Cefdinir: a review of its use in the management of mild-to-moderate bacterial infections.
Cefdinir (Omnicef) is an oral third-generation cephalosporin with good in vitro activity against many pathogens commonly causative in community-acquired infections. The drug provides good coverage against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae, the most common respiratory tract pathogens. Cefdinir is stable to hydrolysis by commonly occurring plasmid-mediated beta-lactamases and retains good activity against beta-lactamase-producing strains of H. influenzae and M. catarrhalis. The drug distributes into various tissues (e.g. sinus and tonsil) and fluids (e.g. middle ear), and has a pharmacokinetic profile that allows for once- or twice-daily administration.Cefdinir, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy in the treatment of a wide range of mild-to-moderate infections of the respiratory tract and skin in adults, adolescents and paediatric patients in randomised, controlled trials. In adults and adolescents, cefdinir is an effective treatment for both lower (acute bacterial exacerbations of chronic bronchitis [ABECB], community-acquired pneumonia) and upper (acute bacterial rhinosinusitis, streptococcal pharyngitis) respiratory tract infections, and uncomplicated skin infections. Its bacteriological and clinical efficacy in patients with lower respiratory tract infections was equivalent to that of comparator agents (cefprozil [bacteriological only], loracarbef, cefuroxime axetil and cefaclor). In one trial in patients with ABECB, cefdinir produced a higher rate of clinical cure than cefprozil (95% CIs indicated nonequivalence). Cefdinir also produced good clinical and bacteriological responses equivalent to responses with amoxicillin/clavulanic acid in patients with acute bacterial rhinosinusitis. In addition, it was at least as effective as penicillin V (phenoxymethylpenicillin) in streptococcal pharyngitis/tonsillitis and as effective as cefalexin in uncomplicated skin infections. In paediatric patients aged > or =6 months, cefdinir showed similar efficacy to that of amoxicillin/clavulanic acid or cefprozil in acute otitis media, and cefalexin in uncomplicated skin infections. Cefdinir given for 5 or 10 days was at least as effective as penicillin V for 10 days in patients with streptococcal pharyngitis/tonsillitis. Cefdinir is usually well tolerated. Diarrhoea was the most common adverse event in trials in all age groups. Although the incidence of diarrhoea in cefdinir recipients was generally higher than in adults and adolescents treated with comparators, discontinuation rates due to adverse events were generally similar for cefdinir and comparator groups. In conclusion, cefdinir is a third-generation cephalosporin with a broad spectrum of antibacterial activity encompassing pathogens that are commonly causative in infections of the respiratory tract or skin and skin structure. Depending on the infection being treated, cefdinir can be administered as a convenient once- or twice-daily 5- or 10-day regimen. Clinical evidence indicates that cefdinir is an effective and generally well tolerated drug with superior taste over comparator antibacterial agents and is therefore a good option for the treatment of adults, adolescents and paediatric patients with specific mild-to-moderate respiratory tract or skin infections, particularly in areas where beta-lactamase-mediated resistance among common community-acquired pathogens is a concern.


Contemporary management of patients with T1a and T1b prostate cancer.
Incidental prostate cancer (PCa) - T1a to T1b - still represents a non-negligible clinical entity requiring good decision-making skills to correctly manage patients, most of whom may have insignificant tumours. The aim of the current review is to summarize the available evidence-based information that may be helpful in daily clinical practice. Although having major clinical implications, the current TNM staging system for incidental PCa has not been re-evaluated for 20 years. Recently, many reports questioned the accuracy of T1a-T1b classification and strengthened the fact that the decisions to offer further treatment in cases of incidental cancer should be based upon the estimated probability of clinical progression compared to the relative risk of therapy and potential benefit to survival. The use of prostate-specific antigen (PSA) levels before and after transurethral resection of the prostate (TURP) and Gleason score at diagnosis may help in estimating the need for further therapy. Active surveillance should be recommended for well differentiated incidental cancers in patients with limited life expectancy and low PSA levels after TURP or, alternatively, in patients who are uncomfortable with potential treatment-related complications. In patients with a longer life expectancy - especially for poorly differentiated tumours - radical prostatectomy should be considered. PSA levels before and after TURP increase the accuracy in estimating the need for active management. Further studies focusing on biologic and clinical markers of progression are mandatory to identify those patients who require active treatment after incidental PCa diagnosis.


Comparison between theophylline, N-acetylcysteine, and theophylline plus N-acetylcysteine for the prevention of contrast-induced nephropathy.
Few studies compared the efficacy of theophylline with N-acetylcysteine or evaluated the efficacy of combination therapy in the prevention of contrast-induced nephropathy (CIN). We compared the efficacy of theophylline, N-acetylcysteine, and the combination of these agents in the prevention of CIN. This randomized controlled trial was conducted on 96 patients referring consecutively to the Shahid Chamran University Hospital in Isfahan, Iran, for elective coronary angiography (with our without angioplasty). Patients with at least moderate risk for CIN were included and were randomized to receive theophylline (200 mg), N-acetylcysteine (600 mg), or theophylline + N-acetylcysteine, twice a day, from 24 h before to 48 h after administration of the contrast material. A non-ionic, low-osmolar contrast material was used. Serum creatinine was measured before and 48 h after contrast material injection. Serum creatinine was increased by 6.83 ± 15.32% with theophylline, 13.09 ± 14.63% with N-acetylcysteine, and 5.45 ±1 3.96% with theophylline + N-acetylcysteine after contrast material injection (between group P = 0.072). Controlling for Mehran risk score, baseline serum creatinine, and contrast volume, the change in serum creatinine level was lower with theophylline compared with N-acetylcysteine (F = 4.79, P = 0.033), and with theophylline + N-acetylcysteine compared with N-acetylcysteine (F = 5.78, P = 0.020). CIN (increase in creatinine of ≥ 0.5 mg/dl or ≥ 25% from the baseline) was occurred in 20%, 21.9%, and 7.1% of patients in the theophylline, N-acetylcysteine, and theophylline + N-acetylcysteine groups, respectively (P = 0.260). Theophylline is superior to N-acetylcysteine in preventing contrast-induced renal dysfunction, but the combination with N-acetylcysteine is not superior to theophylline alone in this regard. Further trials with larger sample of patients are warranted.


Measuring Antiviral Capacity of T Cell Responses to Adenovirus.
Adenoviruses are a major cause of infectious mortality in children following allogeneic hematopoietic stem cell transplantation, with adoptive transfer of adenovirus-specific T cells being an effective therapeutic approach. We have previously shown that T cells specific for the peptide epitope LTDLGQNLLY were protective. In this study, we aimed to establish a viral dissemination assay to measure the antiviral capacity of T cells specific for this and other peptide epitopes in an infectious setting. We used replication-competent adenovirus 11 (Ad11pGFP) and adenovirus 5 containing adenovirus 35 fiber (Ad5F35GFP) viruses and T cells specific for HLA-A*01-restricted LTDLGQNLLY, HLA-B*07-restricted KPYSGTAYNAL, and HLA-A*02-restricted LLDQLIEEV peptide epitopes. T cells in PBMC from healthy donors were expanded with peptide and IL-2 or treated with IL-2 alone to serve as nonstimulated control cells, and then these expanded or nonstimulated CD8+ cells were purified and cocultured with autologous monocytes infected with adenovirus at low multiplicity of infection. After 3 d, the number of infected GFP+ monocytes and, hence, viral dissemination was quantified by flow cytometry. T cells expanded with LTDLGQNLLY peptide from multiple HLA-A*01+ donors prevented adenovirus dissemination, and nonstimulated T cells did not prevent dissemination, thus, indicating that LTDLGQNLLY-specific T cells have high antiviral capacity. Similarly, expanded KPYSGTAYNAL- and LLDQLIEEV-specific T cells could prevent viral dissemination. However, the frequency of expanded T cells specific for these last two epitopes was variable between donors with consequent variable prevention of adenoviral dissemination. Taken together, we demonstrate that T cells specific for three peptide epitopes, from both structural and nonstructural proteins, can prevent adenoviral dissemination and provide a novel method to measure the antiviral capacity of adenovirus-specific T cell responses.


[Fulminant meningococcemia with intracranial hypertension. External lumbar drainage of cerebrospinal fluid].
An 18-year old girl developed acute fulminating meningococcaemia with meningitis, coma, shock, coagulation disorders and extensive purpura. Measurement of intracranial pressure showed severe intracranial hypertension. After medical treatment of shock and intracranial hypertension had failed, external drainage of the cerebrospinal fluid was performed in the lumbar region, using a 16 G silicone catheter. This controlled the intracranial hypertension; also the state of shock regressed and the patient became fully conscious. The lumbar drainage was maintained for 12 days during which 3180 ml of blood-stained cerebrospinal fluid were evacuated. The fluid was sterilized by antibiotics as early as the 1st day of the disease, but it remained positive for bacterial antigen up to the 9th day. Cure was obtained without neurological sequelae, thanks to the lumber drainage which controlled intracranial hypertension and removed large amounts of microbial toxins.


[Changes of ultrastructure of the capillary endotheliocytes of ischemized and nonaffected muscular tissue after transplantation of human hemopoietic stem cells of fetal liver in experiment in vivo].
In experiment was investigated ultrastructure of the capillaries endothelial cells and histological peculiarities of muscular tissue on various stages after transplantation of hemopoietic stem cells of fetal liver (HSCFL). There was proved, that in ischemic environment HSCFL stimulate processes of angiogenesis, and in the case of transplantation into intact muscular tissue they are differentiating into the tissue macrophages, not interfering with muscular tissue structure.


Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens.
The mTOR pathway is hyperactivated through oncogenic transformation in many human malignancies. Ridaforolimus (AP23573; MK-8669) is a novel rapamycin analogue that selectively targets mTOR and is currently under clinical evaluation. In this study, we investigated the mechanistic basis for the antitumor activity of ridaforolimus in a range of human tumor types, exploring potential markers of response, and determining optimal dosing regimens to guide clinical studies. Administration of ridaforolimus to tumor cells in vitro elicited dose-dependent inhibition of mTOR activity with concomitant effects on cell growth and division. We showed that ridaforolimus exhibits a predominantly cytostatic mode of action, consistent with the findings for other mTOR inhibitors. Potent inhibitory effects on vascular endothelial growth factor secretion, endothelial cell growth, and glucose metabolism were also observed. Although PTEN and/or phosphorylated AKT status have been proposed as potential mTOR pathway biomarkers, neither was predictive for ridaforolimus responsiveness in the heterogeneous panel of cancer cell lines examined. In mouse models, robust antitumor activity was observed in human tumor xenografts using a series of intermittent dosing schedules, consistent with pharmacodynamic observations of mTOR pathway inhibition for at least 72 hours following dosing. Parallel skin-graft rejection studies established that intermittent dosing schedules lack the immunosuppressive effects seen with daily dosing. Overall these findings show the broad inhibitory effects of ridaforolimus on cell growth, division, metabolism, and angiogenesis, and support the use of intermittent dosing as a means to optimize antitumor activity while minimizing systemic effects.


Sputum neutrophil elastase associates with microbiota and Pseudomonas aeruginosa in bronchiectasis.
Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics. An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected. Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ -0.37, p<0.00001) and Pielou's evenness (ρ -0.36, p<0.00001) and richness (ρ -0.33, p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL-1 (median 3.82, interquartile range 2.20-4.96) versus neutrophil elastase <20 µg·mL-1 (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR. High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection.


Chronic electromyograms in treadmill running SOD1 mice reveal early changes in muscle activation.
The present study demonstrates that electromyograms (EMGs) obtained during locomotor activity in mice were effective for identification of early physiological markers of amyotrophic lateral sclerosis (ALS). These measures could be used to evaluate therapeutic intervention strategies in animal models of ALS. Several parameters of locomotor activity were shifted early in the disease time course in SOD1G93A mice, especially when the treadmill was inclined, including intermuscular phase, burst skew and amplitude of the locomotor bursts. The results of the present study indicate that early compensatory changes may be taking place within the neural network controlling locomotor activity, including spinal interneurons. Locomotor EMGs could have potential use as a clinical diagnostic tool. To improve our understanding of early disease mechanisms and to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, we measured electromyogram (EMG) activity in hind limb muscles of SOD1G93A mice. By contrast to clinical diagnostic measures using EMGs, which are performed on quiescent patients, we monitored activity during treadmill running aiming to detect presymptomatic changes in motor patterning. Chronic EMG electrodes were implanted into vastus lateralis, biceps femoris posterior, lateral gastrocnemius and tibialis anterior in mice from postnatal day 55 to 100 and the results obtained were assessed using linear mixed models. We evaluated differences in parameters related to EMG amplitude (peak and area) and timing (phase and skew, a measure of burst shape) when animals ran on level and inclined treadmills. There were significant changes in both the timing of activity and the amplitude of EMG bursts in SOD1G93A mice. Significant differences between wild-type and SOD1G93A mice were mainly observed when animals locomoted on inclined treadmills. All muscles had significant effects of mutation that were independent of age. These novel results indicate (i) locomotor EMG activity might be an early measure of disease onset; (ii) alterations in locomotor patterning may reflect changes in neuronal drive and compensation at the network level including altered activity of spinal interneurons; and (iii) the increased power output necessary on an inclined treadmill was important in revealing altered activity in SOD1G93A mice.


Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure, leptin and thyrotropin levels in obese non-morbid premenopausal women.
Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0 ± 2.8 kg/m(2)) women (age 36.7 ± 7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy-Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580 ± 22 vs. 1,739 ± 35 kcal/day, P < 0.001) and higher leptin to fat mass ratio (1.33 ± 0.05 vs. 1.13 ± 0.08 ng/ml kg, P < 0.05) and thyrotropin levels (1.93 ± 0.10 vs. 1.53 ± 0.16 μU/ml, P < 0.05) regardless of age and body mass index. We found no significant influence of the MC4R rs17782313 on energy metabolism or biochemical variables. Our findings confirm that the A allele of the FTO rs9939609 is associated with lower REE and increased plasma leptin levels. We also found an association between the FTO rs9939609 and thyrotropin, suggesting the possible influence of FTO in the hypothalamic-pituitary-thyroid axis as a potential mechanism of the increased adiposity.


Using evidence to decision frameworks led to guidelines of better quality and more credible and transparent recommendations.
To determine whether the use of Evidence to Decision (EtD) frameworks is associated to higher quality of both guidelines and individual recommendations. We identified guidelines recently published by international organizations that have methodological guidance documents for their development. Pairs of researchers independently extracted information on the use of these frameworks, appraised the quality of the guidelines using the Appraisal of Guidelines, Research and Evaluation II Instrument (AGREE-II), and assessed the clinical credibility and implementability of the recommendations with the Appraisal of Guidelines for REsearch & Evaluation Recommendations Excellence (AGREE-REX) tool. We conducted both descriptive and inferential analyses. We included 66 guidelines from 17 different countries, published in the last 5 years. Thirty guidelines (45%) used an EtD framework to formulate their recommendations. Compared to those that did not use a framework, those using an EtD framework scored higher in all domains of both AGREE-II and AGREE-REX (P < 0.05). Quality scores did not differ between the use of the The Grading of Recommendations Assessment, Development and Evaluation-EtD framework (17 guidelines) or another EtD framework (13 guidelines) (P > 0.05). The use of EtD frameworks is associated with guidelines of better quality, and more credible and transparent recommendations. Endorsement of EtD frameworks by guideline developing organizations will likely increase the quality of their guidelines.


Basic Promotors Impact Thermodynamics and Catalyst Speciation in Homogeneous Carbonyl Hydrogenation.
Homogeneously catalyzed reactions often make use of additives and promotors that affect reactivity patterns and improve catalytic performance. While the role of reaction promotors is often discussed in view of their chemical reactivity, we demonstrate that they can be involved in catalysis indirectly. In particular, we demonstrate that promotors can adjust the thermodynamics of key transformations in homogeneous hydrogenation catalysis and enable reactions that would be unfavorable otherwise. We identified this phenomenon in a set of well-established and new Mn pincer catalysts that suffer from persistent product inhibition in ester hydrogenation. Although alkoxide base additives do not directly participate in inhibitory transformations, they can affect the equilibrium constants of these processes. Experimentally, we confirm that by varying the base promotor concentration one can control catalyst speciation and inflict substantial changes to the standard free energies of the key steps in the catalytic cycle. Despite the fact that the latter are universally assumed to be constant, we demonstrate that reaction thermodynamics and catalyst state are subject to external control. These results suggest that reaction promotors can be viewed as an integral component of the reaction medium, on its own capable of improving the catalytic performance and reshaping the seemingly rigid thermodynamic landscape of the catalytic transformation.


Metabolic and mitotic changes associated with the fetal alcohol syndrome.
In the USA, fetal alcohol syndrome (FAS) is the leading known cause of mental retardation. FAS is estimated to affect 4000 infants yearly in the USA with an additional 7000 children suffering various forms of fetal alcohol effects in the absence of the full syndrome. A comparable incidence would be expected in other industrialized countries, but essentially no data are available from either developing or third world countries. An understanding of the biochemical causes of FAS has been slow to develop, but progress has been made toward a molecular causation theory of FAS. This paper summarizes much of the current work as to the effects of fetal ethanol exposure on mitotic and metabolic parameters as well as ethanol's effect on the cellular signalling pathways thought to regulate these processes. Based upon these studies, it is apparent that exposure of embryonic tissue to ethanol results in decreased growth and that alcohol adversely affects a multitude of cellular functions critical for the growth of the developing organism, including inhibition of protein and DNA synthesis. In addition, ethanol alters the uptake of critical nutrients such as glucose and amino acids and causes changes in several kinase-mediated signal transduction pathways that regulate these biochemical processes.


Presepsin as a biomarker in perioperative medicine.
Presepsin is the soluble fragment of CD14, a multifunctional glycoprotein expressed on the surface of innate immune cells. In healthy individuals, presepsin is present in very low concentrations with reference values ranging from 60 to 382 pg/mL. Several studies have shown that presepsin is a valuable biomarker for sepsis diagnosis in adults. Only lately, presepsin has been evaluated for prediction and early detection of neonatal sepsis and septic shock. Elevated plasma presepsin concentration has also been reported in patients undergoing cardiac and non-cardiac surgery and it has further been evaluated as a potential independent predictor of perioperative cardiovascular complications and mortality. Combined cardiac and inflammatory biomarker evaluation may offer additive predictive information, but further investigations in large populations are required to determine presepsin diagnostic and prognostic value, in order to personalize therapy and reduce surgical patients' morbidity and mortality.


Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes.
The major histocompatibility complex (MHC) is present at a single chromosomal locus of all jawed vertebrate analyzed so far, from sharks to mammals, except for teleosts whose orthologs of the mammalian MHC-encoded genes are dispersed at several chromosomal loci. Even in teleosts, several class IA genes and those genes directly involved in class I antigen presentation preserve their linkage, defining the teleost MHC class I region. We determined the complete nucleotide sequence of the MHC class I region of the inbred HNI strain of medaka, Oryzias latipes (northern Japan population-derived), from four overlapping bacterial artificial chromosome (BAC) clones spanning 540,982 bp, and compared it with the published sequence of the corresponding region of the inbred Hd-rR strain of medaka (425,935 bp, southern Japan population-derived) as the first extensive study of intraspecies polymorphisms of the ectotherm MHC regions. A segment of about 100 kb in the middle of the compared sequences encompassing two class Ia genes and two immunoproteasome subunit genes, PSMB8 and PSMB10, was so divergent between these two inbred strains that a reliable sequence alignment could not be made. The rest of the compared region (about 320 kb) showed a fair correspondence, and an approximately 96% nucleotide identity was observed upon gap-free segmental alignment. These results indicate that the medaka MHC class I region contains an approximately 100-kb polymorphic core, which is most probably evolving adaptively by accumulation of point mutations and extensive genetic rearrangements such as insertions, deletions, and duplications.


Clenbuterol increases the expression of myogenin but not myoD in immobilized rat muscles.
Immobilization of one hindlimb of young rats in plantar flexion for 3 days led to changes in the plantaris muscles. These comprised a loss of muscle mass and a reduction in protein and RNA content, but no change in the transcript levels of the myogenic regulatory factors myogenin and myoD. Dietary administration of the beta-adrenoceptor agonist clenbuterol (2 mg/kg diet), which has been shown to ameliorate muscle wasting in a wide range of atrophic conditions, also limited muscle wasting in terms of weight, protein, and RNA in the immobilized plantaris muscles. In addition, drug treatment in immobilized plantaris muscles was associated with a marked increase in the steady-state levels of mRNA for myogenin (approximately 360% increase over control) but not myoD. These data provide the first evidence for independent changes in these two myogenic regulatory factors in immobilized muscle and suggest that the action of clenbuterol on these factors may depend on the mechanistic basis for the atrophic response.


Endogenous interleukin-4, but not interleukin-10, is involved in suppression of host resistance against Listeria monocytogenes infection in interferon-depleted mice.
The production and roles of endogenous interleukin-4 (IL-4) and IL-10 in a sublethal infection with Listeria monocytogenes were studies in normal mice and anti-gamma interferon (IFN-gamma) monoclonal antibody (MAb)-pretreated mice. In normal mice, the expression of mRNAs for IL-4 and IL-10, which was amplified by reverse transcription-PCR, was induced in the spleens and livers either early or late in infection, although the serum IL-4 and IL-10 were not detectable by enzyme-linked immunosorbent assays. In vivo administration of anti-IL-4 MAb showed no effect on antilisterial resistance, whereas anti-IL-10 MAb partially diminished the defense. In anti-IFN-gamma MAb-pretreated mice, a delay in the bacterial elimination from the spleens and livers was observed and high titers of serum IL-4 and IL-10 were induced late in infection. Production of endogenous IL-4 and IL-10 was suppressed in both CD4+ cell-and CD8+ cell depleted mice. The suppression of antilisterial resistance in anti-IFN-gamma MAb-pretreated mice was canceled when anti-IL-4 MAb was injected late in infection, whereas anti-IL-10 MAb showed no effect. These results suggest that the host immune responses were polarized into the T-helper 2 phenotype in anti-IFN-gamma MAb-pretreated mice and that inhibition of host resistance against L. monocytogenes by depletion of IFN-gamma might be attributable to IL-4 produced by T cells polarized into the T-helper 2 phenotype as well as the inhibition of the IFN-gamma effects.


Four-year analysis of cataract surgery rates in Shanghai, China: a retrospective cross-sectional study.
The cataract surgery rate (CSR) is a critical index used to show that cataract blindness is being eliminated. It is considered to be tightly connected to social economic development; however, it is still extremely low in developing countries such as China. Although Shanghai is the most economically developed city in China, its CSR and the obstacles for increasing its CSR have not been previously evaluated. A retrospective cross-sectional study was conducted. By analyzing the data in the "Shanghai Cataract Operations Database" from 2006 to 2009, the CSR in Shanghai was calculated. The numbers of cataract surgeries between urban and suburban districts as well as among various medical institutions were compared. The CSR in Shanghai increased from 1741 in 2006 to 2210 in 2009, reflecting a 26.94% improvement. Phacoemulsification was the most frequent surgical choice for cataract removal, accounting for 94.93% of total cataract surgeries by 2009. In addition, by 2009, the CSR in urban districts had reached 5468, but only 532 in the suburbs. During 2009, cataract surgery records in 68 district hospitals, 23 medical centers, and 6 private hospitals comprised 32.05%, 52.33%, and 15.62%, respectively, of the total. There was a nearly 3.3-fold increase in the number of surgeries performed in private hospitals in the past four years. Furthermore, the average number of cataract surgeries per doctor that took place in private hospitals per year reached 207, which exceeded the average of 145 that took place in medical centers. Until 2009, the CSR in Shanghai remained below the rates of social development and fell short of targets suggested by the World Health Organization (WHO). Furthermore, increasing the CSR in the suburbs as well as in district hospitals is an important issue that needs to be addressed.


Real-World Treatment Patterns of Multiple-Inhaler Triple Therapy Among Patients with Chronic Obstructive Pulmonary Disease in UK General Practice.
Until recently, triple therapy for chronic obstructive pulmonary disease (COPD) has only been available through treatment with multiple inhalers. Evidence on real-world use of multiple-inhaler triple therapy (MITT), including duration of use and treatment patterns, is limited. A retrospective, observational study of electronic health records and hospital episodes in patients with COPD initiating MITT between 2013 and 2015 in the UK was performed. This study described patients initiating, treatment persistence and discontinuation, and prior and subsequent COPD treatments. Eligible patients (N=3825) had a mean age of 69.5 years; most were former or current smokers (95%). The majority (86%) initiated MITT with two inhalers and 14% initiated with three inhalers. Mean duration of use was 5.1 (standard deviation: 4.6) months; 24% of patients persisted for 12 months. Patients who had significantly poorer lung function at baseline (12 months prior to initiating MITT) and had experienced significantly more moderate-to-severe acute exacerbation of COPD (AECOPD) and hospitalizations during the baseline period were more likely to persist for 12 months, compared with those who discontinued within 12 months. Most patients stepped down to an inhaled corticosteroid/long-acting β2-agonist combination (ICS/LABA; 48%) or a long-acting muscarinic antagonist (LAMA; 45%) after discontinuing MITT. Initiation of MITT occurred in patients with clinically relevant symptoms and a history of AECOPD. Persistence varied and was most likely linked to disease severity, although more research is required to fully understand why patients discontinue MITT, the subsequent clinical consequences of therapy discontinuation, and the potential impact of newly available single-inhaler triple therapies.


Soybean basic 7S globulin: subunit heterogeneity and molecular evolution.
Basic 7S globulin, a cysteine-rich protein from soybean seeds, consists of subunits containing 27 kD and 16 kD chains linked by disulfide bonding. Three differently sized subunits of the basic 7S globulin were detected and partially separated by SP Sepharose chromatography. The basic 7S globulin was characterized as a member of a superfamily of structurally related but functionally distinct proteins descended from a specific group of plant aspartic proteinases.


Training improves the interobserver agreement of the expert positron emission tomography review panel in primary mediastinal B-cell lymphoma: interim analysis in the ongoing International Extranodal Lymphoma Study Group-37 study.
The International Extranodal Lymphoma Study Group (IELSG)-37 is a prospective randomized trial assessing the role of consolidation mediastinal radiotherapy after immunochemotherapy to patients with newly diagnosed primary mediastinal large B-cell lymphoma (PMBCL). It is a positron emission tomography (PET) response-guided study where patients obtaining a complete metabolic response on an end-of-therapy PET-computed tomography (CT) scan evaluated by a central review are randomized to receive radiotherapy or no further treatment. The aims of this study were to measure agreement between reviewers reporting PET-CT scans for this trial and to determine the effect of training upon concordance rates. The review panel comprised 6 experienced nuclear physicians who read PET-CT scans using the 5-point Deauville scale. Interobserver agreement (IOA) was measured at 4 time points: after a blinded review of a "training set" of 20 patients with PMBCL from the previous IELSG-26 study (phase 1); after the first 10 clinical cases enrolled in the IELSG-37 (phase 2); and after 2 further groups of 50 (phase 3) and 40 clinical cases (phase 4). After feedback from the training set and the first 10 cases, a meeting was held to discuss interpretation, and a detailed set of instructions for the review procedure was agreed and acted upon. Between 2012 and 2014, the first 100 patients were reviewed. Using Deauville score 3 as the cutoff for a complete metabolic response, the overall IOA among the reviewers was good (Krippendorff α = 0.72.) The binary concordance between pairs of reviewers (Cohen κ) ranged from 0.60 to 0.78. The IOA, initially moderate, improved progressively from phase 1 to 4 (Krippendorff α from 0.53 to 0.81; Cohen κ from 0.35-0.72 to 0.77-0.87). Our experience indicates that the agreement among "expert" nuclear physicians reporting PMBCL, even using standardized criteria, was only moderate when the study began. However, agreement improved using a harmonization process, which included a training exercise with discussion of points leading to disagreement and compiling practical rules to sit alongside commonly adopted interpretation criteria.


