiensis Strain Collection

ABSTRACT Mexico is located in a transition zone between the Nearctic and Neotropical biogeographical regions and contains a rich and unique biodiversity. A total of 496 Bacillus thuringiensis strains were isolated from 503 soil samples collected from the five macroregions of the country. The characterization of the strain collection provided useful information on the ecological patterns of distribution of B. thuringiensis and opportunities for the selection of strains to develop novel bioinsecticidal products. The analysis of the strains was based on multiplex PCR with novel general and specific primers that could detect the cry1,cry3, cry5, cry7, cry8,cry9, cry11, cry12,cry13, cry14, cry21, andcyt genes. The proteins belonging to the Cry1 and Cry9 groups are toxic for lepidopteran insects. The Cry3, Cry7, and Cry8 proteins are active against coleopteran insects. The Cry5, Cry12, Cry13, and Cry14 proteins are nematocidal. The Cry11, Cry21, and Cyt proteins are toxic for dipteran insects. Six pairs of general primers are used in this method. Strains for which unique PCR product profiles were obtained with the general primers were further characterized by additional PCRs with specific primers. Strains containingcry1 genes were the most abundant in our collection (49.5%). Thirty-three different cry1-type profiles were identified. B. thuringiensis strains harboringcry3 genes represented 21.5% of the strains, and 7.9% of the strains contained cry11 and cyt genes.cry7, cry8, and cry9 genes were found in 0.6, 2.4, and 2.6% of the strains, respectively. No strains carrying cry5, cry12, cry13,cry14, or cry21 genes were found. Finally, 14% of the strains did not give any PCR product and did not react with any polyclonal antisera. Our results indicate the presence of strains that may harbor potentially novel Cry proteins as well as strains with combinations of less frequently observed cry genes.
Pharmacology of transient receptor potential melastatin channels in the vasculature

Mammalian transient receptor potential melastatin (TRPM) non‐selective cation channels, the largest TRP subfamily, are widely expressed in excitable and non‐excitable cells where they perform diverse functions ranging from detection of cold, taste, osmolarity, redox state and pH to control of Mg2+ homeostasis and cell proliferation or death. Recently, TRPM gene expression has been identified in vascular smooth muscles with dominance of the TRPM8 channel. There has been in parallel considerable progress in decoding the functional roles of several TRPMs in the vasculature. This research on native cells is aided by the knowledge of the activation mechanisms and pharmacological properties of heterologously expressed TRPM subtypes. This paper summarizes the present state of knowledge of vascular TRPM channels and outlines several anticipated directions of future research in this area.
Mathematical Modeling of Vesicle Drug Delivery Systems 2

Vesicles have been studied for several years in their ability to deliver drugs. Mathematical models have much potential in reducing time and resources required to engineer optimal vesicles, and this review article summarizes these models that aid in understanding the ability of targeted vesicles to bind and internalize into cancer cells, diffuse into tumors, and distribute in the body. With regard to binding and internalization, radiolabeling and surface plasmon resonance experiments can be performed to determine optimal vesicle size and the number and type of ligands conjugated. Binding and internalization properties are also inputs into a mathematical model of vesicle diffusion into tumor spheroids, which highlights the importance of the vesicle diffusion coefficient and the binding affinity of the targeting ligand. Biodistribution of vesicles in the body, along with their half-life, can be predicted with compartmental models for pharmacokinetics that include the effect of targeting ligands, and these predictions can be used in conjunction with in vivo models to aid in the design of drug carriers. Mathematical models can prove to be very useful in drug carrier design, and our hope is that this review will encourage more investigators to combine modeling with quantitative experimentation in the field of vesicle-based drug delivery.
Achieving and Sustaining Quality in Healthcare

Summary • SSM Health Care (SSMHC), the first healthcare recipient of the Malcolm Baldrige National Quality Award, has been cited by both Baldrige and the Joint Commission on Accreditation of Healthcare Organizations as having a culture of continuous quality improvement (CQI). SSM Health Care began to implement CQI systemwide in 1990. CQI provided the foundation for other strategies that served to further weave quality improvement into the fabric of the organization's culture. It gave SSMHC's people the tools and techniques to make improvements, created an environment of teamwork, and introduced the concept of improving processes. Using the Baldrige Criteria for Performance Excellence as a business model helped SSMHC to see how various organizational functions should link and to discover gaps in the linkage within its own organization. Baldrige feedback reports identified opportunities that could then be prioritized and the resulting improvements implemented. Overall, the Baldrige model gave a focused approach to what had been scattered improvement efforts. SSM Health Care considers the Baldrige model the best way for an organization to get better faster.
Multiple N‐acetyl neuraminic acid synthetase (neuB) genes in Campylobacter jejuni: identification and characterization of the gene involved in sialylation of lipo‐oligosaccharide

N‐acetyl neuraminic acid (NANA) is a common constituent of Campylobacter jejuni lipo‐oligosaccharide (LOS). Such structures often mimic human gangliosides and are thought to be involved in the triggering of Guillain–Barré syndrome (GBS) and Miller–Fisher syndrome (MFS) following C. jejuni infection. Analysis of the C. jejuni NCTC 11168 genome sequence identified three putative NANA synthetase genes termed neuB1, neuB2 and neuB3. The NANA synthetase activity of all three C. jejuni neuB gene products was confirmed by complementation experiments in an Escherichia coli neuB‐deficient strain. Isogenic mutants were created in all three neuB genes, and for one such mutant (neuB1) LOS was shown to have increased mobility. C. jejuni NCTC 11168 wild‐type LOS bound cholera toxin, indicating the presence of NANA in a LOS structure mimicking the ganglioside GM1. This property was lost in the neuB1 mutant. Gas chromatography–mass spectrometry and fast atom bombardment–mass spectrometry analysis of LOS from wild‐type and the neuB1 mutant strain demonstrated the lack of NANA in the latter. Expression of the neuB1 gene in E. coli confirmed that NeuB1 was capable of in vitro NANA biosynthesis through condensation of N‐acetyl‐d‐mannosamine and phosphoenolpyruvate. Southern analysis demonstrated that the neuB1 gene was confined to strains of C. jejuni with LOS containing a single NANA residue. Mutagenesis of neuB2 and neuB3 did not affect LOS, but neuB3 mutants were aflagellate and non‐motile. No phenotype was evident for neuB2 mutants in strain NCTC 11168, but for strain G1 the flagellin protein from the neuB2 mutant showed an apparent reduction in molecular size relative to the wild type. Thus, the neuB genes of C. jejuni appear to be involved in the biosynthesis of at least two distinct surface structures: LOS and flagella.