[Remarkable domestic animal breeds in California].
In the United States, especially in California, there is a surprising variety of farm animal breeds. This multitude of different forms is a result of the history of this State. Some breeds came from other countries, others were developed from feral animals and yet others were created in this state by crossing and selective breeding. Several of these breeds soon attained a high level of performance and they were exported to many other countries. Others remained primitive landraces with special adaptation or had unusual morphological characteristics. There are some breeds that influenced the history of North America considerably. This is only one reason why these breeds should be sustained as a cultural heritage.


The effect of acute sleep deprivation on skeletal muscle protein synthesis and the hormonal environment.
Chronic sleep loss is a potent catabolic stressor, increasing the risk of metabolic dysfunction and loss of muscle mass and function. To provide mechanistic insight into these clinical outcomes, we sought to determine if acute sleep deprivation blunts skeletal muscle protein synthesis and promotes a catabolic environment. Healthy young adults (N = 13; seven male, six female) were subjected to one night of total sleep deprivation (DEP) and normal sleep (CON) in a randomized cross-over design. Anabolic and catabolic hormonal profiles were assessed across the following day. Postprandial muscle protein fractional synthesis rate (FSR) was assessed between 13:00 and 15:00 and gene markers of muscle protein degradation were assessed at 13:00. Acute sleep deprivation reduced muscle protein synthesis by 18% (CON: 0.072 ± 0.015% vs. DEP: 0.059 ± 0.014%·h-1 , p = .040). In addition, sleep deprivation increased plasma cortisol by 21% (p = .030) and decreased plasma testosterone by 24% (p = .029). No difference was found in the markers of protein degradation. A single night of total sleep deprivation is sufficient to induce anabolic resistance and a procatabolic environment. These acute changes may represent mechanistic precursors driving the metabolic dysfunction and body composition changes associated with chronic sleep deprivation.


TRH and TRH-OH in the pancreas of adult and newborn rats.
TRH and its metabolite TRH-OH have been measured by specific radioimmunoassays in acid extracts of pancreas in adults and developing rats. TRH and TRH-OH immunoreactivity had the same ontogenic pattern with a maximal concentration on day 4 followed by a progressive return towards adult levels on day 20. A significant linear correlation was found between TRH levels and the TRH/TRH-OH ratio. The range of TRH/TRH-OH ratio varied from 136 +/- 1.6, at the peak of concentrations of both peptides, to 18 +/- 3.9 on day 20. Pancreatic TRH and TRH-OH had the same elution pattern as corresponding synthetic peptides both on Biogel P2 and high-pressure liquid chromatography. The origin of TRH-OH as well as its potential function need further investigations.


Evaluation of clinical full field digital mammography with the task specific system-model-based Fourier Hotelling observer (SMFHO) SNR.
The purpose of this work is to evaluate the performance of the image acquisition chain of clinical full field digital mammography (FFDM) systems by quantifying their image quality, and how well the desired information is captured by the images. The authors present a practical methodology to evaluate FFDM using the task specific system-model-based Fourier Hotelling observer (SMFHO) signal to noise ratio (SNR), which evaluates the signal and noise transfer characteristics of FFDM systems in the presence of a uniform polymethyl methacrylate phantom that models the attenuation of a 6 cm thick 20/80 breast (20% glandular/80% adipose). The authors model the system performance using the generalized modulation transfer function, which accounts for scatter blur and focal spot unsharpness, and the generalized noise power spectrum, both estimated with the phantom placed in the field of view. Using the system model, the authors were able to estimate system detectability for a series of simulated disk signals with various diameters and thicknesses, quantified by a SMFHO SNR map. Contrast-detail (CD) curves were generated from the SNR map and adjusted using an estimate of the human observer efficiency, without performing time-consuming human reader studies. Using the SMFHO method the authors compared two FFDM systems, the GE Senographe DS and Hologic Selenia FFDM systems, which use indirect and direct detectors, respectively. Even though the two FFDM systems have different resolutions, noise properties, detector technologies, and antiscatter grids, the authors found no significant difference between them in terms of detectability for a given signal detection task. The authors also compared the performance between the two image acquisition modes (fine view and standard) of the GE Senographe DS system, and concluded that there is no significant difference when evaluated by the SMFHO. The estimated human observer efficiency was 30 ± 5% when compared to the SMFHO. The results showed good agreement when compared to other model observers as well as previously published human observer data. This method generates CD curves from the SMFHO SNR that can be used as figures of merit for evaluating the image acquisition performance of clinical FFDM systems. It provides a way of creating an empirical model of the FFDM system that accounts for patient scatter, focal spot unsharpness, and detector blur. With the use of simulated signals, this method can predict system performance for a signal known exactly/background known exactly detection task with a limited number of images, therefore, it can be readily applied in a clinical environment.


Initiating the first DTP vaccination age-appropriately: a model for understanding vaccination coverage.
Our earlier research found that the strongest predictor of not being up to date on the full series of immunizations by 24 months is failure to receive the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on time. To learn more about the relationship between successful vaccination during the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life, inclusive) and an infant's early visit to the physician (before 42 days of life), we quantified children's progression through a sequence of provider visits and outcomes. This study analyzed data from 426 children living in the 57 poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the percentage of times a DTP1-AA vaccination, provider missed opportunity, or deferral for a valid contraindication occurred. Relative and attributable risks were computed to assess associations between DTP1-AA vaccination and early visits and missed opportunities. We found the following: 1) Children who made a visit before 42 days of life were more than twice as likely to receive a DTP1-AA vaccination; 2) the missed opportunity rate for children who did not make an early visit was approximately twice that of the early-visit group; and 3) well visits were more likely to result in DTP1-AA immunization than sick visits. Attributable risk calculations show that DTP1-AA vaccination rates could be increased in this population by one third if all infants had an early visit. Early in-office visits seem to make DTP1-AA vaccination more likely. These rates may be amenable to intervention by increasing early visits and reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to the recommended series may place more emphasis on early visits and result in increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.


Theoretical study of hydroxyl radical (OH˙) induced decomposition of tert-butyl methyl ether (MTBE).
We have characterized the various pathways for OH radical (OH˙) induced decomposition of tert-butyl methyl ether (MTBE) and found an oxidative pathway that leads to complete degradation under the prerequisite that OH radicals are present in excess. A simple polarizable continuum model is used to predict the behavior in an aqueous medium and the behavior is unchanged compared to that in the gas phase. The computational study has also revealed some of the fundamental aspects of hydrogen transfer from asymmetric ethers; the ˙OH assisted hydrogen abstraction has a barrier when the reaction takes place at a distance from the heteroatom, that is, at the tert-butyl group, whereas hydrogen abstraction from the methyl group proceeds without a barrier. The addition of ˙OH to (CH3)3COCH2˙ also proceeds without a barrier, and so does hydrogen abstraction from the resulting adduct ((CH3)3COCH2OH) to form (CH3)3COCH(OH)˙. However, a barrier is yet again found in the hydrogen abstraction from the latter to form (CH3)3COCH[double bond, length as m-dash]O and yet again in the formation of the formyl radical (CH3)3COC[double bond, length as m-dash]O˙ by hydrogen abstraction. The latter is the last step before the final stage of complete oxidation of MTBE to form CO2.


Deep learning based classification of dynamic processes in time-resolved X-ray tomographic microscopy.
Time-resolved X-ray tomographic microscopy is an invaluable technique to investigate dynamic processes in 3D for extended time periods. Because of the limited signal-to-noise ratio caused by the short exposure times and sparse angular sampling frequency, obtaining quantitative information through post-processing remains challenging and requires intensive manual labor. This severely limits the accessible experimental parameter space and so, prevents fully exploiting the capabilities of the dedicated time-resolved X-ray tomographic stations. Though automatic approaches, often exploiting iterative reconstruction methods, are currently being developed, the required computational costs typically remain high. Here, we propose a highly efficient reconstruction and classification pipeline (SIRT-FBP-MS-D-DIFF) that combines an algebraic filter approximation and machine learning to significantly reduce the computational time. The dynamic features are reconstructed by standard filtered back-projection with an algebraic filter to approximate iterative reconstruction quality in a computationally efficient manner. The raw reconstructions are post-processed with a trained convolutional neural network to extract the dynamic features from the low signal-to-noise ratio reconstructions in a fully automatic manner. The capabilities of the proposed pipeline are demonstrated on three different dynamic fuel cell datasets, one exploited for training and two for testing without network retraining. The proposed approach enables automatic processing of several hundreds of datasets in a single day on a single GPU node readily available at most institutions, so extending the possibilities in future dynamic X-ray tomographic investigations.