Area postrema lesion attenuates the long-term hypotensive effects of losartan in salt-replete rats.
We reported that the AT1 receptor antagonist losartan decreases arterial pressure in sodium-replete rats and that this response is attenuated in area postrema-lesioned (APx) rats (J. P. Collister, B. J. Hornfeldt, and J. W. Osborn. Hypertension 27: 598-606, 1996). In that study, food intake for the 3-wk period after sham lesion was restricted to that observed in APx rats. Food-restricted sham rats had lower arterial pressures and attenuated responses to losartan compared with control rats fed ad libitum. The present study examined whether these differences persisted months, rather than weeks after APx or sham lesions. Losartan was administered for 10 days to APx and two groups of sham rats 3 mo after APx or sham surgery. The first sham group was food restricted (SFR) for 3 wk after surgery, whereas the second sham group was allowed ad libitum (SAL) access to food. By day 8 of losartan administration, both sham groups demonstrated a marked hypotension (SFR: -38 +/- 4; SAL: -33 +/- 4 mmHg). This response was attenuated (P < 0.05) on the same day in APx rats (-17 +/- 3 mmHg). This trend continued throughout days 9 and 10. Because both sham groups responded similarly to losartan (yet significantly different from APx rats), these results demonstrate that transient decreases in food intake do not affect the response to losartan if rats are allowed an adequate recovery period. We conclude that the area postrema mediates part of the long-term hypotensive effects of AT1 receptor blockade in the conscious rat.


L-serine: Neurological Implications and Therapeutic Potential.
L-serine is a non-essential amino acid that plays a vital role in protein synthesis, cell proliferation, development, and sphingolipid formation in the central nervous system. It exerts its effects through the activation of glycine receptors and upregulation of PPAR-γ, resulting in neurotransmitter synthesis, neuroprotection, and anti-inflammatory effects. L-serine shows potential as a protective agent in various neurological diseases and neurodegenerative disorders. Deficiency of L-serine and its downstream products has been linked to severe neurological deficits. Despite its crucial role, there is limited understanding of its mechanistic production and impact on glial and neuronal cells. Most of the focus has been on D-serine, the downstream product of L-serine, which has been implicated in a wide range of neurological diseases. However, L-serine is approved by FDA for supplemental use, while D-serine is not. Hence, it is imperative that we investigate the wider effects of L-serine, particularly in relation to the pathogenesis of several neurological deficits that, in turn, lead to diseases. This review aims to explore current knowledge surrounding L-serine and its potential as a treatment for various neurological diseases and neurodegenerative disorders.


Microbiological laboratory results from Haiti: June-October 1995.
From June to October 1995, the U.S. Army's 86th Combat Support Hospital was deployed in Haiti in support of the United Nations peacekeeping mission. The hospital's mission was to provide comprehensive health care to United Nations military and civilian personnel in Haiti. The hospital's laboratory, with microbiological and parasitological capability, was a critical asset in light of the infectious disease threats in Haiti. A total of 356 microbiological (5.4%) and 887 parasitological (13.4%) tests were performed, out of a total of 6628 laboratory tests. One finding was the discovery of antibiotic-resistant urinary isolates of Escherichia coli. These were from community-acquired infections and included strains resistant to ampicillin (6/15), trimethoprim+sulfamethoxazole (6/15), and ciprofloxacin (2/15). Ampicillin (8/15) and trimethoprim+sulfamethoxazole (3/15) resistance was also noted in Shigella spp. However, no chloroquine-resistant strains of malaria were encountered. Dengue virus, also mosquito borne, was a major pathogen. Antimicrobial-resistant nosocomial pathogens were also encountered. Deployed laboratories should be able to determine antimicrobial susceptibility and perform microbial identification to guide clinical management, conduct medical surveillance, and detect emerging resistance.


Efficacy of physiotherapy for urinary incontinence following prostate cancer surgery.
The study enrolled 81 with urinary incontinence following radical prostate-only prostatectomy for prostatic carcinoma. The patients were divided into two groups. The patients in Group I were additionally subdivided into two subgroups with respect to the physiotherapeutic method used. The patients of subgroup IA received a rehabilitation program consisting of three parts. The patients of subgroup IB rehabilitation program consist of two parts. Group II, a control group, had reported for therapy for persistent urinary incontinence following radical prostatectomy but had not entered therapy for personal reasons. For estimating the level of incontinence, a 1-hour and 24-hour urinary pad tests, the miction diary, and incontinence questionnaire were used, and for recording the measurements of pelvic floor muscles tension, the sEMG (surface electromyography) was applied. The therapy duration depended on the level of incontinence and it continued for not longer than 12 months. Superior continence outcomes were obtained in Group I versus Group II and the difference was statistically significant. The odds ratio for regaining continence was greater in the rehabilitated Group I and smaller in the group II without the rehabilitation. A comparison of continence outcomes revealed a statistically significant difference between Subgroups IA versus IB. The physiotherapeutic procedures applied on patients with urine incontinence after prostatectomy, for most of them, proved to be an effective way of acting, which is supported by the obtained results.


Inferring actual treatment pathways from patient records.
Treatment pathways are step-by-step plans outlining the recommended medical care for specific diseases; they get revised when different treatments are found to improve patient outcomes. Examining health records is an important part of this revision process, but inferring patients' actual treatments from health data is challenging due to complex event-coding schemes and the absence of pathway-related annotations. The objective of this study is to develop a method for inferring actual treatment steps for a particular patient group from administrative health records - a common form of tabular healthcare data - and address several technique- and methodology-based gaps in treatment pathway-inference research. We introduce Defrag, a method for examining health records to infer the real-world treatment steps for a particular patient group. Defrag learns the semantic and temporal meaning of healthcare event sequences, allowing it to reliably infer treatment steps from complex healthcare data. To our knowledge, Defrag is the first pathway-inference method to utilise a neural network (NN), an approach made possible by a novel, self-supervised learning objective. We also developed a testing and validation framework for pathway inference, which we use to characterise and evaluate Defrag's pathway inference ability, establish benchmarks, and compare against baselines. We demonstrate Defrag's effectiveness by identifying best-practice pathway fragments for breast cancer, lung cancer, and melanoma in public healthcare records. Additionally, we use synthetic data experiments to demonstrate the characteristics of the Defrag inference method, and to compare Defrag to several baselines, where it significantly outperforms non-NN-based methods. Defrag offers an innovative and effective approach for inferring treatment pathways from complex health data. Defrag significantly outperforms several existing pathway-inference methods, but computationally-derived treatment pathways are still difficult to compare against clinical guidelines. Furthermore, the open-source code for Defrag and the testing framework are provided to encourage further research in this area.


Metabolic cooperation between mouse mammary tumor subpopulations in three-dimensional collagen gel cultures.
A series of subpopulation lines derived from a single mouse mammary tumor were tested for their ability to interact with each other in metabolic cooperation assays in three-dimensional collagen gel cultures. Inhibition of growth in the presence of selective drug (6-thioguanine or 2-fluoroadenine) of two 6-thioguanine-resistant cell lines, 66cl4 and 44FTO, as well as a 2-fluoroadenine-resistant line, 168FAR, occurred in the presence of other sensitive cells, demonstrating the transfer of drug sensitivity to drug-resistant cells. Transfer of drug resistance was shown by using selective medium containing hypoxanthine, aminopterin, and thymidine plus ouabain in which mutual metabolic cooperation between line 66cl4 (also ouabain resistant) and "wild-type" lines is required for growth. Effective communication leading to the transfer of drug resistance and ultimate survival of both cell types occurred in mixtures containing as little as 10% of either cell type. The requirement for mutual metabolic cooperation in hypoxanthine, aminopterin, and thymidine plus ouabain medium prevented line 66 from overgrowing line 66cl4 to the extent that it did in control medium. The ranked abilities of lines 66, 410.4, and 168 to promote growth when mixed with line 66cl4 in collagen cultures in hypoxanthine, aminopterin, and thymidine plus ouabain medium were correlated with the ranked cell densities required for these same cell lines to inhibit growth of line 66cl4 by metabolic cooperation in the presence of 6-thioguanine in monolayer cultures. These ranked abilities may be related to the effectiveness with which each of these cell lines is able to form communicating junctions with line 66cl4.


Fully inkjet-printed two-dimensional material field-effect heterojunctions for wearable and textile electronics.
Fully printed wearable electronics based on two-dimensional (2D) material heterojunction structures also known as heterostructures, such as field-effect transistors, require robust and reproducible printed multi-layer stacks consisting of active channel, dielectric and conductive contact layers. Solution processing of graphite and other layered materials provides low-cost inks enabling printed electronic devices, for example by inkjet printing. However, the limited quality of the 2D-material inks, the complexity of the layered arrangement, and the lack of a dielectric 2D-material ink able to operate at room temperature, under strain and after several washing cycles has impeded the fabrication of electronic devices on textile with fully printed 2D heterostructures. Here we demonstrate fully inkjet-printed 2D-material active heterostructures with graphene and hexagonal-boron nitride (h-BN) inks, and use them to fabricate all inkjet-printed flexible and washable field-effect transistors on textile, reaching a field-effect mobility of ~91 cm2 V-1 s-1, at low voltage (<5 V). This enables fully inkjet-printed electronic circuits, such as reprogrammable volatile memory cells, complementary inverters and OR logic gates.


