The inevitable partnership between healthcare practice and healthcare buildings.
In this paper, the author points out the tightly-woven relationship between the healthcare provider and the facilities in which the care takes place. This relationship has evolved from the earliest days of organized medicine. Further, he asserts that in these days of reform and of heightened consumer expectations, the facilities controlled by the provider are among his most important assets. Examples cited cover intensive care settings, ambulatory care, and patient-focused care concepts. The author concludes by speculating on the form that the healthcare facilities of the future might take and on some strategies that the provider might follow.


Analytical validation of an ELISA for measurement of canine pancreas-specific lipase.
The diagnosis of canine pancreatitis is challenging. Clinical presentation often includes nonspecific clinical signs, such as vomiting, anorexia, and abdominal discomfort. Increased serum lipase activity can be indicative of pancreatitis; however, it can also be increased with other conditions. An immunoassay for measurement of canine pancreas-specific lipase in canine serum that would be suitable for commercial application and provide rapid results would be beneficial. The goal of this study was to validate the Spec cPL assay, a commercially available ELISA for the quantitative measurement of canine pancreas-specific lipase. Dynamic range, dilutional linearity, precision, interfering substances, assay stability, and reproducibility were investigated for analytical validation. The method was compared with the reference assay, canine pancreatic lipase immunoreactivity (cPLI), and included evaluation of a sample population of dogs and bias. Analytical validation showed a dynamic range of 36-954 μg/L; good precision (intra- and interassay coefficient of variation <12%); absence of interference from lipid, hemoglobin, or bilirubin; 12-month kit stability; and good reproducibility. Method comparison showed a positive bias relative to the cPLI reference method; however, the bias can be accommodated by adjustment of decision limits. The upper limit of the reference interval for Spec cPL was determined to be 216 μg/L based on the upper 97.5th percentile of results from 93 clinically healthy, kennel-housed dogs. Validation data demonstrated that the Spec cPL assay provides reproducible results for canine pancreas-specific lipase. A readily available assay for measurement of this enzyme allows broader clinical utilization of this analytical tool, generating timely results to aid in the diagnosis of canine pancreatitis.


[Simultaneous determination of neopterin and biopterin in urine by high performance liquid chromatography].
A method was established for simultaneous determination of neopterin (NP) and biopterin (BP) in urine by high performance liquid chromatography-fluorescence detection. column, Hypersil BDS C18 (4.6 mm i. d. x 200 mm, 5 microm); mobile phase, methanol-water (10:90, v/v); flow rate, 0.5 mL/min; column temperature, 20 degrees C; excitation wavelength, 360 nm; emission wavelength, 440 nm. Urine samples were first precipitated with trichloroacetic acid, then centrifuged at 12 000 r/min for 15 min at 4 degrees C, and finally added with NaOH to neutralize the supernatant. Injection volume was 30 microL. The linear ranges of determination of the standards NP and BP were 0.12 - 1000 microg/L and 0.48 -1000 microg/L, with the detection limits of 0.01 microg/L and 0.1 mictog/L, the relative standard deviations (RSDs) in urine of 1.09% and 3.39%, and average recoveries of 100.7% and 100.3%, respectively. The concentrations of NP and BP, and concentration ratio of NP and BP in urines were detected and compared between controls and uremia patients. The concentration of creatinine (Cr) in urines was detected with picric acid method. The concentration ratios of NP and Cr, NP and BP in uremia group increased more significantly than that in normal group (P < 0.05). The method is simple, fast, accurate and convenient. It can be used to detect NP and BP for clinical urine samples and provide a more convenient and accurate tool for the diagnosis of patients.


New perspectives by imaging modalities for an old illness: Rheumatic mitral stenosis.
Mitral stenosis (MS) is a progressive and devastating disease and most often occurs among young women. Given its considerable prevalence in Mediterranean and Eastern European countries according to the Euro Heart Survey, new imaging modalities are warranted to improve the management of patients with this condition. A wide spectrum of abnormalities occurs involving all parts of this complex structure and causing different grades of MS and/or regurgitation as a consequence of rheumatic affection. Novel imaging modalities significantly improved the assessment of several aspects of this rheumatic destructive process including the morphological alterations of the mitral valve apparatus, left atrial (LA) function, LA appendage, right and left ventricular function, and complications, namely, atrial fibrillation and thromboembolic events. Furthermore, new imaging modalities improved the prediction of outcome of patients who underwent percutaneous balloon mitral comissurotomy and changed the paradigm of patient selection for intervention and risk stratification. The present review aimed to summarize the role of new multimodality, multiparametric imaging approaches to assess the morphological characteristics of the rheumatic MS and its associated complications, and to guide patient management.


Vaginal mass caused by a lately recognized congenital bladder diverticulum.
Congenital bladder diverticula are strongly associated with vesicoureteral reflux (VUR), and are mostly present in childhood. The most common symptom is urinary tract infection at the time of admission. The diverticulum is usually solitary and its location is near the ureteral orifice, which is probably the main cause of VUR. We report a woman who presented with a vaginal mass located on the right inferior part of the external urethral meatus. The patient had a history of recurrent urinary tract infection and right nephrectomy due to VUR nephropathy. We examined her with cystography, computerized tomography, and cystoscopy. The cystoscopic examination was very diagnostic in our patient. The patient underwent diverticulectomy, and after 6 months of follow-up, her complaints had completely disappeared.


Development of an ELISA for detection of antibody in leprosy.
An ELISA system was developed for detection of antibodies in leprosy using whole cells of bacteria as an antigen. Whole cells of M. smegmatis, M. vaccae, M. scrofulaceum, M. leprae, C. diphtheriae, and C. xerosis were compared. M. smegmatis was the most reactive against lepromatous sera with OD492 readings 1.5 times and five times higher than the others. In addition, when M. smegmatis were coated to microtiter plates with a volatile ammonium acetate/carbonate buffer and air dried, the antigen coating was found to be three times more reactive than antigen coated with nonvolatile Na borate buffer. Autoclaving M. smegmatis increased the reactivity with lepromatous sera 1.4- to 2.3-fold. M. leprae was found to be 4-10 times more reactive than autoclaved M. smegmatis. Autoclaving M. leprae did not increase reactivity. Antibody titers of some lepromatous sera had endpoint titers of greater than 1:10,000. Both antihuman IgG and antihuman IgA, IgM, and IgG combined conjugates were found to be equally effective in detecting high levels of antibody in patients with multibacillary diseases.


Diagnosing lanolin contact allergy with lanolin alcohol and Amerchol L101.
The prevalence of lanolin contact allergy in dermatitis patients varies from 1.2% to 6.9%. Different lanolin derivatives are used in patch testing. To determine which combination of lanolin derivatives is most effective in patch testing for the diagnosis of lanolin contact allergy. A retrospective analysis of patients patch tested between 2016 and 2017 was performed. Patients were eligible if they had been tested with lanolin alcohol 30% pet., Amerchol L101 50% pet., and a supplementary series containing other lanolin derivatives. Lanolin alcohol and Amerchol L101 were tested in duplicate. Of 594 patients, 28.6% (95% confidence interval [CI]: 25.1%-32.3%) had a positive patch test reaction to at least one lanolin derivative. Reactions to lanolin alcohol (14.7%, 95%CI: 11.3%-18.2%) and Amerchol L101 (15.0%, 95%CI: 11.5%-18.5%) were common in the routinely tested series. Reactions to other test preparations were significantly less frequent (P < 0.05). The addition of Amerchol L101 to lanolin alcohol significantly increased the number of positive cases (odds ratio 1.79, P < 0.001). The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for the diagnosis of lanolin contact allergy. Routinely testing with other lanolin derivatives may not be worthwhile, as it detects only a few additional patients.


Targeted transgenesis identifies Gαs as the bottleneck in β2-adrenergic receptor cell signaling and physiological function in airway smooth muscle.
G protein-coupled receptors are the most pervasive signaling superfamily in the body and act as receptors to endogenous agonists and drugs. For β-agonist-mediated bronchodilation, the receptor-G protein-effector network consists of the β2-adrenergic receptor (β2AR), Gs, and adenylyl cyclase, expressed on airway smooth muscle (ASM). Using ASM-targeted transgenesis, we previously explored which of these three early signaling elements represents a limiting factor, or bottleneck, in transmission of the signal from agonist binding to ASM relaxation. Here we overexpressed Gαs in transgenic mice and found that agonist-promoted relaxation of airways was enhanced in direct proportion to the level of Gαs expression. Contraction of ASM from acetylcholine was not affected in Gαs transgenic mice, nor was relaxation by bitter taste receptors. Furthermore, agonist-promoted (but not basal) cAMP production in ASM cells from Gαs-transgenic mice was enhanced compared with ASM from nontransgenic littermates. Agonist-promoted inhibition of platelet-derived growth factor-stimulated ASM proliferation was also enhanced in Gαs mouse ASM. The enhanced maximal β-agonist response was of similar magnitude for relaxation, cAMP production, and growth inhibition. Taken together, it appears that a limiting factor in β-agonist responsiveness in ASM is the expression level of Gαs. Gene therapy or pharmacological means of increasing Gαs (or its coupling efficiency to β2AR) thus represent an interface for development of novel therapeutic agents for improvement of β-agonist therapy.