Possible early pennsylvanian ancestor of the cycadales.
A specimen of Lesleya, previously known only as isolated sterile foliage, has been found with two rows of ovule-bearing receptacles on opposite sides of the petiole. This specimen is from the Lower Pennsylvanian (Namurian B or C) of western Illinois. The fertile portion of this specimen is similar to Phasmatocycas kansana Mamay from the Lower Permian of Kansas and Texas, which Mamay interpreted as an ancestral form to cycads. Phasmatocycas was found attached to the base of Taeniopteris by Gillespie and Pfefferkorn. The foliar portions, Lesleya and Taeniopteris, have many features in common; the major morphologic difference is curvature of the veins. Lesleya and its attached fertile petiole are proposed as ancestors of Taeniopteris and Phasmatocycas, and ultimately, the ancestors of modern cycads. This extends the age of known precursors of cycads back from the Early Permian to Early Pennsylvanian (about 320 million years ago), approximately 35 million years earlier.


Improving the Design of the Triple-Decker Motif in Red Fluorescent Proteins.
We characterize computationally a red fluorescent protein (RFP) with the chromophore (Chro) sandwiched between two aromatic tyrosine rings in a triple-decker motif. According to the original proposal [ J. Phys. Chem. Lett. 2013 , 4 , 1743 ], such a tyrosine-chromophore-tyrosine π-stacked construct can be accommodated in the green fluorescent protein (GFP). A recent study [ ACS Chem. Biol. 2016 , 11 , 508 ] attempted to realize the triple-decker motif and obtained an RFP variant called mRojoA-VYGV with two tyrosine residues surrounding the chromophore. The crystal structure showed that only a tyrosine-chromophore pair was involved in π-stacking, whereas the second tyrosine was oriented perpendicularly, edge-to-face with respect to the chromophore. We propose a more promising variant of this RFP with a perfect triple-decker unit achieved by introducing additional mutations in mRojoA-VYGV. The structures and optical properties of model proteins based on the structures of mCherry and mRojoA are characterized computationally by QM(DFT)/MM. The electronic transitions in the protein-bound chromophores are computed by high-level quantum chemical methods. According to our calculations, the triple-decker chromophore unit in the new RFP variant is stable within the protein and its optical bands are red-shifted with respect to the parent mCherry and mRojoA species.


Isolation and application of Gordonia sp. JC11 for removal of boat lubricants.
Boat lubricants are continuously released into the marine environment and thereby cause chronic oil pollution. This study aims to isolate lubricant-degrading microorganisms from Thai coastal areas as well as to apply a selected strain for removal of boat lubricants. Ten microorganisms in the genera of Gordonia, Microbacterium, Acinetobacter, Pseudomonas, Brucella, Enterococcus and Candida were initially isolated by crude oil enrichment culture techniques. The lubricant-removal activity of these isolates was investigated with mineral-based lubricants that had been manufactured for the 4-stroke diesel engines of fishing boats. Gordonia sp. JC11, the most effective strain was able to degrade 25-55% of 1,000 mg L(-1) total hydrocarbons in six tested lubricants, while only 0-15% of the lubricants was abiotically removed. The bacterium had many characteristics that promoted lubricant degradation such as hydrocarbon utilization ability, emulsification activity and cell surface hydrophobicity. For bioaugmentation treatment of lubricant contaminated seawater, the inoculum of Gordonia sp. JC11 was prepared by immobilizing the bacterium on polyurethane foam (PUF). PUF-immobilized Gordonia sp. JC11 was able to remove 42-56% of 100-1,000 mg L(-1) waste lubricant No. 2 within 5 days. This lubricant removal efficiency was higher than those of free cells and PUF without bacterial cells. The bioaugmentation treatment significantly increased the number of lubricant-degrading microorganisms in the fishery port seawater microcosm and resulted in rapid removal of waste lubricant No. 2.


Deterioration of mild anxiety and depression with Better Access treatment: implications for scaling up psychotherapy worldwide.
The Australian Medicare Better Access initiative in mental health reached one in every 10 Australians in 2021 (more than 2.6 million people) with interventions targeted at mild-to-moderate anxiety and depression, provided by general practitioners, allied health professionals, and/or psychiatrists, at a cost of AUD1.2 billion. However, the overall mental health of the Australian population has not improved since the introduction of Better Access. The benefits of population-scale mental health interventions (medications and psychotherapies) might have been overestimated for milder conditions, and the iatrogenic potential underestimated. A recent evaluation of Better Access found that mild anxiety and depressive symptoms were threefold more likely to worsen (32%) rather than improve (10%). Better Access might be targeted more cost-effectively towards severe and complex conditions, for which treatment appears to have superior risk-benefit ratios. These findings have implications for similar initiatives worldwide, such as those proposed by the World Health Organization.


Evaluation of the in vitro activity of tigecycline against multiresistant Gram-positive cocci containing tetracycline resistance determinants.
This study was undertaken to test the in vitro activity of tigecycline against 117 clinically relevant Gram-positive pathogens and to correlate this activity with their resistance gene content. Overall, tigecycline showed a minimal inhibitory concentration (MIC) range of 0.015-0.5mg/L, able to inhibit potently all multiresistant streptococci, enterococci and MR staphylococci. Tigecycline was active against methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, with MICs for 90% of the organisms (MIC(90)) of 0.25 mg/L and 0.12 mg/L, respectively, being more active than linezolid (MIC(90)=2 mg/L) and quinupristin/dalfopristin (MIC(90)=0.5 and 2-4 mg/L, respectively). Molecular characterisation of resistance determinants demonstrated the concomitant presence of different classes of genes: in particular, tet(M), erm(B) and erm(C) in Streptococcus agalactiae; tet(O), variably associated with different erm genes, in Streptococcus pyogenes; vanA, tet(M) and erm(B) in Enterococcus faecalis, and vanA and erm(B) in Enterococcus faecium. All the MRSA strains harboured SCCmec and erm genes and 50% possessed tet(K) with tet(M) genes. Staphylococcus epidermidis strains were only resistant to erythromycin. These results clearly demonstrate that tigecycline has a MIC(90) range of 0.015-0.5 mg/L both against tetracycline-susceptible and -resistant isolates carrying other resistance determinants, suggesting that this drug could play an important role in the treatment of infections caused by these multiresistant Gram-positive pathogens.


Hidden entropy production by fast variables.
We investigate nonequilibrium underdamped Langevin dynamics of Brownian particles that interact through a harmonic potential with coupling constant K and are in thermal contact with two heat baths at different temperatures. The system is characterized by a net heat flow and an entropy production in the steady state. We compare the entropy production of the harmonic system with that of Brownian particles linked with a rigid rod. The harmonic system may be expected to reduce to the rigid rod system in the infinite K limit. However, we find that the harmonic system in the K→∞ limit produces more entropy than the rigid rod system. The harmonic system has the center-of-mass coordinate as a slow variable and the relative coordinate as a fast variable. By identifying the contributions of the degrees of freedom to the total entropy production, we show that the hidden entropy production by the fast variable is responsible for the extra entropy production. We discuss the K dependence of each contribution.


Does early life exposure to antibiotics increase the risk of eczema? A systematic review.
A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta-analysis of observational studies, involving children or young adults aged 0-25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio (OR) for the 17 studies examining postnatal antibiotic exposure was 1.41 [95% confidence interval (CI) 1.30-1.53]. The pooled OR for the 10 longitudinal studies was 1.40 (95% CI 1.19-1.64), compared with a pooled OR of 1.43 (95% CI 1.36-1.51) for the seven cross-sectional studies. There was a significant dose-response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1.07 (95% CI 1.02-1.11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1.30 (95% CI 0.86-1.95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema.


Finite element simulation of implant placement following extraction of a single tooth.
The aim of the study was to assess some possible factors influencing the bone stresses and remodeling process after the placement of an implant in a postextraction socket. A finite element model of a portion of the maxilla was used. Three osseointegrated titanium dental implants with different thread profiles were placed into the extraction socket. Three different lengths, thus with different depth into the bone, were considered. Bone remodeling was simulated by using the strain energy density as the remodeling stimulus. A load with magnitude 200 N and inclination of 45° to the longitudinal axis in the lateral direction was applied directly to the implant. Both implant length and thread profile had an influence on the bone stresses, growth and loss after implantation. Longer implants reduced both the size of the bone loss area and the total bone mass loss. It is not easy to establish the relationship of the long-term success of implantation and bone turnover activity via clinical trials. After a proper clinical validation, the protocol developed using computational modeling may become a viable option to predict the clinical outcome, even on a patient-specific basis, regarding its noninvasive and time-efficient nature.