Pharmacological management of osteoporosis in nursing home populations: a systematic review.
Nursing home (NH) residents fall 11 times as frequently as their age-matched community-dwelling counterparts. The benefits of fall prevention strategies and hip protectors in terms of fracture risk in this setting are unclear. Moreover, there is no consensus on the efficacy of osteoporosis medication in NH residents. A systematic review was conducted to evaluate the efficacy of medications for osteoporosis in this population and to examine utilization studies in the NH setting to define prescribing practices. Electronic searches of MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were supplemented with a hand search of bibliographies. All English-language studies published between January 1, 1974, and December 31, 2006, that studied osteoporosis pharmacotherapy in the NH environment were obtained, and studies of medication benefits and utilization patterns were identified. No restrictions were placed on study method. Studies required inclusion of NH patients and extractable data with bone mineral density (BMD) or fracture outcomes. Forty full-text articles were retrieved, of which 15 studies met selection criteria. In the nine studies examining medication effects, calcium (1,200 mg) and vitamin D (800 IU) supplementation were shown to reduce fracture risk and improve BMD. One study supported the role of alendronate, but none documented the utility of raloxifene, calcitonin, or teriparatide in NH residents. All six medication utilization studies reported infrequent use of osteoporosis medications (9-25%). Prescribing for elderly NH patients is difficult, considering the risk:benefit ratio and issues of longevity, but these medications may be underused in the NH environment.


[Difficulties and Countermeasures for Ortho Process Optimization in DR System].
Making an Ortho image is an important method to diagnose spinal and leg lesions in clinic. As the whole process requires multiple exposures in different positions, and it is very complicated and time consuming, it leads to low efficiency and it's hard to obtain ideal stitching result from image quality. The optimization of the workflow can not only reduce the workload of the operator, improve the work efficiency, but also improve the comfort of the patient in the process, finally to ensure the quality of the stitching image. This paper firstly introduces the background and workflow of making an Ortho image. Then, each optimization solutions are elaborated, including the encountered difficulties and the countermeasures. It provides a detailed reference about how to realize the Ortho function in DR system.


Biochemical characterization of fluorescent-labeled recombinant human alpha-L-iduronidase in vitro.
In vivo tracking of the delivery of therapeutic proteins is a useful tool for preclinical studies. However, many labels are too large to use without disrupting the normal uptake, function, or other properties of the protein. Low-molecular-weight fluorescent labels allow in vivo and ex vivo tracking of the distribution of therapeutic proteins, and should not alter the protein's characteristics. We tested the in vitro properties of fluorescent-labeled recombinant human alpha-l-iduronidase (rhIDU, the enzyme deficient in Hurler syndrome) and compared labeled to unlabeled proteins. Labeled rhIDU retained full enzymatic activity and showed similar kinetics to nonlabeled rhIDU. Uptake of labeled rhIDU into human Hurler fibroblasts, measured by activity assay, was equivalent to unlabeled rhIDU enzyme and showed an uptake constant of 0.72 nM. Labeled rhIDU was also able to enter cells via the mannose 6-phospate receptor pathway and reduce glycosaminoglycan storage in Hurler fibroblasts. Subcellular localization was verified within lysosomes by confocal microscopy. These findings suggest that fluorescent labeling does not significantly interfere with enzymatic activity, stability, or uptake, and validates this method as a way to track exogenously administered enzyme.


[The application of target-based tissue-agnostic therapy in the treatment of lung cancer].
More than 6 million mutations of more than 600 cancer genes can occur in over 200 tumor types according to the COSMIC (Catalogue of Somatic Mutations in Cancer) database. The theoretical combination of all "driver" alterations and tumor types adds up to an enormous number. Therefore, there is a legitimate need to use the same targeted therapy in the presence of its target and mechanism of action in multiple tumor types. The first tissue-agnostic drugs that are registered solely based on molecular biomarkers are the NTRK inhibitors (larotrectinib and entrectinib) and the PD-1 inhibitor pembrolizumab in microsatellite instable (MSI) and tumor mutation burden (TMB) high tumors. These targets are also present in lung cancer, and we have clinical proof of the activity of treatments. In addition, the molecular targets of many targeted therapies registered in other tumor types occur in lung cancer for target-based tissue-agnostic therapy planning in lung cancer.


Using PEACE to target helmet legislation involving nonmotorized wheeled sports in Canada.
Current Canadian helmet bylaws focus mainly on bicycle helmet use. In this way, law makers are ignoring head injuries associated with other wheeled sports. Cycling, in-line skating, skateboarding, and scootering can all cause serious injury to participants if proper protective gear is not worn. Legislation has been shown to work in promoting helmet use and decreasing injuries. Nurses, using theory and research to guide practice, can be key players in advocating for healthy public policies and amendments to provincial legislation. Nurses have the opportunity to play an active leadership role that can be guided by PEACE, a philosophy that encompasses praxis, empowerment, awareness, cooperation, and evolvement.


Noisy Quantum Metrology Enhanced by Continuous Nondemolition Measurement.
We show that continuous quantum nondemolition (QND) measurement of an atomic ensemble is able to improve the precision of frequency estimation even in the presence of independent dephasing acting on each atom. We numerically simulate the dynamics of an ensemble with up to N=150 atoms initially prepared in a (classical) spin coherent state, and we show that, thanks to the spin squeezing dynamically generated by the measurement, the information obtainable from the continuous photocurrent scales superclassically with respect to the number of atoms N. We provide evidence that such superclassical scaling holds for different values of dephasing and monitoring efficiency. We moreover calculate the extra information obtainable via a final strong measurement on the conditional states generated during the dynamics and show that the corresponding ultimate limit is nearly achieved via a projective measurement of the spin-squeezed collective spin operator. We also briefly discuss the difference between our protocol and standard estimation schemes, where the state preparation time is neglected.


Spin-crossover behavior in cyanide-bridged iron(II)-gold(I) bimetallic 2D Hofmann-like metal-organic frameworks.
The synthesis and characterization of new two-dimensional (2D) cyanide-bridged iron(II)-gold(I) bimetallic coordination polymers formulated, {Fe(3-Xpy)2[Au(CN)2]2} (py = pyridine; X = F (1), Cl (2), Br (3), and I (4)) and the clathrate derivative {Fe(3-Ipy)2[Au(CN)2]2}.1/2(3-Ipy) (5), are reported. The iron(II) ion lies in pseudoctahedral [FeN6] sites defined by four [Au(CN)2](-) bridging ligands and two 3-Xpy ligands occupying the equatorial and axial positions, respectively. Although only compounds 2 and 4 can be considered strictly isostructurals, all of the components of this family are made up of parallel stacks of corrugated {Fe[Au(CN)2]2}n grids. The grids are formed by edge sharing of {Fe4[Au(CN)2]4} pseudosquare moieties. The stacks are constituted of double layers sustained by short aurophilic contacts ranging from 3.016(2) to 3.1580(8) A. The Au...Au distances between consecutive double layers are in the range of 5.9562(9)-8.790(2) A. Compound 5, considered a clathrate derivative of 4, includes one-half of a 3-Ipy molecule per iron(II) atom between the double layers. Compound 1 undergoes a half-spin transition with critical temperatures Tc downward arrow = 140 K and Tc upward arrow = 145 K. The corresponding thermodynamic parameters derived from differential scanning calorimetry (DSC) are Delta H = 9.8 +/- 0.4 kJ mol(-1) and Delta S = 68.2 +/- 3 J K mol(-1). This spin transition is accompanied by a crystallographic phase transition from the monoclinic P2(1)/c space group to the triclinic P1 space group. At high temperatures, where 1 is 100% high-spin, there is only one crystallographically independent iron(II) site. In contrast, the low temperature structural analysis shows the occurrence of two crystallographically independent iron(II) sites with equal population, one high-spin and the other low-spin. Furthermore, 1 undergoes a complete two-step spin transition at pressures as high as 0.26 GPa. Compounds 2- 4 are high-spin iron(II) complexes according to their magnetic and [FeN6] structural characteristics. Compound 5, characterized for having two different iron(II) sites, displays a two-step spin transition with critical temperatures of Tc(1) = 155 K, Tc(2) downward arrow = 97 K, and Tc(2) upward arrow = 110 K. This change of spin state takes place in both sites simultaneously. All of these results are compared and discussed in the context of other {Fe(L) x [M(I)(CN)2]} coordination polymers, particularly those belonging to the homologous compounds {Fe(3-Xpy)2[Ag(CN)2]2} and their corresponding clathrate derivatives.


Circadian onset and prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA).
Many acute cardiovascular events such as myocardial infarction (MI) follow circadian rhythms. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a newly noticed entity with limited data on onset pattern and its impact on prognosis. In this observational study of Swedish MINOCA patients registered in the SWEDEHEART registry between 2003-2013 and followed until December 2013 we identified 9,092 unique patients with MINOCA out of 199,163 MI admissions in total. Incidence rate ratios (IRR) were calculated for whole hours, parts of the day, weekdays, months, seasons and major holidays. The mean age was 65.5 years, 62.0% were women and 16.6% presented with STEMI. The risk for MINOCA proved to be most common in the morning (IRR = 1.70, 95% CI [1.63-1.84]) with a peak at 08.00 AM (IRR = 2.25, 95% CI [1.96-2.59]) and on Mondays (IRR = 1.28, 95% CI [1.18-1.38]). No altered risk was detected during the different seasons, the Christmas and New Year holidays or the Swedish Midsummer festivities. There was no association between time of onset of MINOCA and short- or long-term prognosis. The onset of MINOCA shows a circadian and circaseptan variation with increased risk at early mornings and Mondays, similar to previous studies on all MI, suggesting stress related triggering. However, during holidays were traditional MI increase, we did not see any increase for MINOCA. No association was detected between time of onset and prognosis, indicating that the underlying pathological mechanisms of MINOCA and the quality of care are similar at different times of onset but triggering mechanism may be more active early mornings and Mondays.