Subjective and objective olfactory abnormalities in Crohn's disease.
The pathogenesis of Crohn's disease (CD) is still unknown, but the involvement of the olfactory system in CD appears possible. No study to date has systematically assessed the olfactory function in CD patients. We investigated the olfactory function in CD patients in active (n = 31) and inactive disease (n = 27) and in a control group of age- and sex-matched healthy subjects (n = 35). Subjective olfactory testing was applied using the Sniffin' Sticks test. For olfactory testing, olfactory event-related potentials (OERPs) were obtained with a 4-channel olfactometer using phenyl ethyl alcohol (PEA) and hydrogen sulfide (H(2)S). Carbon dioxide (CO(2)) was employed as control stimulus, and chemosomatosensory event-related potentials (CSSERPs) were registered. Results of the Sniffin' Sticks test revealed significantly different olfactory hedonic judgment with increased olfactory hedonic estimates for pleasant odorants in CD patients in active disease compared with healthy subjects. A statistical trend was found toward lower olfactory thresholds in CD patients. In objective olfactory testing, CD patients showed lower amplitudes of OERPs and CSSERPs. Additionally, OERPs showed significantly shorter N1- and P2 latencies following stimulation of the right nostril with H(2)S in CD patients in inactive disease compared with controls. Our study demonstrates specific abnormalities of olfactory perception in CD patients.


The effect of small changes in hematocrit on nitric oxide transport in arterioles.
We report the development of a mathematical model that quantifies the effects of small changes in systemic hematocrit (Hct) on the transport of nitric oxide (NO) in the microcirculation. The model consists of coupled transport equations for NO and oxygen (O2) and accounts for both shear-induced NO production by the endothelium and the effect of changing systemic Hct on the rate of NO production and the rate of NO scavenging by red blood cells. To incorporate the dependence of the plasma layer width on changes in Hct, the model couples the hemodynamics of blood in arterioles with NO and O2 transport in the plasma layer. A sensitivity analysis was conducted to determine the effects of uncertain model parameters (the thicknesses of endothelial surface layers and diffusion coefficients of NO and O2 in muscle tissues and vascular walls) on the model's predictions. Our analysis reveals that small increases in Hct may raise NO availability in the vascular wall. This finding sheds new light on the experimental data that show that the blood circulation responds to systematic increases of Hct in a manner that is consistent with increasing NO production followed by a plateau.


The role of protein interaction motifs in regulating the polarity and clustering of the metabotropic glutamate receptor mGluR1a.
When expressed in cultured hippocampal neurons, the metabotropic glutamate receptor mGluR1a is polarized to dendrites and concentrated at postsynaptic sites. We used a mutational analysis to determine how previously identified protein interaction motifs in the C terminus of mGluR1a contribute to its localization. Our results show that the polyproline motif that mediates interaction with Homer family proteins is critical for the synaptic clustering of mGluR1a. A single point mutation in this motif, which prevents the binding of Homer with mGluR1a, reduced its colocalization with a postsynaptic marker to near-chance levels but did not affect its dendritic polarity. In contrast, deleting the PDZ (postsynaptic density-95/Discs large/zona occludens-1) binding domain, which interacts with Tamalin and Shank, had no effect on synaptic localization. Neither of these protein interaction motifs is important for trafficking to the plasma membrane or for polarization to dendrites. Although deleting the entire C terminus of mGluR1a only modestly reduced its dendritic polarity, this domain was sufficient to redirect an unpolarized reporter protein to dendrites. These observations suggest that mGluR1a contains redundant dendritic targeting signals. Together, our results indicate that the localization of mGluR1a involves two distinct steps, one that targets the protein to dendrites and a second that sequesters it at postsynaptic sites; different protein interactions motifs mediate each step.


Self-referenced interferometry for the characterization of axicon lens quality.
A simple interferometer for the characterization of axicon lenses is presented. The phase cone acquired by a wave propagating through an axicon, when interfered with a collinear reference wave, produces a nearly cylindrically symmetric self-referenced interference pattern from which the distortions of the axicon surface may be readily obtained. Comparison with two-dimensional off-axis interferometry is used to validate the self-referenced technique. The measurements are based on retrieval of the accrued spatial phase distribution from interference fringes with on- and off-axis reference beams and are found to be equivalent. We use the ellipticity of the phase maps to qualify axicon lenses, which are expected to exhibit radial symmetry and engage the self-referential capability of the on-axis method to derive deviation maps that characterize the surface quality of the axicons.


Properties of tetraethylammonium ion-resistant K+ channels in the photoreceptor membrane of the giant barnacle.
After the offset of illumination, barnacle photoreceptors undergo a large hyperpolarization that lasts seconds or minutes. We studied the mechanisms that generate this afterpotential by recording afterpotentials intracellularly from the medial photoreceptors of the giant barnacle Balanus nubilus. The afterpotential has two components with different time-courses: (a) an earlier component due to an increase in conductance to K+ that is not blocked by extracellular tetraethylammonium ion (TEA+) or 3-aminopyridine (3-AP) and (b) a later component that is sensitive to cardiac glycosides and that requires extracellular K+, suggesting that it is due to an electrogenic Na+ pump. The K+ conductance component increases in amplitude with increasing CA++ concentration and is inhibited by extracellular Co++; the Co++ inhibition can be overcome by increasing the Ca++ concentration. Thus, the K+ conductance component is Ca++ dependent. An afterpotential similar to that evoked by a brief flash of light is generated by depolarization with current in the dark and by eliciting Ca++ action potentials in the presence of TEA+ in the soma, axon, or terminal regions of the photoreceptor. The action potential undershoot is generated by an increase in conductance to K+ that is resistant to TEA+ and 3-AP and inhibited by Co++. The similarity in time-course and pharmacology of the hyperpolarization afterpotentials elicited by (a) a brief flash of light, (b) depolarization with current, and (c) an action potential indicates that Ca++-dependent K+ channels throughout the photoreceptor membrane are responsible for all three hyperpolarizing events.


Ultrasound as the first line investigation for midgut malrotation: a UK tertiary centre experience.
To present the first 22-months experience of transitioning to an ultrasound-first pathway for suspected midgut malrotation. An "ultrasound-first" imaging pathway was initiated in October 2021. Twenty-two-months later, a search was undertaken of all <1-year-old patients with "bilious", "malrotation," or "volvulus" as the imaging indication. Reports and images from upper gastrointestinal fluoroscopy (UGI) and ultrasound were reviewed, and diagnoses and outcomes were documented. The search yielded 101 eligible cases between October 2021 and July 2023. Of the patients, 63/101 (62%) had both ultrasound and UGI: 47/63 (75%) ultrasound first, 16/63 (25%) UGI first. Thirty-one per cent (31/101) had ultrasound only and 7/70 (10%) UGI only. The pathway diagnosed 7/8 (88%) infants with midgut malrotation with or without volvulus and one infant who had an inconclusive ultrasound examination with a suspected an internal hernia and who was found to have malrotation volvulus at surgery. Twenty-one infants who had confidently normal ultrasound examinations and who also had UGI all had a normal duodenojejunal flexure position. Ultrasound detected alternative pathology in eight children. Duodenal visualisation improved with time: 6/15 (40%) in the first 6 months to 23/34 (68%) after the first year. The transition to ultrasound as the first diagnostic test for midgut malrotation can be done safely and effectively in a UK centre, which previously relied solely on UGI.


Gabapentin attenuates hyperexcitability in the freeze-lesion model of developmental cortical malformation.
Developmental cortical malformations are associated with a high incidence of drug-resistant epilepsy. The underlying epileptogenic mechanisms, however, are poorly understood. In rodents, cortical malformations can be modeled using neonatal freeze-lesion (FL), which has been shown to cause in vitro cortical hyperexcitability. Here, we investigated the therapeutic potential of gabapentin, a clinically used anticonvulsant and analgesic, in preventing FL-induced in vitro and in vivo hyperexcitability. Gabapentin has been shown to disrupt the interaction of thrombospondin (TSP) with α2δ-1, an auxiliary calcium channel subunit. TSP/α2δ-1 signaling has been shown to drive the formation of excitatory synapses during cortical development and following injury. Gabapentin has been reported to have neuroprotective and anti-epileptogenic effects in other models associated with increased TSP expression and reactive astrocytosis. We found that both TSP and α2δ-1 were transiently upregulated following neonatal FL. We therefore designed a one-week GBP treatment paradigm to block TSP/α2δ-1 signaling during the period of their upregulation. GBP treatment prevented epileptiform activity following FL, as assessed by both glutamate biosensor imaging and field potential recording. GBP also attenuated FL-induced increases in mEPSC frequency at both P7 and 28. Additionally, GBP treated animals had decreased in vivo kainic acid (KA)-induced seizure activity. Taken together these results suggest gabapentin treatment immediately after FL can prevent the formation of a hyperexcitable network and may have therapeutic potential to minimize epileptogenic processes associated with developmental cortical malformations.


Nucleotide sequence of the phosphoglycerate kinase gene from the extreme thermophile Thermus thermophilus. Comparison of the deduced amino acid sequence with that of the mesophilic yeast phosphoglycerate kinase.
Using oligonucleotide probes derived from amino acid sequencing information, the structural gene for phosphoglycerate kinase from the extreme thermophile, Thermus thermophilus, was cloned in Escherichia coli and its complete nucleotide sequence determined. The gene consists of an open reading frame corresponding to a protein of 390 amino acid residues (calculated Mr 41,791) with an extreme bias for G or C (93.1%) in the codon third base position. Comparison of the deduced amino acid sequence with that of the corresponding mesophilic yeast enzyme indicated a number of significant differences. These are discussed in terms of the unusual codon bias and their possible role in enhanced protein thermal stability.