Trends and determinants of Comprehensive HIV and AIDS knowledge among urban young women in Kenya.
Sub-Saharan Africa remains the region most heavily affected by HIV. In 2008, the region accounted for 67% of HIV infections worldwide, the region also accounted for 72% of the world's AIDS-related deaths in 2008. Young people aged 15-24 years accounted for an estimated 45% of the new HIV infections. In sub-Saharan Africa, Kenya is among countries affected by the HIV and AIDS pandemic which led to the declaration of AIDS as a national disaster in 1999. Given these scenario the study was undertaken to examine trends in HIV and AIDS comprehensive knowledge and identify the main correlates of comprehensive HIV and AIDS knowledge among Kenyan urban young women. Data used was drawn from the 1993, 1998, 2003 and 2008/09 Kenya Demographic & Health Surveys. Logistic regression was used for analysis. While comprehensive HIV and AIDS knowledge is low among urban young women in Kenya, the results show a significant increase in comprehensive knowledge from 9% in 1993 to 54% in 2008/09. The strongest predictors for having comprehensive knowledge were found to be 1) education; 2) having tested for HIV; 3) knowing someone with HIV, and/or 4) having a small or moderate to great risk perception. The response to HIV and AIDS can only be successful if individuals adopt behaviours that will protect against infection. Currently, efforts are underway in Kenya to ensure that young people have comprehensive knowledge. As evident from the results, comprehensive HIV and AIDS knowledge has increased over the 15 year period among urban young women from 9% in 1993 to 54% in 2008/09. Despite this improvement, a lot more needs to be done to attain the target of 90% threshold set by UNGASS. While both young women and men should be targeted with education on HIV prevention, concerted efforts should be directed at young women as many continue to get infected due to low levels of comprehensive HIV knowledge.


Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses.
Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. An enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nose-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B cell responses to pH1N1, seasonal H1N1 (sH1N1), and avian H5N1 (aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1, and aH5N1 viruses. The 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity to not only H1N1 but also aH5N1 viruses. These findings may have important implications for future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells.


Natural aristolactams and aporphine alkaloids as inhibitors of CDK1/cyclin B and DYRK1A.
In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A.


Hemodynamic findings in 123 patients with acute myocardial infarction on admission.
Hemodynamic and clinical evaluations of 123 patients with acute myocardial infarction were performed during the first hour of admission to the hospital. In the 123 patients, the right atrial pressure was less than 10 mm Hg in 49 patients, the right atrial oxygen saturation was less than 70% in 97 patients, the arteriovenous oxygen difference was greater than 5.0 vol% in 78 patients. The arterial Po2 was less than 90 mm Hg in 101 of 107 patients who could be evaluated while breathing room air. The cardiac index was depressed below 3.0 L/min/m2 in 65 of 98 patients. The hemodynamic findings generally correlated with the clinical status of the patient; however, within each clinical class of patients there was a wide spectrum of values for each measurement evaluated. There was also considerable overlap of the values found within each clinical classification. It is concluded that hemodynamic evaluation of patients with acute myocardial infarction presents a profile of the patient which is frequently different from the profile that clinical evaluation presents. An objective hemodynamic classification of patients with acute myocardial infarction may provide a more useful index for the evaluation of the patient's prognosis and for the assessment of preventative therapy.


Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvate:flavodoxin and 2-oxoglutarate:acceptor oxidoreductases which mediate electron transport to NADP.
Helicobacter pylori, a major cause of human gastric disease, is a microaerophilic bacterium that contains neither pyruvate nor 2-oxoglutarate dehydrogenase activity. Previous studies (N. J. Hughes, P. A. Chalk, C. L. Clayton, and D. J. Kelly, J. Bacteriol. 177:3953-3959, 1995) have indicated that the major routes for the generation of acetyl coenzyme A (acetyl-CoA) and succinyl-CoA are via pyruvate:flavodoxin oxidoreductase (POR) and 2-oxoglutarate:acceptor oxidoreductase (OOR), respectively. The purified POR is a heterotetrameric protein, with subunits of 48 (PorA), 36 (PorB), 24 (PorC), and 14 (PorD) kDa. In this study OOR has been purified, and it is similarly composed of polypeptides of 43 (OorA), 33 (OorB), 24 (OorC), and 10 (OorD) kDa. Both POR and OOR are oxygen labile and are likely to be major contributors to the microaerophilic phenotype of H. pylori. Unlike POR, OOR was unable to use a previously identified flavodoxin (FldA) as an electron acceptor. Although the purified enzymes were unable to reduce NAD(P), electrons from both pyruvate and 2-oxoglutarate could reduce NADP in cell extracts, consistent with a role for these oxidoreductases in the provision of NADPH as a respiratory electron donor. The H. pylori por, oor, and fldA genes were cloned and sequenced. The deduced por gene products showed significant sequence similarity to archaeal four-subunit 2-oxoacid:acceptor oxidoreductases. However, the amino acid sequences of OorA and -B were more closely related to that of the two-subunit POR of the aerobic halophile Halobacterium halobium. Both porD and oorD encode integral ferredoxin-like subunits. POR and OOR are probably essential enzymes in H. pylori, as insertion inactivation of porB and oorA appeared to be lethal.


How Swedish breeders can substantially increase the genetic gain for the English Setter's hunting traits.
In both Sweden (Swe) and Norway (Nor), the English Setter is used for hunting. Similar field trials are arranged to give breeders information on the dogs' hunting abilities. Our main objective was to study if a joint Swe-Nor genetic evaluation can improve accuracy compared with estimation of breeding values on a national level only. Genetic parameters for six hunting traits were estimated in univariate (within country) and bivariate (across country, of equivalent traits between countries and joint pedigree) analyses utilizing 3620 Swe records from 685 dogs and 94,414 Nor records from 7175 dogs. A mixed linear animal model was used, including fixed effects of sex, type of trial, year, month and interaction between age and class of trial, and random effects of animal, permanent environment, judge and residual. Heritabilities ranged from 0.07 to 0.13 for Swe and from 0.08 to 0.18 for Nor. The accuracies were higher in the bivariate analyses, especially for dogs with Swe trial results with an average increase of 19%. If comparing selection based on a joint genetic evaluation over phenotypic results alone (which is today's method), the potential genetic gain in Swe was almost doubled. Our results suggest that a joint genetic evaluation is especially advantageous for a population with limited information, such as the English Setter population in Swe. However, it should also be beneficial for Norwegian breeders because it makes it easier for them to select Swedish dogs, potentially resulting in faster genetic gain and lowered inbreeding rate.


Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity.
The notch signaling pathway is essential for the endocrine cell fate in various tissues including the enteroendocrine system of the gastrointestinal tract. Enteroendocrine cells are one of the four major cell types found in the gastric epithelium of the glandular stomach. To understand the molecular basis of enteroendocrine cell development, we have used gene targeting in mouse embryonic stem cells to derive an EGFP-marked null allele of the bHLH transcription factor, neurogenin 3 (ngn3). In ngn3(-/-) mice, glucagon secreting A-cells, somatostatin secreting D-cells, and gastrin secreting G-cells are absent from the epithelium of the glandular stomach, whereas the number of serotonin-expressing enterochromaffin (EC) cells is decreased dramatically. In addition, ngn3(-/-) mice display intestinal metaplasia of the gastric epithelium. Thus, ngn3 is required for the differentiation of enteroendocrine cells in the stomach and the maintenance of gastric epithelial cell identity.


[Cladophilaphora bantiana brain abscess treated with voriconazole in an immunocompetent patient].
Phaeohyphomycosis is a term used to define infections caused by darkly pigmented fungi with septate hyphae which contain melanin in their cell walls. Although fungi rarely cause central nervous system (CNS) infections, the incidence of CNS infections caused by melanin-containing fungi has been increasing in the recent years. Cladophialophora bantiana is the most frequently isolated species from cerebral phaeohyphomycosis. It mostly affects adult men in the second and third decade of life and about half of the cases occurs in immunocompetent patients. In this report, the isolation of C.bantiana from brain tissue of an immunocompetent patient who was operated with the initial diagnosis of a brain abscess, was presented. A 27 year-old male patient presenting without any chronic disease was admitted to the emergency department of our hospital with the complaints of persistent headache and diplopia. Magnetic resonance imaging (MRI) showed a space-occupying lesion in the right parietal lobe and left frontal lobe. Brain abscess was diagnosed in the patient who was referred to the neurosurgery department. Treatment was initiated with ceftriaxone and metronidazole. The abscess material sent for direct microscopic examination in the mycology laboratory was stained with Gram and Giemsa and cultured in the Sabouraud dextrose agar medium (SDA) with and without antibiotics (cycloheximide and chloramphenicol). Then, it was incubated at 37°C and 25°C. Direct examination and staining revealed a septate hyphae. The patient who received liposomal amphotericin B was referred to the infectious diseases department. Surface colors of all media including SDA with cycloheximide were olive-gray to black and contained velvety colonies. Lemon-like very long and integrated chains of conidium with poor branching in cornmeal Tween 80 agar, as well as growth at 42°C in passages, positive urease test result and cycloheximide resistance suggested C.bantiana. The isolate was confirmed as C. bantiana based on its DNA sequence analysis. Minimum inhibitor concentration (MIC) values for amphotericin B, voriconazole, caspofungin, and posaconazole were 2 µg/ml, 0.03 µg/ml, 0.03 µg/ml and 0.03 µg/ml, respectively. Liposomal amphotericin B was replaced with voriconazole due to the antifungal susceptibility profile. The patient who was symptom-free was discharged at 24 days after hospitalization with oral voriconazole treatment. In conclusion, cerebral phaeohyphomycosis should be considered in immunocompetent individuals. Given the fact that early diagnosis saves lives, such specimens should promptly be sent for mycological analysis.