Origin myths in Bioethics: constructing sources, motives and reason in Bioethic(s).
Bioethics, the term now usually standing in for Biomedical Ethics, is a field of medical anthropological engagement. While many anthropologists and other social scientists work with bioethicists and physicians, this paper instead takes Bioethics as a topic of cultural research from the perspective of Cultural Bioethics and Interpretive Medical Anthropology. Application of useful findings of vintage anthropological research in cultural anthropology and the anthropology of religion and an interpretive lens reveal a field without a single origin or unified methodology. The paper suggests the appropriateness of a literal meaning of current conceptual commonality of the term Bioethics: that the term does in fact refer to a plurality of distinct enterprises with distinct origins and, hence, justifications.


Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients.
Intensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by "cytokine storms" and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.


Influence of maternal stature, pregnancy age, and infant birth weight on growth during childhood in Yucatan, Mexico: a test of the intergenerational effects hypothesis.
In developing nations, obesity has increased dramatically in the last decade, but a high prevalence of stunting still coexists. The intergenerational influences hypothesis (IIH) is one explanation for this. We test the IIH regarding variation in maternal stature, mother's age at pregnancy, and infant birth weight in relation to risk for overweight and stunting in 206 Maya children (4-6 years old) from Mérida, Yucatan, Mexico. The Maya children are compared with growth references (Frisancho 2008: Anthropometric Standards: An Interactive Nutritional Reference of Body Size and Body Composition for Children and Adults. Ann Arbor, MI: The University of Michigan Press. 335 pp) for height, weight, and body mass index (BMI). Almost 70% of the mothers are shorter than 150 cm. Mothers' height and child's birth weight predict overweight. Children with a mother shorter than 150 cm are less than half as likely (OR = 0.44) to be overweight compared to children whose mothers are equal to or taller than 150 cm. Children with birth weights below 3,000 g are only a third as likely to be overweight (OR = 0.28) than their peers within the range of normal birth weight (3,000-3,500 g). Sex of the child, mother's height, and birth weight predict stunting. Girls are only 40% as likely as boys to be stunted. Children with a mother below 150 cm are 3.6 times more likely of being stunted. Children with birth weights below 3000 g are over 3 times more likely to be stunted relative to children with birth weights within the normal range. Mother's age at pregnancy is not a predictor of overweight or stunting. Our findings conform the IIH and with similar studies of populations undergoing nutritional/epidemiological transitions from traditional to globalized lifestyles.


Robust neuro-sliding mode multivariable control strategy for powered wheelchairs.
This paper proposes an advanced robust multivariable control strategy for a powered wheelchair system. The new control strategy is based on a combination of the systematic triangularization technique and the robust neuro-sliding mode control approach. This strategy effectively copes with parameter uncertainties and external disturbances in real-time in order to achieve robustness and optimal performance of a multivariable system. This novel strategy reduces coupling effects on a multivariable system, eliminates chattering phenomena, and avoids the plant Jacobian calculation problem. Furthermore, the strategy can also achieve fast and global convergence using less computation. The effectiveness of the new multivariable control strategy is verified in real-time implementation on a powered wheelchair system. The obtained results confirm that robustness and desired performance of the overall system are guaranteed, even under parameter uncertainty and external disturbance effects.


Higher proportion of non-classical and intermediate monocytes in newly diagnosed multiple myeloma patients in Egypt: A possible prognostic marker.
Interaction between multiple myeloma (MM) cells and proximal monocytes is expected during plasma cell proliferation. However, the role of monocyte subsets in the disease progression is unknown. This study evaluated circulating monocyte populations in MM patients and their correlation with disease severity. Peripheral monocytes from 20 patients with MM attending Assiut University Hospital in Assiut, Egypt, between October 2018 and August 2019 were processed using a flow cytometry procedure and stratified using the intensity of expression of CD14 and CD16 into classical (CD16-CD14++), intermediate (CD16+CD14++), and non-classical (CD16++CD14+) subsets. The data were compared with data from 20 healthy control participants with comparable age and sex. In patients with MM, the percentage of classical monocytes was significantly lower (mean ± standard error: 77.24 ± 0.66 vs 83.75 ± 0.5), while those of non-classical (12.44 ± 0.5 vs 8.9 ± 0.34) and intermediate (10.3 ± 0.24 vs 7.4 ± 0.29) monocytes were significantly higher when compared with those of controls (all p < 0.0001). Proportions of non-classical and intermediate monocytes correlated positively with serum levels of plasma cells, M-protein, calcium, creatinine and lactate dehydrogenase, and correlated negatively with the serum albumin level. Proportions of classical monocytes correlated positively with albumin level and negatively correlated with serum levels of M-protein, plasma cells, calcium, creatinine, and lactate dehydrogenase. Circulating monocyte subpopulations are skewed towards non-classical and intermediate monocytes in MM patients, and the intensity of this skewness increases with disease severity.


How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.
Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.


[Fas receptor expression on peripheral blood T lymphocytes in patients with secondary progressive multiple sclerosis].
The percentages of CD4, CD8 subsets and Fas co-expression on them were assessed in secondary progressive multiple sclerosis (MS) patients and in control group. The MS patients were subdivided into two groups. The first group--active, consisted of patients who progressed by one or more degrees on EDSS scale in the preceding year, while the second group--stable, consisted of patients who showed no progression of the disease in the same period of time. Quantitative assessment of the individual subsets and Fas co-expression was carried out with the use of monoclonal anti-CD4, anti-CD8, as well as anti-CD95 antibodies, and Pas/Dako, Galaxy flow cytometer. There were no significant differences in CD4, CD8 subsets among the active, stable MS patients, and the control group. In the active MS group Fas co-expression on both subsets was significantly higher, as compared to controls. In the stable MS group, as compared to controls, a significantly higher Fas co-expression on CD8 subsets was observed. The investigation of Fas receptor expression on T lymphocytes in peripheral blood may be useful in order to monitor the progression of clinical activity in secondary progressive MS.


Loneliness during the post-confinement period: The significance of social living conditions for stress biomarkers and memory.
In the aftermath of the COVID-19 lockdown, concerns about the impact of loneliness and reduced social interactions on mental health have arisen. This study explored the repercussions of post-lockdown social restrictions across psychological (loneliness, perceived stress, and depressive symptoms), biological (hair cortisol and cardiovascular activity), and cognitive dimensions (subjective memory complaints and working, declarative, and prospective memory), with a specific emphasis on perceived loneliness and the living situation. The study included 45 students: 23 (mean age = 25.69 years) in the Alone Group (AG), who experienced significant family changes and international relocation, and 22 (mean age = 25.50 years) in the Not Alone Group (NAG), who maintained their nuclear family and did not move from their home country. We assessed heart rate variability (HRV) before, during, and after immediate memory evaluations using time-domain (the square root of the mean, RMSSD) measures. The analysis revealed no significant group differences in telematic contact with family and friends, perceived stress, or depression. However, the AG participants reported fewer face-to-face interactions and greater perceived loneliness compared to the NAG. Additionally, the AG group exhibited slightly higher hair cortisol levels and worse working memory (WM) and prospective memory (PM) performance. Importantly, no significant associations were observed between memory outcomes and stress biomarkers. However, a significant interaction effect of loneliness in the relationship between hair cortisol levels and PM was found. That is, hair cortisol concentrations were negatively related to PM when participants perceived high and moderate loneliness. This interaction was absent in the working and declarative memory domains. In summary, these findings underscore the intricate interplay between loneliness, cortisol, and memory, emphasizing the need for comprehensive research on the complex mechanisms governing these multifaceted relationships.


Barriers to self-management of diabetes: a qualitative study among low-income minority diabetics.
Diabetes self-management is a key element in the overall management of diabetes. Identifying barriers to disease self-management is a critical step in achieving optimal health outcomes. Our goal was to explore patients' perceptions about barriers to self-management of diabetes that could possibly help explain poor health outcomes among minority patients. Four focus groups were conducted among 31 predominately African American patients with diabetes who were enrolled in the Baltimore Cardiovascular Partnership Study, a NIH-funded multiyear prospective partnership study. The topic guide consisted of a series of open-ended questions about knowledge of current health status, medication use, continuity of care, blood glucose level and nutrition. The focus groups confirmed that previously reported barriers to self-management persisted and identified new concerns that could be associated with poor health outcomes among minority patients with diabetes. Attitudes, perceptions and behaviors surrounding diabetes and self-management of the condition did vary across individuals, however, the variation appeared to reflect the individual's knowledge and opinions rather than patient's age, sex, or culture. The primary barrier to diabetes self-management resulted from lack of knowledge of target blood glucose and blood pressure. Several participants found some of the health information to be quite confusing. Diabetes is a major public health concern and the lack of awareness of target blood glucose and blood pressure further complicates the problem. The limited health literacy seen in this study could help explain several of the barriers to self-management. The barriers to self-management identified in this qualitative study are amenable to intervention that could improve health outcomes.