A practical procedure for the determination of electrostatic charges of large molecules.
A practical procedure for the precise determination of electrostatic charges, which are evaluated by fitting the rigorous quantum mechanical molecular electrostatic potential to a monopole-monopole expression, is presented. The proposal of this procedure arises from the study of the minimum requirements necessary to obtain reliable electrostatic charges. Such a study is focused on: (i) the dependence of the electrostatic charges on the set of points where the quantum mechanical and the monopole-monopole molecular electrostatic potentials are fitted; thus, both the influence of the number of points and their distribution in layers located out of the van der Waals radii of the atoms are examined, and (ii) the reliability of the use of fractional models for the evaluation of electrostatic charges of large molecules. Results point out that the optimum number of points is defined by a density of points ranging from 0.45 to 0.60 points/A2 when four layers (separated by 0.2 A) are considered. Nevertheless, the use of only two layers (separated by 0.4 A) for large molecules is recommended, thus enabling one to obtain reliable charges at a reduced computational cost. Moreover, results justify the use of fractional models for the determination of electrostatic charges of extremely large molecules, even when aromatic structures exist.


[Relation between therapeutic efficacy of antianginal preparations in patients with ischemic heart disease and their effect on the rheologic properties of blood].
The effects of a variety of currently-used anti-anginal drugs on major hemorheologic parameters (blood viscosity in the 0.692-2348 s-1 variation rates range, plasma viscosity, erythrocyte and platelet function) and also the hemostatic system were examined in 100 chronic coronary patients during specific treatment courses. The nitrates, beta-blockers (alone or in combinations), cordaron and molsidomin were shown to produce positive effects on blood rheology. A relationship was demonstrated between physical stress tolerance and blood viscosity pattern in propranolol-treated coronary patients. It is suggested that positive hemorheologic effects of anti-anginal drugs may be an important constituent of their therapeutic action and, as such, provide an additional marker of their efficiency in coronary heart disease.


Surgical alternatives for the short bowel syndrome.
Since the introduction of total parenteral nutrition an increasing number of patients are surviving massive intestinal resection. However, the expense, morbidity, and inconvenience of this therapy have created interest in surgical alternatives for the treatment of the short bowel syndrome. The goals of surgical therapy in the short bowel syndrome are to slow intestinal transit, increase the area of absorption, and reduce gastric hyperacidity. Antiperistaltic segments or colon interposition benefit patients with sufficient absorptive area, but rapid intestinal transit. Intestinal valves yield inconsistent results. Recirculating loops are associated with prohibitive morbidity and mortality. Experience with intestinal pacing is limited. Patients with dilated bowel segments may benefit from intestinal tapering or lengthening. Growing neomucosa holds promise but has not been evaluated clinically. Despite recent advances in immunosuppression the results of transplantation remain unsatisfactory. Gastric hyperacidity can be effectively controlled by H2 receptor antagonists. None of the operations for treatment of the short bowel syndrome is sufficiently safe and effective to recommend their routine use. Operations should be performed only on selected patients to achieve specific goals. Although investigation continues, our emphasis should continue to be prevention of intestinal resection and conservation of as much of the intestine as possible when massive resection is necessary.


Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease-a retrospective investigation of 845 patients and its clinical relevance.
Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world. Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections. In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01). Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies.


Hadamard-based image decomposition and compression.
In this paper, we develop a general algorithm for decomposition and compression of grayscale images. The decomposition can be expressed as a functional relation between the original image and the Hadamard waveforms. The dynamic adaptive clustering procedure incorporates potential functions as a similarity measure for clustering as well as a reclustering phase. The latter is a multi-iteration, convergent procedure which divides the inputs into nonoverlapping clusters. These two techniques allow us to efficiently store and transmit a class of half-tone medical images such as magnetic resonance imaging (MRI) of the human brain. Due to the redundant image structure of MRI, obtained after the decomposition and clustering, almost half of the image can be omitted all together. Naturally, the compression rates for this specific type of grayscale image are increased greatly. A run-length coding is performed in order to compress further the retained information from the first two steps. Although all the techniques applied are simple, they represent an efficient way to compress grayscale images. The algorithm exhibits a performance which is competitive and often outperforming some of the methods reported in the literature.


[Feminist theory: the challenge of turning into a paradigm].
From crisis of traditional paradigm and having feminist criticism as an epicentre, this work attempts to present the challenge feminist theory faces for becoming a new paradigm and for that, a bibliographical research is accomplished, sustained by literature regarding to this theme. It is evidentiated that the challenge of being a paradigm in ascension makes this theory to face theoretical, conceptual and methodological problems which need a joined effort to be deepened and solved. However, this theory development depend not only on the academic world but is also linked to changes in social structure for it will more easily emerge, from a more equalitary society, knowledge with no domination of gender.


Long-term follow-up of single-visit pulp revascularisation for the dens evaginatus and dens invaginatus: Cases report.
This article documents cases of single-visit pulp revascularisation for dens evaginatus and dens invaginatus, without using intracranial medicaments or antibiotics, aiming to provide a potentially applicable protocol for pulp revascularisation procedure in a single-visit. Two patients with chief complaints of pain and swelling visited a dental hospital. Radiographs revealed that the causative teeth had an open apex and periapical radiolucency, and the teeth were diagnosed as pulp necrosis and acute apical abscess or symptomatic apical periodontitis. For both cases, single-visit revascularisation was completed without intracanal medicaments or antibiotics. The patients were periodically recalled to evaluate periapical healing after treatment. The apical lesion healed, and the root dentin thickening was observed. The single-visit pulp revascularisation procedure without using specific intracanal medicaments can produce clinically favourable results for these dental anomalies.


Impact of the human immunodeficiency virus epidemic on mortality among adults with tuberculosis in rural South Africa, 1991-1995.
In the Hlabisa district tuberculosis programme, South Africa, the prevalence of human immunodeficiency virus (HIV) infection among adults with tuberculosis increased from 36.0% in 1993 to 65.9% in 1997, and the annual tuberculosis caseload increased from 321 in 1991 to 1250 in 1996. To examine the impact of the HIV epidemic on mortality among adults with tuberculosis from 1991 to 1995. Data were extracted from the control programme database. As the programme started in July 1991, data for this year were combined with those for 1992. All-cause mortality among all those diagnosed with tuberculosis increased by 45.6%, from 9.2% (55/599) in 1991/92 to 13.4% (96/714) in 1995 (P = 0.02). Among smear-positive patients only, mortality increased by 134%, from 4.4% to 10.3% (P = 0.003). The case-fatality rate (CFR) increased in most age groups of both sexes, the largest increase (157.5%) being among women aged 15-34 years. CFR was highest among those with smear-negative disease (24.7% in 1995). In multifactorial analysis, independent risk factors for mortality were increasing age (P = 0.0001), HIV infection (odds ratio [OR] 3.5, 95 % confidence interval [CI] 2.3-5.4), smear-negative disease (OR 2.5, 95%CI 1.8-3.5), and diagnosis in 1995 vs 1991/92 (OR 1.8, 95%CI 1.2-2.7). Mortality among the HIV infected continued to accrue throughout treatment, whereas non-HIV-infected patients that died did so early in treatment. The HIV epidemic is increasing tuberculosis all-cause mortality. As well as having a direct effect on individuals, increased caseloads due to HIV may also contribute to increased mortality by reducing the health system's ability to provide adequate care.


The consumption of ultra-processed products is associated with the best socioeconomic level of the children's families.
The aim of this study was to evaluate the intake of ultra-processed foods and associated factors in prepubertal children. It is a cross-sectional study with 378 children aged 8 and 9 years enrolled in public and private schools in Viçosa-MG. Food intake was assessed by three 24-hour dietary recalls. Dietary data were entered into the Diet Pro® 5i software to quantify energy intake. The Two-Step Cluster technique was used to analyze food consumption groups, with the Stata 13 software package. The foods were grouped and classified as "healthy" and "unhealthy" eating markers. The association between the sociodemographic variables and the groups formed was examined by Poisson Regression. Two food groups were formed: "healthy" and "unhealthy". The caloric intake of ultra-processed foods was lower in the "healthy" group (20.5%) than in the "unhealthy" group (24.1%; P = 0.043). The multivariate model showed that private school children (PR = 1.25, P <0.001), who did not receive Bolsa Familia (PR = 1.13, P = 0.036) and had working mothers (PR = 1.38, P <0.001) had increased probability of unhealthy food consumption. Ultra-processed food intake was associated with greater purchasing power of families of prepubertal children.


Gymnosporangium species on Malus: species delineation, diversity and host alternation.
Gymnosporangium species (Pucciniaceae, Pucciniales, Basidiomycota) are the causal agents of cedar-apple rust diseases, which can lead to significant economic losses to apple cultivars. Currently, the genus contains 17 described species that alternate between spermogonial/aecial stages on Malus species and telial stages on Juniperus or Chamaecyparis species, although these have yet to receive a modern systematic treatment. Furthermore, prior studies have shown that Gymnosporangium does not belong to the Pucciniaceae sensu stricto (s.str.), nor is it allied to any currently defined rust family. In this study we examine the phylogenetic placement of the genus Gymnosporangium. We also delineate interspecific boundaries of the Gymnosporangium species on Malus based on phylogenies inferred from concatenated data of rDNA SSU, ITS and LSU and the holomorphic morphology of the entire life cycle. Based on these results, we propose a new family, Gymnosporangiaceae, to accommodate the genus Gymnosporangium, and recognize 22 Gymnosporangium species parasitic on Malus species, of which G. lachrymiforme, G. shennongjiaense, G. spinulosum, G. tiankengense and G. kanas are new. Typification of G. asiaticum, G. fenzelianum, G. juniperi-virginianae, G. libocedri, G. nelsonii, G. nidus-avis and G. yamadae are proposed to stabilize the use of names. Morphological and molecular data from type materials of 14 Gymnosporangium species are provided. Finally, morphological characteristics, host alternation and geographical distribution data are provided for each Gymnosporangium species on Malus.