The reliability and validity of fatigue measures during short-duration maximal-intensity intermittent cycling.
The purpose of the present study was to assess the reliability and validity of fatigue measures, as derived from 4 separate formulae, during tests of repeat sprint ability. On separate days over a 3-week period, 2 groups of 7 recreationally active men completed 6 trials of 1 of 2 maximal (20 x 5 seconds) intermittent cycling tests with contrasting recovery periods (10 or 30 seconds). All trials were conducted on a friction-braked cycle ergometer, and fatigue scores were derived from measures of mean power output for each sprint. Apart from formula 1, which calculated fatigue from the percentage difference in mean power output between the first and last sprint, all remaining formulae produced fatigue scores that showed a reasonably good level of test-retest reliability in both intermittent test protocols (intraclass correlation range: 0.78-0.86; 95% likely range of true values: 0.54-0.97). Although between-protocol differences in the magnitude of the fatigue scores suggested good construct validity, within-protocol differences highlighted limitations with each formula. Overall, the results support the use of the percentage decrement score as the most valid and reliable measure of fatigue during brief maximal intermittent work.


Talking About Hepatitis C: FAQs From Young Adults Who Inject Drugs.
Young adults who inject drugs and live in rural communities are at high risk for hepatitis C virus (HCV) infection. Recent changes in HCV treatment must be communicated within these communities to improve access to care and reduce HCV transmission. Field workers in the ¡VÁLE! Hepatitis Treatment and Integrated Prevention Services study identified frequently asked questions (FAQs) posed by young-adult participants at high risk for HCV during screening and educational sessions. From 2016 to 2018, 183 young adults (44.3% women; 85.8% Latino/a) younger than 30 years who inject drugs and reside in Rio Arriba or Doña Ana counties in New Mexico were enrolled. The research team compiled deidentified questions during field enrollments. FAQs were reviewed and categorized into four major domains, including risk/prevention, screening, treatment, and reinfection. FAQs were addressed by a team of medical and public health professionals, using the most current research and recommendations. These FAQs address important gaps in HCV knowledge among young adults who are at high risk for infection. The FAQs also highlight the importance of risk reduction counseling provided by frontline public health providers as well as access to safe and effective HCV treatments for young adults who inject drugs.


Steroidogenic factor 1 promotes aggressive growth of castration-resistant prostate cancer cells by stimulating steroid synthesis and cell proliferation.
The dependence of prostate cancer on androgens provides a targeted means of treating advanced disease. Unfortunately, androgen deprivation therapies eventually become ineffective, leading to deadly castration-resistant prostate cancer (CRPC). One of many factors implicated in the transition to CRPC is the onset of de novo steroidogenesis. Although reactivation of steroid receptors likely plays a pivotal role in aggressive CRPC, little is understood regarding the mechanisms whereby prostate cancer cells initiate and maintain steroidogenesis. We hypothesize that steroidogenic factor 1 (SF1, NR5A1, AD4BP), a key regulator of steroidogenesis in normal endocrine tissues, is expressed in CRPC where it stimulates aberrant steroidogenesis and fuels aggressive growth. Notably, SF1 is not expressed in normal prostate tissue. Our results indicated that SF1 was absent in benign cells but present in aggressive prostate cancer cell lines. Introduction of ectopic SF1 expression in benign human prostate epithelial cells (BPH-1) stimulated increased steroidogenic enzyme expression, steroid synthesis, and cell proliferation. In contrast, data from an aggressive human prostate cancer cell line (BCaPT10) demonstrated that SF1 was required for steroid-mediated cell growth because BCaPT10 cell growth was diminished by abiraterone treatment and short hairpin RNA-mediated knockdown of SF1 (shSF1). SF1-depleted cells also exhibited defective centrosome homeostasis. Finally, whereas xenograft experiments in castrated hosts with BCaPT10 control transplants grew large, invasive tumors, BCaPT10-shSF1 knockdown transplants failed to grow. Therefore, we conclude that SF1 stimulates steroid accumulation and controls centrosome homeostasis to mediate aggressive prostate cancer cell growth within a castrate environment. These findings present a new molecular mechanism and therapeutic target for deadly CRPC.


Natural history of renal masses followed expectantly.
An increasing number of incidental renal masses have been detected with increasing use of ultrasonography, computerized tomography and magnetic resonance imaging. We investigated the natural history of incidentally detected renal masses. A total of 24 patients were included in this retrospective analysis. Average patient age was 68.3 years (range 29 to 83). The 16 males and 8 females were followed with abdominal imaging for a mean and median followup of 31.6 and 24 months, respectively (range 8 to 86). Patients elected to be observed because of age, poor medical condition or the presence of a mass in a solitary kidney. The majority of patients (22 of 24) were asymptomatic at diagnosis. Two patients were followed with bilateral renal masses, and 2 with T3b tumors. Of the 20 patients with incidental solitary renal masses, 6 were at the upper pole, 9 were mid polar and 5 lower pole. Mean maximum diameter of lesions was 3.3 cm (median 2.7, range 0.9 to 10). Growth rate was calculated based on diameter and tumor volume. Of the 24 patients only 5 demonstrated tumor growth during the surveillance period. No metastasis developed in any patients. Mean tumor growth rate observed in the 5 patients was 0.49 cm per year or 7.3 cc per year. Of the 24 patients 4 underwent surgery after surveillance because of apparent tumor growth or per patient request. Pathology revealed renal cell carcinoma in all 4. Tumor growth of renal masses is often limited. Most of our patients did not demonstrate significant growth when followed expectantly. Without tumor growth the risk of metastasis seems limited.


Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide.
Reduced expression of somatostatin receptors (SSTRs) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients. The expression of SSTRs other than SSTR2a has not been studied in large, unselected cohorts using novel rabbit monoclonal antibodies. We aimed to determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to correlate expression with clinical characteristics and the response to octreotide, and to ascertain whether preoperative octreotide treatment affected SSTR expression. The study included 78 adenomas from patients operated on consecutively during 2000 to 2010. After exclusion of 13 patients, immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65 adenomas. Twenty-eight patients received preoperative octreotide, and 37 patients were operated on without pretreatment. Twenty-six patients were randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13). SSTR expression was evaluated using a 12-grade scoring system. The responses to the octreotide test dose (GH reduction) and to 6 months of octreotide (IGF-I reduction) were measured. The majority of adenomas showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment. In a linear regression model with SSTR2a expression as the determinant, the correlation with the acute test response improved after adjustment for medical pretreatment. Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment, indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics. Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly.


Endoscopic placement of enteral feeding tubes.
Malnutrition is common in patients with acute and chronic illness. Nutritional management of these malnourished patients is an essential part of healthcare. Enteral feeding is one component of nutritional support. It is the preferred method of nutritional support in patients that are not receiving adequate oral nutrition and have a functioning gastrointestinal tract (GIT). This method of nutritional support has undergone progression over recent times. The method of placement of enteral feeding tubes has evolved due to development of new feeding tubes and endoscopic technology. Enteral feeding can be divided into methods that provide short-term and long-term access to the GIT. This review article focuses on the current range of methods of gaining access to the GIT to provide enteral feed.


Neglected diseases caused by bacterial infections.
Bacterial infections represent a major health problem, especially in third world countries. In endemic regions, large populations of people are greatly affected, but the medical care is very limited. In this review, the neglected diseases buruli ulcer and trachoma are elucidated. Buruli ulcer is caused by Mycobacterium ulcerans which produces an outstanding immunosuppressive toxin mycolactone that induces an ulcerative, necrotic skin disease. Until today, only the combination of rifampin/streptomycin is used to treat buruli ulcer. However, this therapy is ineffective and expensive. Here, we report new findings that suggest pharmaceutical formulations such as rifapentine, in combination with clarithromycin or moxifloxacin that have shown promising results in mice footpad trials. Moreover, alternative treatment options such as heat therapy, nitric oxide cremes and French clay show bactericidal effects. The genotyping of M. ulcerans also promises new ways of finding drug targets and vaccines. Trachoma, induced by the bacterium Chlamydia trachomatis, is the primary infectious cause of blindness worldwide. Recurrent infections lead to chronic inflammation of the upper tarsal conjunctiva. As a consequence, scarring and distortion of the eye lids occur, eventually resulting in blindness. First-line medications for trachoma treatment are bacteriostatic agents such as topically applied tetracylines and systematically administered azithromycin. Surgery, environmental improvements and personal hygiene are further crucial factors in controlling trachoma. Moreover, efforts are being undertaken towards the development of vaccine systems, with the major outer membrane protein and the polymorphic membrane protein acting as attractive candidates.