Detection of Low-Frequency Mutations and Identification of Heat-Induced Artifactual Mutations Using Duplex Sequencing.
We present a genome-wide comparative and comprehensive analysis of three different sequencing methods (conventional next generation sequencing (NGS), tag-based single strand sequencing (e.g., SSCS), and Duplex Sequencing for investigating mitochondrial mutations in human breast epithelial cells. Duplex Sequencing produces a single strand consensus sequence (SSCS) and a duplex consensus sequence (DCS) analysis, respectively. Our study validates that although high-frequency mutations are detectable by all the three sequencing methods with the similar accuracy and reproducibility, rare (low-frequency) mutations are not accurately detectable by NGS and SSCS. Even with conservative bioinformatical modification to overcome the high error rate of NGS, the NGS frequency of rare mutations is 7.0 × 10-4. The frequency is reduced to 1.3 × 10-4 with SSCS and is further reduced to 1.0 × 10-5 using DCS. Rare mutation context spectra obtained from NGS significantly vary across independent experiments, and it is not possible to identify a dominant mutation context. In contrast, rare mutation context spectra are consistently similar in all independent DCS experiments. We have systematically identified heat-induced artifactual variants and corrected the artifacts using Duplex Sequencing. Specific sequence contexts were analyzed to examine the effects of neighboring bases on the accumulation of heat-induced artifactual variants. All of these artifacts are stochastically occurring rare mutations. C > A/G > T, a signature of oxidative damage, is the most increased (170-fold) heat-induced artifactual mutation type. Our results strongly support the claim that Duplex Sequencing accurately detects low-frequency mutations and identifies and corrects artifactual mutations introduced by heating during DNA preparation.


Exploring (bio)catalytic activities of structurally characterised Cu(ii) and Mn(iii) complexes: histidine recognition and photocatalytic application of Cu(ii) complex and derived CuO nano-cubes.
Structurally characterised two polymeric complexes of Cu(ii) (3) and Mn(iii) (4) of the ligand L (2-(((2-(phenylamino)ethyl)imino)methyl)phenol) have been explored for catecholase-like activity, fluorescence recognition of histidine and catalytic activity towards coupling of aryl iodides with benzamide, leading to N-arylbenzamides. CuO nano-cubes (NCs) prepared by thermal decomposition of the Cu(ii) complex function as photocatalysts for the degradation of methylene blue. Cube-like morphology of CuO nanocrystal and flake-shaped micrometer order Cu(ii) complex have been established from the field emissive scanning electron microscopy (FESEM) images.


Some guidelines for conducting a health fair.
Health professionals are being asked with increasing frequency to participate in, or to conduct, health fairs. There is, however, a lack of published practical advice available to persons undertaking such an event for the first time. Based upon my experience in this area, participants are advised to (a) clearly define in advance the objectives to be achieved by this activity, (b) give careful attention to the timing, location, and financing of the event, (c) encourage the active participation in the event of both professionals and lay persons in the community, (d) pay particular attention to publicizing the event, since the fair's success will be directly related to visitor attendance, and (e) evaluate the event to determine whether the sponsors' objective were met, whether additional health fairs should be conducted, and what changes should be made when similar events are held in the future.


Boron-Doped Silicon Diatom Frustules as a Photocathode for Water Splitting.
An effective solar-powered silicon device for hydrogen production from water splitting is a priority in light of diminishing fossil fuel vectors. There is increasing demand for nanostructuring in silicon to improve its antireflective properties for efficient solar energy conversion. Diatom frustules are naturally occurring biosilica nanostructures formed by biomineralizing microalgae. Here, we demonstrate magnesiothermic conversion of boron-doped silica diatom frustules from Aulacoseira sp. into nanostructured silicon with retention of the original shape. Hydrogen production was achieved for boron-doped silicon diatom frustules coated with indium phosphide nanocrystal layers and an iron sulfur carbonyl electrocatalyst.


Polyomavirus large T-antigen binds the "pRb related' protein p130 through sequences in conserved region 2.
The transforming potential of DNA tumor viruses derives mainly from the ability of their encoded oncogene products to interact with cellular proteins. Many of these viral oncoproteins share regions of sequence similarity, designated conserved region 1 and 2, which have been implicated in complex formation with pRb, the product of the retinoblastoma tumor suppressor gene, and related p107 and p130 species. It has now been shown that the EIA protein of adenovirus is able to bind to all three pRb-related proteins through sequences in conserved region 1 and 2. We have shown previously that polyomavirus large T-antigen also interacts with pRb and p107 in vitro. The pRb and p107 binding domains reside between residues 141, 158 which include conserved region 2. In the present study, we demonstrate that polyomavirus large T-antigen also interacted with p130 in vitro through the same sequences in conserved region 2.


Efficacy, Safety, and Preparation of Standardized Parenteral Nutrition Regimens: Three-Chamber Bags vs Compounded Monobags-A Prospective, Multicenter, Randomized, Single-Blind Clinical Trial.
Parenteral nutrition (PN) covering the need for carbohydrates, amino acids, and lipids can either be compounded from single nutrients or purchased as an industrially manufactured ready-to-use regimen. This study compares a commercially available 3-chamber bag (study group) with a conventionally compounded monobag regarding nutrition efficacy, safety, and regimen preparation time. This prospective, randomized, single-blind study was conducted at 5 Chinese hospitals from October 2010-October 2011. Postsurgical patients requiring PN for at least 6 days were randomly assigned to receive the study or control regimen. Plasma concentrations of prealbumin and C-reactive protein (CRP), regimen preparation time, length of hospital stay (LOS), 30-day mortality, safety laboratory parameters, and adverse events (AEs) were recorded. In total, 240 patients (121 vs 119 in study and control groups) participated in this study. Changes in prealbumin concentrations during nutrition support (ΔPrealb(StudyGroup) = 2.65 mg/dL, P < .001 vs ΔPrealb(ControlGroup) = 0.27 mg/dL, P = .606) and CRP values were comparable. Regimen preparation time was significantly reduced in the study group by the use of 3-chamber bags (t(StudyGroup) = 4.90 ± 4.41 minutes vs t(ControlGroup) = 12.13 ± 5.62 minutes, P < .001). No differences were detected for LOS, 30-day mortality, safety laboratory parameters, and postoperative AEs (37 vs 38 in study and control groups). The PN regimen provided by the 3-chamber bag was comparable to the compounded regimen and safe in use. Time savings during regimen preparation indicates that use of 3-chamber bags simplifies the process of regimen preparation.


Mechanical modeling of red blood cells during optical stretching.
Mechanical properties of red blood cells (RBCs) play an important role in regulating cellular functions. Many recent researches suggest that the cell properties or deformability may be used as a diagnostic indicator for the onset and progression of some human diseases. Although optical stretcher (OS) has emerged as an effective tool to investigate the cell mechanics of RBCs, little is known about the deformation behavior of RBCs in an OS. To address this problem, the mechanical model proposed in our previous work is extended in this paper to describe the mechanical responses of RBCs in the OS. With this model, the mechanical responses, such as the tension distribution, the effect of cell radius, and the deformed cell shapes, can be predicted. It is shown that the results obtained from our mechanical model are in good agreement with the experimental data, which demonstrates the validity of the developed model. Based on the derived model, the mechanical properties of RBCs can be further obtained. In conclusion, this study indicates that the developed mechanical model can be used to predict the deformation responses of RBCs during optical stretching and has potential biomedical applications such as characterizing cell properties and distinguishing abnormal cells from normal ones.


A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2.
The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. We previously identified and partially purified a mammalian Mediator complex from rat liver nuclei (Brower, C.S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause, A., Stearman, R., Klausner, R.D., Malik, S., Lane, W.S., Sorokina, I., Roeder, R.G., Conaway, J.W., and Conaway, R.C. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 10353-10358). Analysis by tandem mass spectrometry of proteins present in the most highly purified rat Mediator fractions led to the identification of a collection of new mammalian Mediator subunits, as well as several potential Mediator subunits including a previously uncharacterized protein encoded by the FLJ10193 open reading frame. In this study, we present direct biochemical evidence that the FLJ10193 protein, which we designate Med25, is a bona fide subunit of the mammalian Mediator complex. In addition, we present evidence that Med25 shares structural and functional properties with Saccharomyces cerevisiae Mediator subunit Cse2 and may be a mammalian Cse2 ortholog. Taken together, our findings identify a novel mammalian Mediator subunit and shed new light on the architecture of the mammalian Mediator complex.


Murine models for HIV vaccination and challenge.
HIV-1 only infects humans and chimpanzees. SIV or SHIV are, therefore, used as models for HIV in rhesus, cynomologus and pigtail macaques. Since conducting experiments in primate models does not fully mimic infection or vaccination against HIV-1 and is expensive, there is a great need for small-animal models in which it is possible to study HIV-1 infection, immunity and vaccine efficacy. This review summarizes the available murine models for studying HIV-1 infection with an emphasis on our experience of the HIV-1-infected-cell challenge as a model for evaluating candidate HIV-1 vaccines. In the cell-based challenge model, several important factors that, hopefully, can be related to vaccine efficacy in humans were discovered: the efficiency of combining plasmid DNA representing several of the viral genes originating from multiple clades of HIV-1, the importance of adjuvants activating innate and induced immunity and the enhanced HIV eradication by drug-conjugated antibody.