Hypoglycemic effect of a leaf extract of Pseuderanthemum palatiferum (Nees) Radlk. in normal and streptozotocin-induced diabetic rats.
Pseuderanthemum palatiferum (Nees) Radlk (Acanthaceae) was first found in Northern Vietnam and expanded throughout the country including the Mekong Delta region. The leaves of this plant are recommended in folk medicine of Vietnam and Thailand for promoting and treating various diseases including hypertension, diarrhea, arthritis, hemorrhoids, stomachache, tumors, colitis, bleeding, wounds, constipation, flu, colon cancer, nephritis, and diabetes. The hypoglycemic effect of an 80% ethanolic leaf extract from the leaves of Pseuderanthemum palatiferum (PPE) was investigated in normal and streptozotocin (STZ)-induced diabetic rats. The PPE was administered daily and orally to the rats at the doses of 250, 500, and 1000 mg/kg body weight (b.w.) for 14 days. The levels of fasting plasma glucose (FPG), serum insulin, and biochemical data such as blood urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and alkaline phosphatase (ALP) were evaluated. The hypoglycemic effect of PPE was compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). FPG and serum insulin in normal rats were not significantly different from the control and test groups in all dosages. The treated diabetic rats which had received PPE and glibenclamide showed significantly (p<0.05) decreased FPG and increased serum insulin levels at the end of the experiment. The hypoglycemic effect of PPE at the dose of 250 mg/kg b.w. was significantly (p<0.05) more effective than that of glibenclamide. The serum insulin in PPE fed diabetic rats at the dose of 250 mg/kg b.w. was not different from those which had received glibenclamide, and this dose was significantly (p<0.05) more effective than PPE at the doses of 500 and 1000 mg/kg b.w. while PPE increased HDL and decreased TC, TG, LDL, BUN and ALP in the diabetic rats. PPE has a beneficial effect in hyperglycemic rats and may prevent the complication of diabetes.


IL-3 augments TCR-mediated responses of type 2 CD4 T cells.
A subset of type 2, but not type 1, CD4 T cell clones expresses IL-3R and can be stimulated by IL-3. Expression of IL-3R on these type 2 T cell clones is induced by TCR stimulation, and subsequent stimulation by IL-3 augmented the proliferation of and IL-4 production by these cells. This augmented response is inhibited by anti-IL-4 mAb, suggesting the involvement of IL-4 in this response. In place of TCR stimulation, treatment of these type 2 CD4 T cell clones with PMA rendered them responsive to further stimulation of proliferation by IL-3, indicating the cooperation between the IL-3R-elicited signals and PKC-mediated signals in stimulating proliferation. Although the augmentation of the TCR-mediated proliferative response by IL-3 was mainly due to the increased production of IL-4, we also demonstrated the presence of IL-4-independent mechanism mediating the response to IL-3. In situ, we found that splenic T cells could be induced to respond to Il-3 by TCR stimulation. Thus, IL-3 can stimulate a specific population of T cells and influence the immune response.


Midostaurin: a magic bullet that blocks mast cell expansion and activation.
Clinically relevant features in patients with systemic mastocytosis (SM) include the cosmetic burden of lesional skin, mediator-related symptoms, and organ damage resulting from mast cell (MC) infiltration in advanced forms of SM. Regardless of the SM variant, expansion of neoplastic MC in the skin and other organs is triggered by mutant forms of KIT, the most prevalent being D816V. Activation of MC with subsequent release of chemical mediators is often caused by IgE-dependent mechanisms in these patients. Midostaurin, also known as PKC412, blocks the kinase activity of wild-type KIT and KIT D816V, counteracts KIT-dependent growth of neoplastic MC, and inhibits IgE-dependent mediator secretion. Based on this activity-profile, the drug has been used for treatment of patients with advanced SM. Indeed, encouraging results have been obtained with the drug in a recent multi-center phase II trial in patients with advanced SM, with an overall response rate of 60% and a substantial decrease in the burden of neoplastic MC in various organs. Moreover, midostaurin improved the overall survival and relapse-free survival in patients with advanced SM compared with historical controls. In addition, midostaurin was found to improve mediator-related symptoms and quality of life, suggesting that the drug may also be useful in patients with indolent SM suffering from mediator-related symptoms resistant to conventional therapies or those with MC activation syndromes. Ongoing and future studies will determine the actual value of midostaurin-induced MC depletion and MC deactivation in these additional indications.


On the structural features of fiber suspensions in converging channel flow.
The structural features of fiber suspensions are dependent on the fiber alignment in the flows. In this work the orientation distribution function and orientation tensors for semi-concentrated fiber suspensions in converging channel flow were calculated, and the evolutions of the fiber alignment and the bulk effective viscosity were analyzed. The results showed that the bulk stress and the effective viscosity were functions of the rate-of-strain tensor and the fiber orientation state; and that the fiber suspensions evolved to steady alignment and tended to concentrate to some preferred directions close to but not same as the directions of local streamlines. The bulk effective viscosity depended on the product of Reynolds number and time. The decrease of effective viscosity near the boundary benefited the increase of the rate of flow. Finally when the fiber alignment went into steady state, the structural features of fiber suspensions were not dependent on the Reynolds number but on the converging channel angle.


Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities.
Environmental factors have been associated with transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on severity of influenza infection. We applied a Poisson regression model to the mortality data of two Chinese metropolitan cities located within the subtropical zone, to calculate the influenza associated excess mortality risks during the periods with different levels of temperature and humidity. The results showed that high absolute humidity (measured by vapor pressure) was significantly (p < 0.05) associated with increased risks of all-cause and cardiorespiratory deaths, but not with increased risks of pneumonia and influenza deaths. The association between absolute humidity and mortality risks was found consistent among the two cities. An increasing pattern of influenza associated mortality risks was also found across the strata of low to high relative humidity, but the results were less consistent for temperature. These findings highlight the need for people with chronic cardiovascular and respiratory diseases to take extra caution against influenza during hot and humid days in the subtropics and tropics.


[Diagnostic image (2). (Gas gangrene of diabetic foot)].
A 63-year-old woman with diabetes mellitus type 2 and an ulcer on the foot developed gas gangrene and was treated with antibiotics and surgical excision. She died before she could be treated with hyperbaric oxygen.


An On-Treatment Analysis of the MARQUIS Study: Interventions to Improve Inpatient Medication Reconciliation.
It is unclear which medication reconciliation interventions are most effective at reducing inpatient medication discrepancies. Five United States hospitals' interdisciplinary quality improvement (QI) teams were virtually mentored by QI-trained physicians. Sites implemented one to seven evidence-based interventions in 791 patients during the 25-month implementation period. Three interventions were associated with significant decreases in potentially harmful discrepancy rates: (1) defining clinical roles and responsibilities, (2) training, and (3) hiring staff to perform discharge medication reconciliation. Two interventions were associated with significant increases in potentially harmful discrepancy rates: training staff to take medication histories and implementing a new electronic health record (EHR). Hospitals should focus first on hiring and training pharmacy staff to assist with medication reconciliation at discharge and delineating roles and responsibilities of clinical staff. We caution hospitals implementing a large vendor EHR, as medication discrepancies may increase. Finally, the effect of medication history training on discrepancies needs further study.


Catechin, green tea component, causes caspase-independent necrosis-like cell death in chronic myelogenous leukemia.
Management strategies of chronic phase chronic myelogenous leukemia (CML) have been revolutionized due to the discovery of a selective tyrosine kinase inhibitor, imatinib (Gleevec, STI571), which is substantially improving median survival. However, emergence of imatinib-resistance has put up a serious problem that requires novel treatment methods. Catechins, polyphenolic compounds in green tea, are gathering much attention due to their potential antitumor effects. So far (-)-epigallocatechin-3-gallate (EGCG), the most abundant component of catechin, has been shown to cause typical apoptosis in several tumor cell lines in most cases through activation of caspases. In this study, we showed that EGCG predominantly caused necrosis-like cell death via a caspase-independent mechanism in CML cells, K562 and C2F8, whereas imatinib induced the typical apoptotic cell death. Moreover, this caspase-independent cell death partially mediated the release of apoptosis-inducing factor, AIF, and serine protease, HtrA2/Omi, from the mitochondria to cytosol. In addition, EGCG enhanced the imatinib-induced cell death (P < 0.01) resulting in additive cell death in K562 cells and EGCG alone, effectively reduced the viability of imatinib-resistant K562 cells (P < 0.01). Catechin is a possible candidate for an antitumor agent that causes cell death in CML cells via a caspase-independent mechanism.


Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta.
The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization.


Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population.
Drug policy makers continuously face a changing pattern of drug use, i.e. new drugs appear on the market, the popularity of certain drugs changes or drugs are used in another way or another combination. For legislative purposes, drugs have mostly been classified according to their addictive potency. Such classifications, however, lack a scientific basis. The present study describes the results of a risk assessment study where 19 recreational drugs (17 illicit drugs plus alcohol and tobacco) used in the Netherlands have been ranked by a Dutch expert panel according to their harm based on the scientific state of the art. The study applies a similar approach as recently applied by Nutt et al. [Lancet 2007;369:1047-1053], so that the results of both studies could be compared. The harm indicators scored are acute and chronic toxicity, addictive potency and social harm. The aim of this study is to evaluate whether the legal classification of drugs in the Netherlands corresponds with the ranking of the drugs according to their science-based ranking of harm. Based on the results, recommendations are formulated about the legal classification of recreational drugs at national and international level which serves a rational approach for drug control.