Neural Protein Synthesis during Aging: Effects on Plasticity and Memory.
During aging, many experience a decline in cognitive function that includes memory loss. The encoding of long-term memories depends on new protein synthesis, and this is also reduced during aging. Thus, it is possible that changes in the regulation of protein synthesis contribute to the memory impairments observed in older animals. Several lines of evidence support this hypothesis. For instance, protein synthesis is required for a longer period following learning to establish long-term memory in aged rodents. Also, under some conditions, synaptic activity or pharmacological activation can induce de novo protein synthesis and lasting changes in synaptic transmission in aged, but not young, rodents; the opposite results can be observed in other conditions. These changes in plasticity likely play a role in manifesting the altered place field properties observed in awake and behaving aged rats. The collective evidence suggests a link between memory loss and the regulation of protein synthesis in senescence. In fact, pharmaceuticals that target the signaling pathways required for induction of protein synthesis have improved memory, synaptic plasticity, and place cell properties in aged animals. We suggest that a better understanding of the mechanisms that lead to different protein expression patterns in the neural circuits that change as a function of age will enable the development of more effective therapeutic treatments for memory loss.


Interaction between hydrogen peroxide and plant hormones during germination and the early growth of pea seedlings.
Hydrogen peroxide (H(2)O(2)) increased the germination percentage of pea seeds, as well as the growth of seedlings in a concentration-dependent manner. The effect of H(2)O(2) on seedling growth was removed by incubation with 10 microm ABA. The H(2)O(2)-pretreatment produced an increase in ascorbate peroxidase (APX), peroxidase (POX) and ascorbate oxidase (AAO). The increases in these ascorbate-oxidizing enzymes correlated with the increase in the growth of the pea seedlings as well as with the decrease in the redox state of ascorbate. Moreover, the increase in APX activity was due to increases in the transcript levels of cytosolic and stromal APX (cytAPX, stAPX). The proteomic analysis showed that H(2)O(2) induced proteins related to plant signalling and development, cell elongation and division, and cell cycle control. A strong correlation between the effect of H(2)O(2) on plant growth and the decreases in ABA and zeatin riboside (ZR) was observed. The results suggest an interaction among the redox state and plant hormones, orchestrated by H(2)O(2), in the induction of proteins related to plant signalling and development during the early growth of pea seedlings.


Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies.
Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.


Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice.
Premature activation of trypsinogen activation can cause pancreatic injury and has been associated with chronic pancreatitis (CP). Mice that lack intra-acinar activation of trypsinogen, such as trypsinogen-7-null (T(-/-)) and cathepsin B-null (CB(-/-)) mice, have been used to study trypsin-independent processes of CP development. We compared histologic features and inflammatory responses of pancreatic tissues from these mice with those from wild-type mice after the development of CP. CP was induced in wild-type, T(-/-), and CB(-/-) mice by twice-weekly induction of acute pancreatitis for 10 weeks; acute pancreatitis was induced by hourly intraperitoneal injections of cerulein (50 μg/kg × 6). Pancreatic samples were collected and evaluated by histologic and immunohistochemical analyses. Normal human pancreas samples, obtained from the islet transplant program at the University of Minnesota, were used as controls and CP samples were obtained from surgical resections. Compared with pancreatic tissues from wild-type mice, those from T(-/-) and CB(-/-) mice had similar levels of atrophy, histomorphologic features of CP, and chronic inflammation. All samples had comparable intra-acinar activation of nuclear factor (NF)-κB, a transcription factor that regulates the inflammatory response, immediately after injection of cerulein. Pancreatic tissue samples from patients with CP had increased activation of NF-κB (based on nuclear translocation of p65 in acinar cells) compared with controls. Induction of CP in mice by cerulein injection does not require intra-acinar activation of trypsinogen. Pancreatic acinar cells of patients with CP have increased levels of NF-κB activation compared with controls; regulation of the inflammatory response by this transcription factor might be involved in the pathogenesis of CP.


The limitation of glycolysis in adenine-deficient Escherichia coli.
1. In many instances, there was no change in the rate of oxygen consumption per cell when adenine was withdrawn from purine auxotrophs of Escherichia coli and Salmonella typhimurium. 2. However, adenine deficiency inhibited the metabolism of glucose, mannitol or glycerol in a purA(-) strain, in purB(-) or purH(-) strains in the absence of histidine and in purB(-) mutants supplied with hypoxanthine. These are all instances where reactions occur to consume adenine nucleotides. 3. The inhibition of glucose oxidation is accompanied by the accumulation of fructose 1,6-diphosphate and dihydroxyacetone phosphate. 4. Insufficiency of ADP for phosphoglycerate kinase is the most probable cause of the inhibition.


Current treatment practices for early laryngeal carcinoma.
Controversy regarding the management of early laryngeal carcinoma persists in the absence of a definitive comparison of treatment modalities. This study examines the basic management practices for early laryngeal cancer among the American Academy of Otolaryngology-Head and Neck Surgery membership with an emphasis on the role of conservation surgery. Questionnaires were randomly distributed to 3000 members with 1000 responses. The results were collated and statistically evaluated with multivariable frequency analysis. For operable supraglottic tumors, supraglottic laryngectomy was advocated by 41.6% of those responding. Definitive radiation therapy was suggested by 5.3% of participants and total laryngectomy by 1.4%. Explanation of treatment options with the patient deciding the therapy was selected by 48.3% of responders. For suitable glottic tumors, hemilaryngectomy was recommended by 37.1%, definitive radiation therapy by 8.1%, total laryngectomy by 1.9%, and patient choice by 50.4% of members completing the survey. When patients were left to weigh the treatment options, surgery was much less likely to be chosen than if it was advocated by the physician. Trends were evident according to practice region and setting, but these variables did not correlate strongly with physician recommendations. However, date of residency completion and rating of available radiation oncology services were significant factors. The evaluation of postoperative considerations in laryngeal conservation surgery demonstrated large variability in the definition of a close margin and the perceived need for additional therapy. The varied practice patterns among the American Academy of Otolaryngology-Head and Neck Surgery membership reflect the lack of a comparative outcome analysis for the treatment of early laryngeal carcinoma. Consequently, the full reliance on patient choice, which is more pronounced among young physicians, and cost considerations may have the greatest impact on the future treatment of this disease.


Distinct roles of extracellular polymeric substances in Pseudomonas aeruginosa biofilm development.
Bacteria form surface attached biofilm communities as one of the most important survival strategies in nature. Biofilms consist of water, bacterial cells and a wide range of self-generated extracellular polymeric substances (EPS). Biofilm formation is a dynamic self-assembly process and several distinguishable stages are observed during bacterial biofilm development. Biofilm formation is shown to be coordinated by EPS production, cell migration, subpopulation differentiation and interactions. However, the ways these different factors affect each other and contribute to community structural differentiation remain largely unknown. The distinct roles of different EPS have been addressed in the present report. Both Pel and Psl polysaccharides are required for type IV pilus-independent microcolony formation in the initial stages of biofilm formation by Pseudomonas aeruginosa PAO1. Both Pel and Psl polysaccharides are also essential for subpopulation interactions and macrocolony formation in the later stages of P. aeruginosa PAO1 biofilm formation. Pel and Psl polysaccharides have different impacts on Pseudomonas quinolone signal-mediated extracellular DNA release in P. aeruginosa PAO1 biofilms. Psl polysaccharide is more important than Pel polysaccharide in P. aeruginosa PAO1 biofilm formation and antibiotic resistance. Our study thus suggests that different EPS materials play distinct roles during bacterial biofilm formation.


Mechanisms of Transmission Ratio Distortion at Hybrid Sterility Loci Within and Between Mimulus Species.
Hybrid incompatibilities are a common correlate of genomic divergence and a potentially important contributor to reproductive isolation. However, we do not yet have a detailed understanding of how hybrid incompatibility loci function and evolve within their native species, or why they are dysfunctional in hybrids. Here, we explore these issues for a well-studied, two-locus hybrid incompatibility between hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2) in the closely related yellow monkeyflower species Mimulus guttatus and M. nasutus By performing reciprocal backcrosses with introgression lines (ILs), we find evidence for gametic expression of the hms1-hms2 incompatibility. Surprisingly, however, hybrid transmission ratios at hms1 do not reflect this incompatibility, suggesting that additional mechanisms counteract the effects of gametic sterility. Indeed, our backcross experiment shows hybrid transmission bias toward M. guttatus through both pollen and ovules, an effect that is particularly strong when hms2 is homozygous for M. nasutus alleles. In contrast, we find little evidence for hms1 transmission bias in crosses within M. guttatus, providing no indication of selfish evolution at this locus. Although we do not yet have sufficient genetic resolution to determine if hybrid sterility and transmission ratio distortion (TRD) map to the same loci, our preliminary fine-mapping uncovers a genetically independent hybrid lethality system involving at least two loci linked to hms1 This fine-scale dissection of TRD at hms1 and hms2 provides insight into genomic differentiation between closely related Mimulus species and reveals multiple mechanisms of hybrid dysfunction.