Pyruvate dehydrogenase activation in inactive muscle during and after maximal exercise in men.
Pyruvate dehydrogenase activity (PDHa) and acetyl-group accumulation were examined in the inactive deltoid muscle in response to maximal leg exercise in men. Seven subjects completed three consecutive 30-s bouts of maximal isokinetic cycling, with 4-min rest intervals between bouts. Biopsies of the deltoid were obtained before exercise, after bouts 1 and 3, and after 15 min of rest recovery. Inactive muscle lactate (LA) and pyruvate (PYR) contents increased more than twofold (P < 0.05) after exercise (bout 3) and remained elevated after 15 min of recovery (P < 0.05). Increased PYR accumulation secondary to LA uptake by the inactive deltoid was associated with greater PDHa, which progressively increased from 0.71 +/- 0.23 mmol. min-1. kg wet wt-1 at rest to a maximum of 1.83 +/- 0.30 mmol. min-1. kg wet wt-1 after bout 3 (P < 0.05) and remained elevated after 15 min of recovery (1.63 +/- 0.24 mmol. min-1. kg wet wt-1; P < 0.05). Acetyl-CoA and acetylcarnitine accumulations were unaltered. Increased PDHa allowed and did not limit the oxidation of LA and PYR in inactive human skeletal muscle after maximal exercise.


Regeneration of the vocal fold using autologous mesenchymal stem cells.
The aim of this study was to regenerate the injured vocal fold by means of selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle dogs were used for this experiment. Selective incubation of MSCs from bone marrow was done. These MSCs were submitted to 3-dimensional incubation in 1% hydrochloric acid atelocollagen. Three-dimensional incubated MSCs were injected into the left vocal fold, and atelocollagen only was injected into the right vocal fold of the same dog as a control. Four days after injection, the posterior parts of the vocal folds were incised. The regeneration of the vocal fold was estimated by morphological and histologic evaluations. Our results showed that 3-dimensional incubated MSCs were useful in the regeneration of the injured vocal fold. This study shows that damaged tissues such as an injured vocal fold would be able to be regenerated by tissue engineering.


The morphology of smoke inhalation injury in sheep.
Pulmonary injury resulting from inhalation of chemical and particulate products of incomplete combustion is one of the principal determinants of mortality following burn injury. In this study, the histopathology of inhalation injury was examined in sheep. Mild, moderate, or severe smoke injury was produced in anesthetized sheep by insufflation with various doses of ambient temperature smoke, generated by burning polyethylene, wood pulp, and nonwoven cellulose pads. A total of 64 sheep were exposed and evaluated at times ranging from 15 minutes to 4 weeks after exposure. Morphologic changes in the lungs were studied using light microscopy and both transmission and scanning electron microscopy. The primary, dose-responsive injury observed was acute cell membrane damage in the trachea and bronchi leading to edema, progressive necrotic tracheobronchitis with pseudomembrane formation, and airway obstruction. These inflammatory and occlusive effects were followed by congestion, alveolar space edema, atelectasis, and bronchopneumonia. Morphologic changes occurring in the alveolar epithelium following high smoke dosage included intracellular edema in type-I cells, changes in the membrane-bound vacuoles of type-II cells, and septal thickening caused by interstitial edema. No capillary endothelial changes were observed.


Increased expression of the remodeling- and tumorigenic-associated factor osteopontin in pyramidal neurons of the Alzheimer's disease brain.
Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimer's disease (AD) compared with age-matched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-beta load (r(2) = 0.25; P < 0.05; n = 20) and aging (r(2) = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-beta load, but not age. While the functional consequences of this amyloid-beta associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-beta generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD.


Chemical modification of sarcoplasmic reticulum. Stimulation of Ca2+ release.
Pretreatment of sarcoplasmic membranes with acetic or maleic anhydrides, which interact principally with amino groups, resulted in an inhibition of Ca2+ accumulation and ATPase activity. The presence of ATP, ADP or adenosine 5'-[beta, gamma-imido]triphosphate in the modification medium selectively protected against the inactivation of ATPase activity by the anhydride but did not protect against the inhibition of Ca2+ accumulation. Acetic anhydride modification in the presence of ATP appeared to increase specifically the permeability of the sarcoplasmic reticulum membrane to Ca2+ but not to sucrose, Tris, Na+ or Pi. The chemical modification stimulated a rapid release of Ca2+ from sarcoplasmic reticulum vesicles passively or actively loaded with calcium, from liposomes reconstituted with the partially purified ATPase fraction but not from those reconstituted with the purified ATPase. The inactivation of Ca2+ accumulation by acetic anhydride (in the presence of ATP) was rapid and strongly pH-dependent with an estimated pK value above 8.3 for the reactive group(s). The negatively charged reagents pyridoxal 5-phosphate and trinitrobenzene-sulphonate, which also interact with amino groups, did not stimulate Ca2+ release. Since these reagents do not penetrate the sarcoplasmic reticulum membranes, it is proposed that Ca2+ release is promoted by modification of internally located, positively charged amino group(s).


Transtemporal power- and frequency-based color-coded duplex sonography of cerebral veins and sinuses.
To determine the ability of transtemporal power- and frequency-based transcranial color-coded duplex sonography to aid in the assessment of cerebral veins and sinuses, as well as to provide reference data for flow direction and velocity. Using a color duplex device equipped with a 2.0/2.5-MHz sector scan, we insonated 120 healthy volunteers and three patients with cerebral venous thrombosis. In subjects 20 to 59 years old, deep middle cerebral veins were identified in 88%, basal veins in 97%, straight sinuses in 60%, and transverse sinuses in 42%. The corresponding values for subjects 60 to 79 years old were 53%, 86%, 23%, and 20%, respectively. Velocities were highest in transverse and straight sinuses, slower in basal veins, and slowest in deep middle cerebral veins. Flow was directed lateromedially in the deep middle cerebral vein, rostrocaudally in the basal vein and straight sinus, and mediolaterally in the transverse sinus. Two patients with straight sinus thromboses showed reversed flow direction in the basal veins, and one patient with superior sagittal sinus thrombosis showed elevated velocities in a deep middle cerebral vein. Transtemporal power- and frequency-based color-coded duplex sonography enabled imaging and velocity measurements in deep cerebral veins in subjects 20 to 59 years old, but detection of the straight and transverse sinuses was low. In older subjects, only the basal vein was regularly assessed.


Open source tool for prediction of genome wide protein-protein interaction network based on ortholog information.
Protein-protein interactions are crucially important for cellular processes. Knowledge of these interactions improves the understanding of cell cycle, metabolism, signaling, transport, and secretion. Information about interactions can hint at molecular causes of diseases, and can provide clues for new therapeutic approaches. Several (usually expensive and time consuming) experimental methods can probe protein - protein interactions. Data sets, derived from such experiments make the development of prediction methods feasible, and make the creation of protein-protein interaction network predicting tools possible. Here we report the development of a simple open source program module (OpenPPI_predictor) that can generate a putative protein-protein interaction network for target genomes. This tool uses the orthologous interactome network data from a related, experimentally studied organism. Results from our predictions can be visualized using the Cytoscape visualization software, and can be piped to downstream processing algorithms. We have employed our program to predict protein-protein interaction network for the human parasite roundworm Brugia malayi, using interactome data from the free living nematode Caenorhabditis elegans. The OpenPPI_predictor source code is available from http://tools.neb.com/~posfai/.


Variance analysis refines overhead cost control.
Many healthcare organizations may not fully realize the benefits of standard cost accounting techniques because they fail to routinely report volume variances in their internal reports. If overhead allocation is routinely reported on internal reports, managers can determine whether billing remains current or lost charges occur. Healthcare organizations' use of standard costing techniques can lead to more realistic performance measurements and information system improvements that alert management to losses from unrecovered overhead in time for corrective action.


Constrained water access to the active site of cytochrome P450 from the piezophilic bacterium Photobacterium profundum.
Living species inhabiting ocean deeps must adapt to high hydrostatic pressure. This adaptation, which must enable functioning under conditions of promoted protein hydration, is especially important for proteins such as cytochromes P450 that exhibit functionally important hydration-dehydration dynamics. Here we study the interactions of substrates with cytochrome P450-SS9, a putative fatty acid hydroxylase from the piezophilic bacterium Photobacterium profundum SS9, and characterize the protein's barotropic properties. Comparison of P450-SS9 with cytochrome P450BM-3, a mesophilic fatty acid hydroxylase, suggests that P450-SS9 is characterized by severely confined accessibility and low water occupancy of the active site. This feature may reveal a mechanism of structural adaptation of the piezophilic enzyme. We also demonstrate that saturated and unsaturated fatty acids exert opposite effects on solvent accessibility and hydration of the active site. Modulation of the protein conformation by fatty acids is hypothesized to have an important physiological function in the piezophile.


Fast triggering in high-energy physics experiments using hardware neural networks.
High-energy physics experiments require high-speed triggering systems capable of performing complex pattern recognition at rates of Megahertz to Gigahertz. Neural networks implemented in hardware have been the solution of choice for certain experiments. The neural triggering problem is presented here via a detailed look at the H1 level 2 trigger at the HERA accelerator, Hamburg, Germany, followed by a section on the importance of hardware preprocessing for such systems, and finally some new architectural ideas for using field programmable gate arrays in very high-speed neural-network triggers at upcoming experiments.


Maintenance-Free Smart Hand Dynamometer.
Grip strength measurement is one of the most accessible methods for measuring overall muscle strength, and many studies have shown a link between low grip strength and future diseases. In recent years, devices for grip strength measurements that can connect to digital devices for automatic data recording have been developed. However, such devices have high development costs and require daily maintenance. Therefore, this we propose a grip strength measurement method using the capacitance sensor of a smartphone and no electronic parts on the measurement device side.