CESCR: CP-ABE for efficient and secure sharing of data in collaborative ehealth with revocation and no dummy attribute.
With the rapid advancement of information and communication technologies, there is a growing transformation of healthcare systems. A patient's health data can now be centrally stored in the cloud and be shared with multiple healthcare stakeholders, enabling the patient to be collaboratively treated by more than one healthcare institution. However, several issues, including data security and privacy concerns still remain unresolved. Ciphertext-policy attribute-based encryption (CP-ABE) has shown promising potential in providing data security and privacy in cloud-based systems. Nevertheless, the conventional CP-ABE scheme is inadequate for direct adoption in a collaborative ehealth system. For one, its expressiveness is limited as it is based on a monotonic access structure. Second, it lacks an attribute/user revocation mechanism. Third, the computational burden on both the data owner and data users is linear with the number of attributes in the ciphertext. To address these inadequacies, we propose CESCR, a CP-ABE for efficient and secure sharing of health data in collaborative ehealth systems with immediate and efficient attribute/user revocation. The CESCR scheme is unbounded, i.e., it does not bind the size of the attribute universe to the security parameter, it is based on the expressive and non-restrictive ordered binary decision diagram (OBDD) access structure, and it securely outsources the computationally demanding attribute operations of both encryption and decryption processes without requiring a dummy attribute. Security analysis shows that the CESCR scheme is secure in the selective model. Simulation and performance comparisons with related schemes also demonstrate that the CESCR scheme is expressive and efficient.


Porcine sperm zona binding ability as an indicator of fertility.
The escalated use of artificial insemination in swine has increased the importance of determining fertility of a semen sample before it is used. Multiple laboratory assays have been developed to assess fertilizing potential but they have yielded inconsistent results. This experiment sought to determine the relationship between in vitro competitive zona binding ability and in vivo fertility based on heterospermic inseminations and paternity testing. The zona pellucida binding ability and fertility of sperm from 15 boars was assessed by comparing sperm from one boar with sperm from other individual boars in a pairwise fashion using four ejaculates. The relationship of zona binding ability to the mean number of piglets sired per litter for each boar as well as historic fertility data (litter size and farrowing rate) was assessed. The in vitro competition assay consisted of labeling sperm from each boar of the pair with a different fluorophore and incubating an equal number of sperm from each boar in the same droplet with porcine oocytes. The competitive assay was highly effective in ranking boars by zona binding ability (R2=0.94). Paternity testing using microsatellite markers was used to determine the mean number of piglets sired per litter for each boar during heterospermic inseminations. The pairwise heterospermic insemination assay was effective in ranking boar fertility (R2=0.59). Using historical data from these boars, average litter size and farrowing rate were correlated (r=0.81, p<0.001). However, zona binding ability was not significantly correlated with historic farrowing rate data or historic average litter size. Boar sperm zona binding ability was also not correlated significantly with the mean number of piglets sired per litter following heterospermic insemination. But the number of piglets sired by each boar was related to a combination of zona binding ability, sperm motility, normal morphology, acrosomal integrity, and the presence of distal droplets (R2=0.70). These results suggest that zona binding ability is not an accurate predictor of fertilizing ability when used alone; however, when coupled with other sperm assessments, fertility may be predicted successfully.


Time course of saline-induced recovery of the gustatory system in sodium-restricted rats.
Placing pregnant rats on a Na(+)-restricted diet (0.03% NaCl) results in greatly reduced chorda tympani nerve responses to Na+ stimuli in the offspring. Normal responses can be permanently restored by providing offspring one-time access to saline. We tested whether saline-induced recovery occurs in taste receptor cells present at the time of saline intake. Chorda tympani responses were recorded 2 h, 6 h, 24 h, 10 days, and 20 days after saline ingestion. Chorda tympani Na+ responses from Na(+)-restricted rats at 2 h, 6 h, 24 h, and 10 days after saline intake were comparable to responses from control Na(+)-restricted rats. Twenty days after saline consumption, responses to Na+ were significantly elevated compared with control Na(+)-restricted rats. The results indicate that extant taste receptor cells are not substantially influenced by the saline ingestion. Instead, the delayed recovery suggests that taste receptor stem cells exclusively are influenced by saline intake.


Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis.
Tuberculosis remains the greatest cause of death worldwide due to a single pathogen. In order to identify the genes required for the pathogenicity of Mycobacterium tuberculosis, a functional genomic approach was developed. A library of signature-tagged transposon mutants of this bacterium was constructed and screened for those affected in their multiplication within the lungs of mice. From 1927 mutants tested, 16 were attenuated for their virulence. The insertions harboured by the selected mutants were mapped on the M. tuberculosis genome and most of the mutated loci appeared to be involved in lipid metabolism or transport across the membrane. Four independent mutations identified a cluster of virulence genes located on a 50 kb chromosomal region. These genes might be involved in the production of phthiocerol and phenolphthiocerol derivatives, a group of molecules restricted to eight mycobacterial species, seven of them being either strict or opportunistic pathogens. The interaction of five mutant strains with mouse bone marrow macrophages was investigated. These five mutants were still able to multiply in this cell type. However, in three cases, there was a growth defect in comparison with the wild-type strain. The other two strains exhibited no clear difference from the virulent strain, MT103, in this model. This study, which is the first global research of virulence factors of M. tuberculosis, opens the way to a better understanding of the molecules that are key players in the interaction of this pathogen with its host.


Heteroduplex DNA formation is associated with replication and recombination in poxvirus-infected cells.
Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells and recombine at high frequencies. Calcium phosphate precipitates were used to cotransfect Shope fibroma virus-infected cells with different DNA substrates and the recombinant products assayed by genetic and biochemical methods. We have shown previously that bacteriophage lambda DNAs can be used as substrates in these experiments and recombinants assayed on Escherichia coli following DNA recovery and in vitro packaging. Using this assay it was observed that 2-3% of the phage recovered from crosses between point mutants retained heteroduplex at at least one of the mutant sites. The reliability of this genetic analysis was confirmed using DNA substrates that permitted the direct detection of heteroduplex molecules by denaturant gel electrophoresis and Southern blotting. It was further noted that heteroduplex formation coincided with the onset of both replication and recombination suggesting that poxviruses, like certain bacteriophage, make no clear biochemical distinction between these three processes. The fraction of heteroduplex molecules peaked about 12-hr postinfection then declined later in the infection. This decline was probably due to DNA replication rather than mismatch repair because, while high levels of induced DNA polymerase persisted beyond the time of maximal heteroduplex recovery, we were unable to detect any type of mismatch repair activity in cytoplasmic extracts. These results suggest that, although heteroduplex molecules are formed during the progress of poxviral infection, gene conversion through mismatch repair probably does not produce most of the recombinants. The significance of these observations are discussed considering some of the unique properties of poxviral biology.


A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation.
The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here, we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes, we build phylogenies and time lines of domains at fold and fold superfamily levels of structural complexity. These time lines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the time line revealed that aerobic metabolism emerged about 2.9 billion years (giga-annum; Ga) ago and expanded during a period of about 400 My, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting that oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool.


Fetal exposure to low protein maternal diet alters the susceptibility of young adult rats to sulfur dioxide-induced lung injury.
The maternal diet is an important determinant of glutathione-related metabolism in rats. Glutathione (GSH) may play a major role in the detoxification of sulfur dioxide (SO2) within the lungs. The effects of fetal exposure to a low protein maternal diet upon later susceptibility to pulmonary injury induced by chronic SO2 exposure were evaluated in young adult rats. Pregnant rats were fed purified diets containing 180 g casein/kg (control diet) or 120, 90 or 60 g casein/kg (experimental diets). After parturition, all dams were fed a standard non-purified diet (189 g protein/kg diet). The pups thus differed only in terms of protein nutrition during gestation. At seven wk of age the male pups were housed in either room air or 286 microg SO2/m3 for 5 h/d during a 28-d period. At the end of the final SO2 treatment period, the rats exposed to 90 or 60 g casein/kg diets in utero exhibited significantly greater pulmonary injury, as assessed by bronchoalveolar lavage, than did those exposed to control diet in utero. Significant maternal diet-induced differences in activities of enzymes of the gamma-glutamyl cycle were noted in the lungs and livers of rats which had not undergone SO2 treatment. Furthermore, the response of these enzyme activities to SO2 treatment was determined by prior exposure to the maternal diet. SO2-treated rats exposed to control diet (180 g casein/kg) and low protein diet (60 g casein/kg), but not those exposed to 120 or 90 g casein/kg diets, tended to augment the activities, relative to rats not treated with SO2, of enzymes which maintain tissue GSH status either through synthesis or recycling. Differences in susceptibility to SO2-induced tissue injury may be related to programming of GSH metabolism by the maternal diet. Alternatively, impaired immune and acute phase responses to an inflammatory insult may account for a failure to resolve initial SO2-induced injury in rats exposed to low protein maternal diets.


Transderm scopolamine efficacy related to time of application prior to the onset of motion.
We evaluated Transdermal Scopolamine related to the time of application prior to the onset of motion. In this study 44 subjects participated. The first group applied the transdermal disc within 4 h and the second group 8 h or more prior to the onset of motion. We observed a significant decrease in the incidence and the degree of motion sickness for the group with at least 8 h of scopolamine application prior to sea travel. Therefore, the transdermal scopolamine system should be applied at least 8 h before potentially disturbing motion to provide adequate prophylaxis against motion sickness. We found no significant difference in motion sickness susceptibility between men and women, in contrast to earlier reports.