Control of lung defence by mucins and macrophages: ancient defence mechanisms with modern functions.
Owing to the need to balance the requirement for efficient respiration in the face of tremendous levels of exposure to endogenous and environmental challenges, it is crucial for the lungs to maintain a sustainable defence that minimises damage caused by this exposure and the detrimental effects of inflammation to delicate gas exchange surfaces. Accordingly, epithelial and macrophage defences constitute essential first and second lines of protection that prevent the accumulation of potentially harmful agents in the lungs, and under homeostatic conditions do so effectively without inducing inflammation. Though epithelial and macrophage-mediated defences are seemingly distinct, recent data show that they are linked through their shared reliance on airway mucins, in particular the polymeric mucin MUC5B. This review highlights our understanding of novel mechanisms that link mucus and macrophage defences. We discuss the roles of phagocytosis and the effects of factors contained within mucus on phagocytosis, as well as newly identified roles for mucin glycoproteins in the direct regulation of leukocyte functions. The emergence of this nascent field of glycoimmunobiology sets forth a new paradigm for considering how homeostasis is maintained under healthy conditions and how it is restored in disease.


[Avoidance mechanisms during self stimulation].
Increased negative discordance of the dominating mode of the pressing duration histogram (PDH), which correlates with the growth of fixed bursts of stimulation is accompanied by a progressive decrease in the reinforcing properties of self-stimulation (SS), avoidance of the pedal and at the same time by a change of behavioral grooming reactions in the intervals between SS for search and consummatory reactions. Hunger considerably shortens the preferable duration of pressing or leads to the appearance of an additional mode on the PDH. With the change of the dominating PDH mode from positive discordance to a negative one, brain stimulation acquires aversive properties which are apparently due to the activation of the mechanisms of specific motivations.


Extreme nursing: a qualitative assessment of nurse retention in a remote setting.
Nurses have practiced in Bristol Bay, Alaska, since 1896. Practice opportunities are defined by institutional structures and systems; and the geography, climate, and history of remote South-west 'bush' Alaska. The Native Alaskan culture as experienced through nurses' practice, community relations, and in several cases, marriages, shapes their lives as well. The purposes of this qualitative study are three-fold: (1) to ensure the unique stories of bush Alaska nurses are preserved and told; (2) to foster a strong bush nursing tradition; and (3) to inform recruitment, hiring, and retention practices in remote settings. Ten of 14 long-term retained (>15 years) nurses still living in Bristol Bay were interviewed using a semi-structured format, based on three broad interview questions: (1) Why did you come to Bristol Bay?; (2) If you ever wanted to leave, what motivated you to stay?; and (3) What do you feel are your greatest accomplishments here? Extensive probing and dialogue was employed to develop participants' conversation. Interviews were recorded, transcribed and coded for qualitative content analysis of ideas and thematic analysis. To preserve authenticity and enhance fidelity, nurses' verbatim statements are reported at length, illustrating ideas and themes. Analysis of transcripts revealed seven ideas common to all 10 long-term retained nurse's experience in the bush: family, culture, hardship, nursing practice, fish, motivations and community. Religion or spirituality was also a common idea, but not universal. A racism code was derived to illuminate less articulated ideas from the nurses' conversation. Long-term retained bush nurses share three characteristics useful to successful recruitment and retention efforts: they have (1) a strong sense of adventure, (2) an independent outlook regarding family growth and development, and (3) a deep appreciation of Native Alaskan culture and lifestyle. In summary they advise nurses who wish to practice and stay in the bush to come with 'ample resources, mental resources, emotional, spiritual, the whole nine yards, [they] need these resources in order to survive, in order to stay here. [Also] a love for the people, not being opposite to the culture but trying to learn [from it]'. Attributes and qualities nurses bring to remote South-west bush Alaska produce a community dynamic affecting practice, health, and quality of life.


Oral Hygiene Awareness, Practices and Attitudes among Syrian Refugees in Zaatari Camp and Their Impact on Oral Health Status.
To characterise the oral hygiene habits, attitudes, and oral health practices in relation to sociodemographic factors among refugees in Jordan and to investigate their impact on the oral health status of these refugees. This cross-sectional study consisted of two parts. First, a face-to-face interview was conducted using a structured questionnaire including demographic and oral health-related questions. Second, clinical oral examination was performed using WHO criteria, DMFT and oral health indices (OHI-S). The participants were adults, aged 18 and older. All patients attending dental clinics and accompanying personnel in the waiting areas at Zaatari camp during the study period were invited to participate, with a sample size of 547 refugees (males = 212, females = 335). 547 adult refugees participated. 75.3% reported toothbrushing less than twice daily, while flossing was uncommon (9.5%). Toothbrushing habits were significantly associated with gender and smoking status. Untreated carious lesions had a high incidence (94.1%); the mean number of decayed teeth was 5.4 and was statistically significantly higher in males and smokers. The mean number of missing teeth was 3.2 and was significantly associated with males, age, smoking, and presence of chronic disease. Participants who reported conditions that had persisted 1 year or more and required ongoing medical attention or limited activities of daily living or both (e.g. diabetes mellitus, hypertension, heart diseases, thyroid disease, chronic renal disease, rheumatoid arthritis, anemia, peptic ulcer, or asthma) were recorded as having chronic disease. The mean number of filled teeth was 3.2 and was statistically significantly associated with age and presence of chronic disease. The mean DMFT was 11.8 and was statistically significantly higher in males, older people, smokers, and those with chronic disease. The OHI-S was 2.2. The most common complaint was pain (92.2%), and only 1.1% visited a dentist for a check-up. The prevalence of caries was extremely high, with poor oral hygiene practices among refugees, justifying the urgent need to develop and implement targeted oral health promotion, preventive programs and curative strategies and to enable collaboration of the oral healthcare providers and funding agencies to design the most appropriate interventions for this disadvantaged population. In addition, this information can be used as a basis upon which preventive programs can be assessed for efficacy.


Refractive errors in twin studies.
It is estimated that 1.6 billion people worldwide have myopia, a refractive error, and this number is expected to increase to approximately 2.5 billion by the year 2020. It is now well established that both the environment and genetics play a role in the development of myopia. However, the exact contribution of each of these components to myopia development has yet to be completely determined. Twin studies (classical twin model) are commonly used to determine the weighting of genetic and environmental components in disease. Over the last century, twin studies have investigated the heritability of refractive errors in different sample populations and have collectively supported a genetic basis to refractive errors. However, different sample populations and methods of data collection have produced a wide range of heritability estimates ranging from .5 to .9. This article will review those twin studies that have investigated refractive error, particularly myopia, as well as biometric measures linked to refractive error, to compare heritability estimates and methodology designs.


Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus.
Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.


Moral Distress and Moral Injury in Pharmacy and Why the Academy Needs to Care.
Pharmacists and other pharmacy personnel are experiencing job stress and burnout, and in some instances, suicidal ideation and death by suicide. However, the described lived experiences of pharmacists and other pharmacy personnel are not defined by burnout. Thus, consideration of and research about whether pharmacy personnel are possibly experiencing moral distress or moral injury is necessary and urgent. The pharmacy academy is served by considering workplace conditions and lived experiences of pharmacists because of the potential, negative impact on prospective student recruitment, quality of experiential sites and preceptors, sites for clinical faculty placement, and the well-being of alumni. Understanding phenomena occurring for pharmacy personnel and determining how they impact the pharmacy academy can lend itself to the future development of solutions.


Effect of Internal Ligand Strain on Coordination Behavior of PSP Pincer Ligands.
Chelating ligands and most specifically pincer ligands, with their characteristic co-planar binding, usually undergo deformations upon coordination, resulting in a significant ligand strain. Such an effect on the properties of the so formed complex has rarely been explored. This study is an attempt to analyze this strain and its contribution to the overall binding energy and coordination behavior of PSP pincer ligands. Hence, we designed a rigid thioxanthone-based PSP pincer ligand (I) and studied the difference in the coordination properties with the more flexible thioxanthene and thioether-based PSP pincer ligands (II and III). Although with one equivalent of Pd(II) precursor, the three ligands exhibited a similar coordination behavior leading to similar κ3-P,S,P pincer complexes, an in-depth computational analysis pointed out the different contributions of the internal strain energy in lowering the binding energy of these complexes. This effect was clearly reflected when we calculated the enthalpy change of these ligand-exchange reactions. As these exchange reactions are enthalpy-driven, these results could also be confirmed experimentally. With two equivalents of Pd(II), the three ligands diverged in their coordination behavior. Specifically, ligands I and III gave each a binuclear complex, with different coordination modes, whereas the pincer complex of ligand II remained unaffected by excess of Pd(II). Our calculations suggest that the driving force for the formation of binuclear Pd(II) complexes is the relief of the internal ligand strain. With Pt(II), only the mononuclear κ3-P,S,P pincer complexes were obtained irrespectively of the amount of the Pt(II) precursor. In these cases, we assume that kinetic inertness of the formed mononuclear pincer Pt(II) complexes prevents binding of an additional Pt(II) nucleus. This study points out the important role of the internal ligand strain in PSP pincer ligand coordination behavior. We believe that our findings can be extended to other pincer ligands systems as well.