[Postreplicative DNA repair in UV-sensitive Chinese hamster cell clones].
The postreplication repair (PRR) of DNA has been studied in UV-irradiated (10 J/m2) and carcinogen (7-bromomethylbenz(alpha)anthracene -- BMBA) treated (1.65-3.3) 10(-6) M Chinese hamster clones with different UV-sensitivity. Ultracentrifugation in alkaline sucrose gradients has been used. Compared to the UV-resistent clone V-79, the UV-sensitive clone CHS2 displayed a lower effectivity of PRR of DNA after both UV-irradiation and carcinogen treatment, by 6 and 10 times, resp. Thus, there is a positive correlation between lethal and mutagenic effects of UV-irradiation and the effectivity of PRR of DNA. The same conclusion is apparently true in the case of carcinogen 7-BMBA treated Chinese hamster cells.


Cellulosimicrobium cellulans aortic prosthetic valve endocarditis.
Invasive infections due to Cellulosimicrobium spp. (a Gram-positive coryneform) are extremely rare. Only a few cases of bloodstream infections and endocarditis have been described, as bacteraemia due to coryneforms is usually discarded as blood culture contamination. A 66-year-old female, with a history of aortic valve replacement, presented with fever, left leg purpura and acute kidney injury. Multiple repeated blood cultures were positive for Cellulosimicrobium cellulans , and targeted therapy was started. At first, endocarditis was excluded by echocardiograms, and the acute nephritis was interpreted as an atypical presentation of Henoch-Shönlein purpura. High-dose prednisone was started, and after 10 weeks the patient presented again with fever, mental confusion and acute left arm ischaemia. A subsequent echocardiogram and radiolabelled leukocyte scintigraphic evaluation revealed aortic prosthetic valve endocarditis with periprosthetic abscess and arterial brachial thrombosis. The patient deceased, and the autoptic examination confirmed an aortic valve periprosthetic abscess and revealed multiple arterial thromboses and septic embolisms in the kidneys, brain, spleen and myocardium. Isolation of coryneform bacteria on blood culture should not always be discarded as blood culture contamination. In the case of endocarditis due to Cellulosimicrobium spp., the removal of any prosthetic material, along with prolonged in vitro active antimicrobial therapy, should be pursued in order to reduce persistence or relapses of infection.


POWERDRESS and diversified expression of the MIR172 gene family bolster the floral stem cell network.
Termination of the stem cells in the floral meristem (also known as floral determinacy) is critical for the reproductive success of plants, and the molecular activities regulating floral determinacy are precisely orchestrated during the course of floral development. In Arabidopsis thaliana, regulators of floral determinacy include several transcription factor genes, such as APETALA2 (AP2), AGAMOUS (AG), SUPERMAN (SUP), and CRABSCLAW (CRC), as well as a microRNA (miRNA), miR172, which targets AP2. How the transcription factor and miRNA genes are coordinately regulated to achieve floral determinacy is unknown. A mutation in POWERDRESS (PWR), a previously uncharacterized gene encoding a SANT-domain-containing protein, was isolated in this study as an enhancer of the weakly indeterminate ag-10 allele. PWR was found to promote the transcription of CRC, MIR172a, b, and c and/or enhance Pol II occupancy at their promoters, without affecting MIR172d or e. A mutation in mature miR172d was additionally found to enhance the determinacy defects of ag-10 in an AP2-dependent manner, providing direct evidence that miR172d is functional in repressing AP2 and thereby contributes to floral determinacy. Thus, while PWR promotes floral determinacy by enhancing the expression of three of the five MIR172 members as well as CRC, MIR172d, whose expression is PWR-independent, also functions in floral stem cell termination. Taken together, these findings demonstrate how transcriptional diversification and functional redundancy of a miRNA family along with PWR-mediated co-regulation of miRNA and transcription factor genes contribute to the robustness of the floral determinacy network.


Is King-Devick Testing, Compared With Other Sideline Screening Tests, Superior for the Assessment of Sports-related Concussion?: A Critically Appraised Topic.
Concussion affects almost 4 million individuals annually. There are many sideline screening tools available to assist in the detection of sports-related concussion. The King-Devick (K-D) test in association with Mayo Clinic utilizes rapid number naming to test saccadic eye movements in order to screen for concussion. An ideal screening tool for concussion would correctly identify all athletes with active concussion. The accuracy of K-D testing compared with other sideline screening tools is undetermined. To critically assess current evidence regarding the utility of K-D testing as a sideline screening tool for acute concussion and compare K-D testing to other sideline concussion assessments. The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of concussion neurology and neuro-ophthalmology. A recent meta-analysis was selected for critical appraisal. Cohorts analyzing athletes with sports-related concussion were selected, and utilized K-D testing as the main baseline and sideline assessment of concussion. K-D testing was found to have a high sensitivity and specificity for detecting concussion when there was worsening from baseline. K-D testing has high sensitivity and specificity for detecting sideline concussion. Compared with other sideline screening tools that do not include vision testing, it has greater accuracy. Screening for concussion is optimized when multiple testing modalities are used in conjunction.


Labor force participation and health-related quality of life in HIV-positive men who have sex with men: the Multicenter AIDS Cohort Study.
Too many people with HIV have left the job market permanently and those with reduced work capacity have been unable to keep their jobs. There is a need to examine the health effects of labor force participation in people with HIV. This study presents longitudinal data from 1,415 HIV-positive men who have sex with men taking part in the Multicenter AIDS Cohort Study. Generalized Estimating Equations show that employment is associated with better physical and mental health quality of life and suggests that there may be an adaptation process to the experience of unemployment. Post hoc analyses also suggest that people who are more physically vulnerable may undergo steeper health declines due to job loss than those who are generally healthier. However, this may also be the result of a selection effect whereby poor physical health contributes to unemployment. Policies that promote labor force participation may not only increase employment rates but also improve the health of people living with HIV.


Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells.
Proteasome inhibitors represent a novel class of antitumor agents with pre-clinical and clinical evidence of activity against hematologic malignancies and solid tumors. However, emerging evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, thus it seems plausible that the activation of survival signaling cascades might compromise their antitumoral effects. Peroxiredoxins (PRDXs) are a family of thiol-containing peroxidases identified primarily by their ability to remove cellular hydroperoxides. The function of PRDX1 in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Another important finding is that aberrant upregulation of PRDX1 has been discovered in various cancers. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase that is regulated under conditions of cellular stress. ASK1 phosphorylates c-Jun N-terminal kinase and p38 MAPK, and elicits an apoptotic response. ASK1 activity is regulated at multiple levels, one of which is through interaction with PRDX1. In this study, for the first time we report that upregulation of PRDX1 expression was found in thyroid cancer cells treated with proteasome inhibitors, and PRDX1 knockdown resulted in accelerated proteasome inhibitor-induced cell death. In addition, we demonstrated that ASK1 activity was implicated in the PRDX1-dependent response of thyroid cancer cells to proteasome inhibitor-mediated cell death.


Green finance and the synergy of ESGGI performance of Chinese companies: Does green concern matter?
This study aims to investigate green finance's impact on the synergy between ESG and green innovation (ESGGI) performance and examine the potential influence played by stakeholders' green concerns on this impact. Hence, we calculated the synergy of ESGGI performance based on the entropy method and the coupled coordination degree model and conducted regression analyses on the data of 1143 Chinese companies from 2012 to 2020. The results reveal a remarkable inverted U-shaped relationship between green finance and the synergy of ESGGI performance. Additionally, the green concerns of the government and the media can efficiently moderate green finance's impact on the synergy of ESGGI performance. Further tests show that green finance's impact on the synergy of ESGGI performance of SOEs, HPEs, and HTEs is more significant. This paper demonstrates an association between green finance and the synergy of ESGGI performance, which yields new insights for companies to implement green transformation and sustainable development.


Endoglin in liver fibrogenesis: Bridging basic science and clinical practice.
Endoglin, also known as cluster of differentiation CD105, was originally identified 25 years ago as a novel marker of endothelial cells. Later it was shown that endoglin is also expressed in pro-fibrogenic cells including mesangial cells, cardiac and scleroderma fibroblasts, and hepatic stellate cells. It is an integral membrane-bound disulfide-linked 180 kDa homodimeric receptor that acts as a transforming growth factor-β (TGF-β) auxiliary co-receptor. In humans, several hundreds of mutations of the endoglin gene are known that give rise to an autosomal dominant bleeding disorder that is characterized by localized angiodysplasia and arteriovenous malformation. This disease is termed hereditary hemorrhagic telangiectasia type I and induces various vascular lesions, mainly on the face, lips, hands and gastrointestinal mucosa. Two variants of endoglin (i.e., S- and L-endoglin) are formed by alternative splicing that distinguishes from each other in the length of their cytoplasmic tails. Moreover, a soluble form of endoglin, i.e., sol-Eng, is shedded by the matrix metalloprotease-14 that cleaves within the extracellular juxtamembrane region. Endoglin interacts with the TGF-β signaling receptors and influences Smad-dependent and -independent effects. Recent work has demonstrated that endoglin is a crucial mediator during liver fibrogenesis that critically controls the activity of the different Smad branches. In the present review, we summarize the present knowledge of endoglin expression and function, its involvement in fibrogenic Smad signaling, current models to investigate endoglin function, and the diagnostic value of endoglin in liver disease.


Genetic knockdown of a single organic anion transporter alters the expression of functionally related genes in Malpighian tubules of Drosophila melanogaster.
Insects excrete a wide variety of toxins via the Malpighian (renal) tubules. Previous studies have implicated three transporters in the secretion of the organic anion (OA) methotrexate (MTX) by the Drosophila Malpighian tubule: Drosophila multidrug resistance-associated protein (dMRP, CG6214), a multidrug efflux transporter (MET, CG30344), and an organic anion transporting polypeptide 58Dc (OATP58Dc, CG3380). RNA interference (RNAi) knockdown and P-element insertion mutation of single OA transporter genes were used to evaluate the importance of these three putative transporters in the secretion of MTX by the Malpighian tubules of Drosophila melanogaster. A major finding is that genetic knockdown of a single OA transporter gene leads to reductions in the expression of at least one other OA transporter gene and in secretion of MTX by Malpighian tubules isolated from flies reared on a standard diet. The pattern of changes indicates that decreases in MTX secretion do not correspond to decreases in dMRP expression in all of the RNAi lines. Genetic knockdown of a single OA transporter gene also alters the extent of upregulation of multiple OA transporter genes in the tubules in response to dietary MTX. Knockdown of dMRP is associated with a decrease in MET expression but an increase in OATP expression when flies are reared on MTX-enriched diet. Our results indicate that dMRP and MET are not the dominant MTX transporters in the tubules when flies are reared on MTX-enriched diets. At least one additional transporter, and possibly OATP, are required for MTX secretion. The implications of our results for studies using genetic knockdown techniques to identify OA transporters in whole tissues such as Malpighian tubules are discussed.


Pulmonary involvement in human T-cell lymphotropic virus type-I uveitis: T-lymphocytosis and high proviral DNA load in bronchoalveolar lavage fluid.
The ocular manifestation of human T-cell lymphotropic virus type I (HTLV-I) infection has been recognized as a new clinical entity termed HTLV-I uveitis. In order to determine whether HTLV-I uveitis is associated with lymphocyte alveolitis, bronchoalveolar lavage (BAL) was carried out in 11 patients with HTLV-I uveitis, five asymptomatic HTLV-I carriers, 11 HTLV-I-negative patients with ocular sarcoidosis, and nine normal control subjects seronegative for HTLV-I. Six of the 11 patients with HTLV-I uveitis showed increased total cell counts, and T-lymphocytosis in BAL fluid. CD4+/CD8+ ratios of T-lymphocytes were decreased in three of these patients, and normal in three other patients. Such abnormalities of the lung were not found in asymptomatic HTLV-I carriers, and in normal control subjects. BAL findings in HTLV-I uveitis differed from those of patients with sarcoidosis in terms of the lymphocytic component. Interestingly, it was found that there was an increase of HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMC) from seven patients with HTLV-I uveitis, and in the BAL cells from four patients with pulmonary involvement. These results provide further evidence in terms of HTLV-I tropism for the lung, and suggest that a systemic and local increase of HTLV-I proviral DNA load plays an important role in the pathogenesis of lymphocyte alveolitis in patients with HTLV-I uveitis.


Molecular analysis of a novel intragenic deletion in GPC3 in three cousins with Simpson-Golabi-Behmel syndrome.
Simpson-Golabi-Behmel syndrome (SGBS) is characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features intellectual disability (ID) of variable degree, and an increased risk for embryonal tumors. SGBS is X-linked recessive and caused by deletions, duplications, and point mutations in GPC3, encoding a membrane associated cell surface heparan sulfate proteoglycan named glypican 3. GPC3 plays essential roles in the regulation of cell growth signaling and cell division. Here, we report on a family with three affected cousins who show variable clinical signs of SGBS and ID. Initial microarray-CGH revealed a deletion of approximately 30-50 kb that includes at least one exon of GPC3. By subsequent Sanger sequencing of genomic DNA we could map the chromosomal break points to define a deletion size of 43,617 bp including exons 5 and 6 of the GPC3 gene. RT-PCR analysis on RNA derived from whole blood could further confirm the deletion of both exons on transcript level. This loss of two exons results in a frameshift and a premature stop of translation. Based on our results we have established a breakpoint spanning PCR that could identify the mutation in the mothers and grandmother of the patients. Thus, we provided a molecular test that allows accurate genetic counselling and prenatal diagnosis for this family.


Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM.
Reliability, the consistency of a test or measurement, is frequently quantified in the movement sciences literature. A common metric is the intraclass correlation coefficient (ICC). In addition, the SEM, which can be calculated from the ICC, is also frequently reported in reliability studies. However, there are several versions of the ICC, and confusion exists in the movement sciences regarding which ICC to use. Further, the utility of the SEM is not fully appreciated. In this review, the basics of classic reliability theory are addressed in the context of choosing and interpreting an ICC. The primary distinction between ICC equations is argued to be one concerning the inclusion (equations 2,1 and 2,k) or exclusion (equations 3,1 and 3,k) of systematic error in the denominator of the ICC equation. Inferential tests of mean differences, which are performed in the process of deriving the necessary variance components for the calculation of ICC values, are useful to determine if systematic error is present. If so, the measurement schedule should be modified (removing trials where learning and/or fatigue effects are present) to remove systematic error, and ICC equations that only consider random error may be safely used. The use of ICC values is discussed in the context of estimating the effects of measurement error on sample size, statistical power, and correlation attenuation. Finally, calculation and application of the SEM are discussed. It is shown how the SEM and its variants can be used to construct confidence intervals for individual scores and to determine the minimal difference needed to be exhibited for one to be confident that a true change in performance of an individual has occurred.


The mode of evolution of aggregation pheromones in Drosophila species.
Aggregation pheromones are used by fruit flies of the genus Drosophila to assemble on breeding substrates, where they feed, mate and oviposit communally. These pheromones consist of species-specific blends of chemicals. Here, using a phylogenetic framework, we examine how differences among species in these pheromone blends have evolved. Theoretical predictions, genetic evidence, and previous empirical analysis of bark beetle species, suggest that aggregation pheromones do not evolve gradually, but via major, saltational shifts in chemical composition. Using pheromone data for 28 species of Drosophila we show that, unlike with bark beetles, the distribution of chemical components among species is highly congruent with their phylogeny, with closely related species being more similar in their pheromone blends than are distantly related species. This pattern is also strong within the melanogaster species group, but less so within the virilis species group. Our analysis strongly suggests that the aggregation pheromones of Drosophila exhibit a gradual, not saltational, mode of evolution. We propose that these findings reflect the function of the pheromones in the ecology of Drosophila, which does not hinge on species specificity of aggregation pheromones as signals.


Reduction in chlorophyll content without a corresponding reduction in photosynthesis and carbon assimilation enzymes in yellow-green oil yellow mutants of maize.
The photosynthetic properties of a yellow lethal mutant, Oy/oy, and two yellow-green mutants of maize which are allelic (a homozygous recessive oy/oy and a heterozygous dominant Oy/+) were examined. Although Oy/oy had little or no chlorophyll or capacity for CO2 fixation compared to normal siblings, it had 28% as much ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) activity, and from 40% to near normal activities of C4 cycle enzymes.Both yellow-green mutants had only half as much chlorophyll per leaf area as normal green seedlings in greenhouse-grown plants in winter and spring. However, the absorbance of light by the mutants was relatively high, as their transmittance was only 5 to 8% greater than normal leaves. In winter-grown greenhouse plants, the activities of Rubisco and several C4 cycle enzymes in the mutants were unaffected and similar to those of normal seedlings on a leaf area basis. After allowing for small differences in leaf absorbance, the light response curves for photosynthesis in the mutants were similar on a leaf area basis but much higher on a chlorophyll basis than those of the normal seedlings. In spring-grown greenhouse plants the enzyme activities and photosynthesis rates were about 30% lower per leaf area in the yellow-green mutant leaves compared to the wild type. The maximum carboxylation efficiency (measured under low CO2 and 1000 μmol quanta m(-2) s(-1)) in the mutants and normal leaves was similar on a Rubisco protein basis. The results indicate that maize can undergo a 50% reduction in chlorophyll content without a corresponding reduction in enzymes of carbon assimilation, and still maintain a high capacity for photosynthesis.


Subcellular distribution of 2?,3?-cyclic nucleotide-3?-phosphodiesterase in cat peripheral nerve.
Subcellular distribution of 2?,3?-cyclic nucleotide-3?-phosphodiesterase (CNPase) in desheathed, saline perfused cat sciatic nerve is reported. CNPase specific activity was enriched in the total particulate (P(2)) fraction and was low in the soluble (S(2)) fraction. "Light-myelin" floating above the 0.60 M sucrose phase had the highest CNPase activity, 2.5-fold over the crude homogenate (CH). By contrast, enzyme activity in "heavy myelin" floating above the 0.85 M sucrose interface was equal to that of the CH and accounted for only 12% of total activity. CNPase activity in the membranes floating above the 0.25 and 0.60 and 0.85 M sucrose phases comprised nearly 70% of the total CNPase activity. The "light myelin" fraction floating above the 0.60 M sucrose accounted for approx. 51% of the total CNPase activity. SDS-PAGE of membranes individually harvested from above the 0.25 and 0.60 and 0.85 M sucrose phases revealed the presence of myelin-specific proteins (P(0), P(1); and P(2)). Electron microscope examination demonstrated the presence of myelin in each membrane fraction. The results of this study show that the majority of CNPase activity is associated with "light myelin" in cat peripheral nerve.