Directionally specific paracrine communication mediated by epithelial FGF9 to stromal FGFR3 in two-compartment premalignant prostate tumors.
Tissue homeostasis in normal prostate and two-compartment nonmalignant prostate tumors depends on harmonious two-way communications between epithelial and stromal compartments. Within the fibroblast growth factor (FGF) family, signaling to an epithelial cell-specific FGF receptor (FGFR) 2IIIb-heparan sulfate complex from stromal-specific FGF7 and FGF10 delivers directionally specific instruction from stroma to epithelium without autocrine interference. Using a two-compartment transplantable prostate tumor model in which survival of stromal cells in vivo depends on epithelial cells, we show that signaling from epithelial FGF9 to stromal FGFR3 potentially mediates epithelial-to-stromal communication that also is directionally specific. FGF9 mRNA was expressed exclusively in the epithelial cells derived from well-differentiated, two-compartment Dunning R3327 rat prostate tumors. In contrast, FGFR3 was expressed at functionally significant levels only in the derived stromal cells. Competition binding and immunoprecipitation assays revealed that FGF9 only bound to an FGFR on the stromal cells. FGF9 also failed to covalently cross-link to clonal lines of stromal cells devoid of FGFR3 that expressed FGFR1 and FGFR2IIIc. Furthermore, FGF9 specifically stimulated DNA synthesis in stromal cells expressing FGFR3. These results demonstrate a directionally specific paracrine signaling from epithelial FGF9 and stromal FGFR3. Similar to the FGF7/FGF10 to FGFR2IIIb signaling from the stroma to the epithelium, the directional specificity from epithelium to stroma appears set by a combination of cell-specific expression of isoforms and cell-context specificity of FGFR isotypes for FGF.


Evaluating farm-level livestock interventions in low-income countries: a scoping review of what works, how, and why.
Livestock interventions can improve nutrition, health, and economic well-being of communities. The objectives of this review were to identify and characterize livestock interventions in developing countries and to assess their effectiveness in achieving development outcomes. A scoping review, guided by a search strategy, was conducted. Papers needed to be written in English, published in peer-reviewed journals, and describe interventions in animal health and production. Out of 2739 publications systematically screened at the title, abstract, and full publication levels, 70 met our inclusion criteria and were considered in the study. Eight relatively high-quality papers were identified and added, resulting in 78 reviewed publications. Only 15 studies used randomized controlled trial designs making it possible to confidently link interventions with the resulting outcomes. Eight studies had human nutrition or health as outcomes, 11 focused on disease control, and four were on livestock production. Eight interventions were considered successful, but only four were scalable. We found good evidence that livestock-transfer programs, leveraging livestock products for nutrition, and helping farmers manage priority diseases, can improve human well-being. Our report highlights challenges in garnering evidence for livestock interventions in developing countries and provides suggestions on how to improve the quantity and quality of future evaluations.


Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease.
Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level-dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD.


Identifying Critical Quality Metrics in Mohs Surgery: A National Expert Consensus Process.
Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.


Genetic interactions between error-prone and error-free postreplication repair pathways in Saccharomyces cerevisiae.
Evidence obtained from recent studies supports the existence of an error-free postreplication repair (PRR) and a mutagenesis pathway within the Saccharomyces cerevisiae RAD6 DNA repair group. The MMS2 gene is the only known yeast gene involved in error-free PRR that, when mutated, significantly increases the spontaneous mutation rate. In this study, the mutational spectrum of the mms2 mutator was determined and compared to the wild type strain. In addition, mutagenenic effects and genetic interactions of the mms2 mutator and rev3 anti-mutator were examined with respect to forward mutations, frameshift reversions as well as amber and ochre suppressions. It was concluded from these results that the mms2 mutator phenotype is largely dependent on the functional REV3 gene. The synergistic effects of mms2 and rev3 mutations towards killing by a variety of DNA-damaging agents ruled out the possibility that MMS2 simply acts to suppress REV3 activity and favored the hypothesis that MMS2 and REV3 form two alternative subpathways within the RAD6 DNA repair pathway. Taken together, we propose that two pathways represented by MMS2 and REV3 deal with a similar range of endogenous and environmental DNA damage but with different biological consequences, namely, error-free repair and mutagenesis, respectively.


Neutrophil Extracellular Traps and Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by an overproduction of autoantibodies. The loss of self-tolerance in SLE is believed to be caused by the dysregulation of both innate and adaptive immune systems. Neutrophils, the most abundant effector cells of innate immunity, have long been shown to be associated with SLE. However, their role in the pathogenesis of SLE was not clear until recent studies discovered abnormal regulation of neutrophil extracellular traps (NETs) in SLE patients. NETs are web-like structures composed of chromatin backbones and granular molecules. They are released by activated neutrophils through a process called "NETosis". Nets were first described in 2004 as a novel host defense mechanism to trap and kill foreign pathogens. Recent evidence shows that NETs also participate in the pathogenesis of a variety of inflammatory and autoimmune diseases, including SLE. An imbalance between NET formation and clearance in SLE patients may play a prominent role in the perpetuation of autoimmunity and the exacerbation of disease, as well as the induction of end-organ manifestations. This review summarizes the current findings regarding the contribution of NETs to the pathogenesis of SLE.


[Hybrid repair of thoracoabdominal aortic aneurysm in high-risk patients using a quadrifurcated graft].
Surgical treatment for thoracoabdominal aortic aneurysm is still challenging and is associated with a high risk of paraplegia. Hybrid repair with stent graft insertion for the thoracoabdominal aorta excluding the branches of the lumbar and visceral arteries and bypass grafting to the visceral branches has been introduced as a less invasive treatment that reduces the risk of paraplegia. For hybrid repair, it is important to have appropriate management of the revascularized grafts to the 4 visceral arteries with sufficient inflow. We have recently adopted a knitted quadrifurcated graft applied inversely from the abdominal aorta or the iliac artery to the 4 visceral arteries; the celiac, superior mesenteric, and bilateral renal arteries. To date, we have used the graft in hybrid repair of thoracoabdominal aortic aneurysm in 2 high-risk elder patients who had disseminated intravascular coagulopathy and severe renal failure, respectively. We found that a knitted quadrifurcated graft was easy to handle and useful for reducing the number of anastomoses, which were expected to shorten the operation time. Postoperative courses were uneventful without paraplegia in either patient. Postoperative computed tomography showed excellent patency of the inversely applied quadrifurcated graft without any endoleak or migration in the thoracoabdominal stent. In conclusion, revascularization of 4 visceral arteries using a quadrifurcated graft should be considered a preferable option in hybrid treatment for thoracoabdominal aortic aneurysm.


Automated Production of Human Induced Pluripotent Stem Cell-Derived Cortical and Dopaminergic Neurons with Integrated Live-Cell Monitoring.
Manual culture and differentiation protocols for human induced pluripotent stem cells (hiPSC) are difficult to standardize, show high variability and are prone to spontaneous differentiation into unwanted cell types. The methods are labor-intensive and are not easily amenable to large-scale experiments. To overcome these limitations, we developed an automated cell culture system coupled to a high-throughput imaging system and implemented protocols for maintaining multiple hiPSC lines in parallel and neuronal differentiation. We describe the automation of a short-term differentiation protocol using Neurogenin-2 (NGN2) over-expression to produce hiPSC-derived cortical neurons within 6‒8 days, and the implementation of a long-term differentiation protocol to generate hiPSC-derived midbrain dopaminergic (mDA) neurons within 65 days. Also, we applied the NGN2 approach to a small molecule-derived neural precursor cells (smNPC) transduced with GFP lentivirus and established a live-cell automated neurite outgrowth assay. We present an automated system with protocols suitable for routine hiPSC culture and differentiation into cortical and dopaminergic neurons. Our platform is suitable for long term hands-free culture and high-content/high-throughput hiPSC-based compound, RNAi and CRISPR/Cas9 screenings to identify novel disease mechanisms and drug targets.


Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study.
The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p < 0.001; women 45.9 vs 34.8 ng/ml, respectively, p = 0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio [OR] 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and gamma glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 [1.3-7.6]). Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes.