Adherence to Newly Prescribed Diabetes Medications Among Insured Latino and White Patients With Diabetes.
Medication adherence is essential to diabetes care. Patient-physician language barriers may affect medication adherence among Latino individuals. To determine the association of patient race/ethnicity, preferred language, and physician language concordance with patient adherence to newly prescribed diabetes medications. This observational study was conducted from January 1, 2006, to December 31, 2012, at a large integrated health care delivery system with professional interpreter services. Insured patients with type 2 diabetes, including English-speaking white, English-speaking Latino, or limited English proficiency (LEP) Latino patients with newly prescribed diabetes medication. Patient race/ethnicity, preferred language, and physician self-reported Spanish-language fluency. Primary nonadherence (never dispensed), early-stage nonpersistence (dispensed only once), late-stage nonpersistence (received ≥2 dispensings, but discontinued within 24 months), and inadequate overall medication adherence (>20% time without sufficient medication supply during 24 months after initial prescription). Participants included 21 878 white patients, 5755 English-speaking Latino patients, and 3205 LEP Latino patients with a total of 46 131 prescriptions for new diabetes medications. Among LEP Latino patients, 50.2% (n = 1610) had a primary care physician reporting high Spanish fluency. For oral medications, early adherence varied substantially: 1032 LEP Latino patients (32.2%), 1565 English-speaking Latino patients (27.2%), and 4004 white patients (18.3%) were either primary nonadherent or early nonpersistent. Inadequate overall adherence was observed in 1929 LEP Latino patients (60.2%), 2975 English-speaking Latino patients (51.7%), and 8204 white patients (37.5%). For insulin, early-stage nonpersistence was 42.8% among LEP Latino patients (n = 1372), 34.4% among English-speaking Latino patients (n = 1980), and 28.5% among white patients (n = 6235). After adjustment for patient and physician characteristics, LEP Latino patients were more likely to be nonadherent to oral medications and insulin than English-speaking Latino patients (relative risks from 1.11 [95% CI, 1.06-1.15] to 1.17 [95% CI, 1.02-1.34]; P < .05) or white patients (relative risks from 1.36 [95% CI, 1.31-1.41] to 1.49 [95% CI, 1.32-1.69]; P < .05). English-speaking Latino patients were more likely to be nonadherent compared with white patients (relative risks from 1.23 [95% CI, 1.19-1.27] to 1.30 [95% CI, 1.23-1.39]; P < .05). Patient-physician language concordance was not associated with rates of nonadherence among LEP Latinos (relative risks from 0.92 [95% CI, 0.71-1.19] to 1.04 [95% CI, 0.97-1.1]; P > .28). Nonadherence to newly prescribed diabetes medications is substantially greater among Latino than white patients, even among English-speaking Latino patients. Limited English proficiency Latino patients are more likely to be nonadherent than English-speaking Latino patients independent of the Spanish-language fluency of their physicians. Interventions beyond access to interpreters or patient-physician language concordance will be required to improve medication adherence among Latino patients with diabetes.


Isolation of methicillin-resistant Staphylococcus aureus from a postoperative wound infection in a horse.
Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from a postoperative wound infection in a horse. Methicillin-resistant S aureus infections in animals have been reported. In human beings, MRSA is an important cause of hospital-acquired (nosocomial) infections. Infections caused by MRSA respond poorly to beta-lactam treatment, and resistance of MRSA to multiple antimicrobials, including aminoglycosides, macrolides, clindamycin, and tetracyclines, is common. Identification of MRSA by routine susceptibility testing may be difficult; therefore, techniques for MRSA detection should be incorporated by clinicopathology laboratories. Because the number of hospital and community-acquired MRSA infections in human beings is increasing, it seems likely that MRSA infections in animals will also become more frequent.


NO-Rich Diet for Lifestyle-Related Diseases.
Decreased nitric oxide (NO) availability due to obesity and endothelial dysfunction might be causally related to the development of lifestyle-related diseases such as insulin resistance, ischemic heart disease, and hypertension. In such situations, instead of impaired NO synthase (NOS)-dependent NO generation, the entero-salivary nitrate-nitrite-NO pathway might serve as a backup system for NO generation by transmitting NO activities in the various molecular forms including NO and protein S-nitrosothiols. Recently accumulated evidence has demonstrated that dietary intake of fruits and vegetables rich in nitrate/nitrite is an inexpensive and easily-practicable way to prevent insulin resistance and vascular endothelial dysfunction by increasing the NO availability; a NO-rich diet may also prevent other lifestyle-related diseases, including osteoporosis, chronic obstructive pulmonary disease (COPD), and cancer. This review provides an overview of our current knowledge of NO generation through the entero-salivary pathway and discusses its safety and preventive effects on lifestyle-related diseases.


Direct detection of bacterial pathogens in brain abscesses by polymerase chain reaction amplification and sequencing of partial 16s ribosomal deoxyribonucleic acid fragments.
To evaluate the feasibility of detecting bacterial pathogens directly from the clinical brain abscess specimens by polymerase chain reaction (PCR) amplification and sequencing of bacterial 16S ribosomal deoxyribonucleic acid (rDNA). A total of 14 specimens were tested by both culture and PCR amplification, targeting the full-length or a partial region of 16S rDNA. 16S rDNA is known to be conserved in bacteria. Sequencing of partial-length and full-length 16S rDNA was performed. The sequence data were compared with known sequences of 16S rDNA in the National Center for Biotechnology Information GenBank by using the Basic Local Alignment Search Tool (BLAST) algorithm. The species with the best match of similarity were regarded as the pathogenic species in the samples. We also developed a Streptococcus-specific multiplex PCR analysis for identifying members of the Streptococcus species, the most common pathogen of brain abscesses. The 10 culture-positive specimens were all PCR-positive for partial 16S rDNA, but only seven were positive for full-length 16S rDNA amplification. Bacterial DNA was not detected in the remaining four specimens with a negative culture. Species identification by phenotypes from culture was in agreement with that by sequencing results of partial-length (or full-length) 16S rDNA. The Streptococcus-specific PCR analysis could detect Streptococcus species correctly in one step. Bacterial 16S rDNA sequences provide reliable clues to the identification of unknown pathogens. PCR analysis of 16S rDNA and sequencing may identify pathogens to the species level directly from brain abscesses. This approach is rapid and is useful especially in the identification of slow-growing and fastidious organisms.


Physician and Hospital Utilization of P2Y12 Inhibitors in ST-Segment-Elevation Myocardial Infarction in the United States: A Study From the National Cardiovascular Data Registry's Research to Practice Initiative.
Background Ticagrelor and prasugrel are potent P2Y12 inhibitors with superior efficacy compared with clopidogrel among patients with ST-segment-elevation myocardial infarction (STEMI), though use in recent practice is not well described. In this retrospective study, we assessed trends, predictors, and variation in use of P2Y12 inhibitors in patients with STEMI in the United States. Methods and Results We identified 169 505 STEMI patients in the Chest Pain-Myocardial Infarction Registry from October 2013 through March 2017. We determined national utilization rates of P2Y12 inhibitors at discharge, patient predictors for each medication, and variation in use between hospitals. In a subset of 9655 Medicare patients ≥65 years old, we compared 1-year adjusted risks of death, myocardial infarction, stroke, and bleeding based on hospital quartile of potent P2Y12 inhibitor use. Rates of ticagrelor use increased from 18.0% to 44.0%, while rates of prasugrel and clopidogrel use decreased from 24.6% to 13.5% and 57.4% to 42.6%, respectively. Prior percutaneous coronary intervention was the strongest clinical predictor for use of ticagrelor (adjusted odds ratio, 1.13 [95% CI, 1.09-1.18]) and prasugrel (adjusted odds ratio, 1.27 [95% CI, 1.21-1.34]) compared with clopidogrel. Predictors of clopidogrel use included no insurance, insurance with Medicare or Medicaid, and features associated with higher bleeding risk. The median hospital usage rate for newer P2Y12 inhibitors was 51.3% (interquartile range, 35.0%-65.9%), with substantial variation between hospitals (adjusted median odds ratio, 2.92 [95% CI, 2.77-3.10]). Among patients ≥65 years old, there were no differences in adjusted 1-year risks of adverse outcomes across hospital quartiles of potent P2Y12 inhibitor use. Conclusions Almost one-half of STEMI patients by 2017 were discharged on ticagrelor while far fewer received prasugrel. Patient characteristics are associated with P2Y12 inhibitor selection, though substantial hospital variation exists. Identifying barriers to use of more potent P2Y12 inhibitors may improve patient-centered decision-making for STEMI patients.


The Effect of Peripheral Compression on Syllable Perception Measured with a Hearing Impairment Simulator.
Hearing impaired (HI) people often have difficulty understanding speech in multi-speaker or noisy environments. With HI listeners, however, it is often difficult to specify which stage, or stages, of auditory processing are responsible for the deficit. There might also be cognitive problems associated with age. In this paper, a HI simulator, based on the dynamic, compressive gammachirp (dcGC) filterbank, was used to measure the effect of a loss of compression on syllable recognition. The HI simulator can counteract the cochlear compression in normal hearing (NH) listeners and, thereby, isolate the deficit associated with a loss of compression in speech perception. Listeners were required to identify the second syllable in a three-syllable "nonsense word", and between trials, the relative level of the second syllable was varied, or the level of the entire sequence was varied. The difference between the Speech Reception Threshold (SRT) in these two conditions reveals the effect of compression on speech perception. The HI simulator adjusted a NH listener's compression to that of the "average 80-year old" with either normal compression or complete loss of compression. A reference condition was included where the HI simulator applied a simple 30-dB reduction in stimulus level. The results show that the loss of compression has its largest effect on recognition when the second syllable is attenuated relative to the first and third syllables. This is probably because the internal level of the second syllable is attenuated proportionately more when there is a loss of compression.