Short Communication: Accumulation of Neutral Lipids in Liver and Aorta of Nef-Transgenic Mice.
HIV-infected individuals are at high risk of developing atherosclerosis and cardiovascular disease, in part, due to HIV-induced impairment of cholesterol metabolism. In vitro studies demonstrated that HIV-1 protein Nef inhibits activity of ABCA1, the main cellular cholesterol transporter, leading to cholesterol accumulation in macrophages and conversion of these cells into foam cells, characteristic for atherosclerosis. However, the mechanisms of Nef-mediated effects on cholesterol metabolism in vivo are not well characterized. In this study, we generated Nef-transgenic mice and evaluated the accumulation of neutral lipids in liver and aorta of these animals. Nef expression was low in all transgenic mice, with some mice carrying the Nef transgene, but not expressing the Nef RNA. Using Oil Red O staining, we demonstrated increased levels of neutral lipids in liver and aorta of mice expressing Nef relative to transgenic animals, with no detectable Nef expression or control wild-type mice. These results provide direct evidence that Nef promotes cholesterol deposition in tissues.


Troubleshooting time-dependent density-functional theory for photochemical applications: oxirane.
The development of analytic-gradient methodology for excited states within conventional time-dependent density-functional theory (TDDFT) would seem to offer a relatively inexpensive alternative to better established quantum-chemical approaches for the modeling of photochemical reactions. However, even though TDDFT is formally exact, practical calculations involve the use of approximate functional, in particular the TDDFT adiabatic approximation, the use of which in photochemical applications must be further validated. Here, we investigate the prototypical case of the symmetric CC ring opening of oxirane. We demonstrate by direct comparison with the results of high-quality quantum Monte Carlo calculations that, far from being an approximation on TDDFT, the Tamm-Dancoff approximation is a practical necessity for avoiding triplet instabilities and singlet near instabilities, thus helping maintain energetically reasonable excited-state potential energy surfaces during bond breaking. Other difficulties one would encounter in modeling oxirane photodynamics are pointed out.


Association of educational achievement with pulsatile arterial diameter change of the common carotid artery: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1992.
Education is strongly inversely associated with common carotid artery intima-media thickness in the Atherosclerosis Risk in Communities (ARIC) Study. The authors extended the ARIC study of preclinical atherosclerosis by evaluating the cross-sectional association of education with common carotid artery elasticity. This study included 10,091 Black and White men and women aged 45-64 years who were free of clinical coronary heart disease and stroke/transient ischemic attack. Arterial elasticity was assessed by pulsatile arterial diameter change (PADC), derived from phase-locked echo-tracking. The smaller the PADC, the stiffer the artery. Education was categorized into grade school, high school without graduation, high school with graduation, vocational school, some college, and graduate/professional school. PADC was directly associated with educational attainment. The mean PADCs, adjusted for age, height, diastolic diameter, systolic blood pressure, pulse pressure (linear and squared), ethnicity, gender, and smoking status, in successively higher education strata were 402 (standard error (SE) 5), 403 (SE 4), 407 (SE 3), 413 (SE 4), 416 (SE 2), and 417 (SE 4) microm (p = 0.007). To the authors' knowledge, this is the first time such an association has been reported. If arterial dilation impairment precedes arterial wall thickening in the atherosclerotic process, as recent studies on endothelial dysfunction suggest, these results indicate that low socioeconomic status may be associated with early arterial pathophysiologic changes-an effect that appears to be mediated by established cardiovascular disease risk factors.


HIV status determination among tuberculosis patients from California during 2008.
Human immunodeficiency virus (HIV) infection complicates care and contributes to poor outcomes among tuberculosis (TB) patients. The Centers for Disease Control and Prevention recommends that providers test all TB patients for HIV. We assessed completeness of HIV status determination among TB patients and identified key gaps in adherence. We conducted a retrospective review of public health charts to determine the HIV status for all TB patients reported in California during 2008. We then used logistic regression to determine the factors associated with a known (positive or negative) HIV status. A random sample of TB patients was selected for secondary review to characterize the timing of HIV status determination and the providers who had opportunity to test for HIV. California TB programs. All TB patients reported from California in 2008. Proportion of patients with a known HIV status, adjusted odds ratios for having a known HIV status, proportion of patients with a known HIV status before TB diagnosis, and proportion of patients diagnosed with TB by different provider types. Only 1752 (66%) of 2667 TB patients had a known HIV status. Having a known HIV status was strongly associated with those aged between 15 and 44 years and being managed with any public provider involvement. Of 292 patients in the random sample, 12 patients (4%) had a known HIV status before TB diagnosis. Among the remaining 280 patients, 187 patients (67%) were diagnosed with TB by a private provider. The HIV status determination of TB patients was selective and not routine as recommended. Private providers can play a key role in testing for HIV at TB diagnosis. California TB programs should ensure that all TB patients have an HIV status by promulgating national recommendations, educating private providers on the benefits of testing TB patients for HIV, and monitoring completeness of HIV status determination.


Clinical analysis of 150 cases with the novel influenza A (H1N1) virus infection in Shanghai, China.
The aim of the present research was to analyze the epidemiological and clinical characteristics of the novel influenza A (H1N1) in China. We retrospectively analyzed the epidemiological information and clinical characteristics of 150 patients with the novel influenza A (H1N1) virus infection by descriptive epidemiology. There were 82 males and 68 females in this group. The median age of the 150 patients was 34.4 years (range, 4 to 77 years). There were 145 imported cases among the patients and most of these cases came from Australia, America and Canada. The main symptoms included fever, cough and sore throat. Other symptoms included: expectoration, runny nose, throat itching, sniffles, dry pharynx, headache, muscular ache, etc. CD4(+) T cell counts of 48% of the patients were lower than normal. Computed tomography (CT) of the chest in 32 cases was abnormal, including: increased bronchovascular shadows, pneumonia, pleural thickening and pleurisy, etc. Oseltamivir was the first choice for treatment of A (H1N1) influenza and it was safe and well tolerated. The symptoms were minor and the prognosis was good. All patients recovered fully after treatment. Considering the fact that the flu is highly infectious and can be carried through human to human contact rapidly, local Centers for Disease Control and prevention (CDC) should strengthen monitoring and take some measures in view of an influenza A (H1N1) onslaught.


[Why to audit to research ethics committees?].
Ethics committees in biomedical research have the responsibility to ensure the protection of human participants in the studies. In order to improve the quality of their work they must undergo audit procedures commissioned by the sponsors and inspections done by the regulatory authorities. Through these procedures, improvement of their functions should be guaranteed, so they can optimize their tasks and accomplish in the best way the purpose for which they were created.


Boric Acid-Functionalized Carbon Dots as a High-Performance Antibacterial Agent against Escherichia coli.
Bacterial infections and antibiotic abuse are a global threat to human health. In recent years, there has been a boom in research on antimicrobial agents with low toxicity and efficient nanomaterials. Boric acid-functionalized carbon dots (B-CDs) with negative surface charge were synthesized by the hydrothermal method. Covalent bonds were formed between the boric acid groups and the cis-diol groups of the polysaccharide in the bacterial cell wall, and numerous B-CDs were trapped on the bacterial surface. In the experiments of antibacterial activity, B-CDs presented strong bactericidal activity against Escherichia coli (E. coli) with a minimum bactericidal concentration of 12.5 μg/mL. The antibacterial mechanism suggested that B-CDs entered the cell interior by diffusion and posed significant damage to the double helix structure of E. coli DNA. Furthermore, B-CDs exhibited low toxicity. The results demonstrated that the novel antimicrobial B-CDs not only fought against E. coli infection and antibiotic misuse but also provided new ideas for safe and effective antimicrobial agents of carbon nanomaterials.


Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience.
Hydroxychloroquine and Ivermectin are advocated as potential treatments for coronavirus disease 2019 (COVID-19) despite the lack of supportive clinical evidence. In this study, outcomes associated with Hydroxychloroquine and/or Ivermectin were determined in a series of patients with confirmed COVID-19 from a single institution in Brazil. Consecutive patients admitted between March and July 2020 were retrospectively analyzed and divided into four treatment categories: no treatment (Group 0), Ivermectin only (Group I), Hydroxychloroquine only (Group II), and Hydroxychloroquine and Ivermectin (Group III). Intensive care unit admission, mechanical ventilation, and death were compared between the Groups. A total of 230 patients were included, with the following treatment distribution: 35.2% (0), 9.1% (I), 48.3% (II), and 7.4% (III). Groups I, II, and III had the higher rates of Intensive care unit admission, mechanical ventilation, or death (0: 23.5% versus I: 38.1% versus II: 37.8% versus III: 70.6%, p=0.002), and the greatest mortality was found in Group III (0 versus III: 13.6% versus 35.3%, p=0.03). In the multivariate analysis, Hydroxychloroquine remained significantly associated with death (OR 3.3, 95%CI 1.1-9.6, p=0.03). In a series of consecutive hospitalized patients with COVID-19, Ivermectin was not associated with improved outcomes and Hydroxychloroquine may have resulted in a harmful effect.


Management of acute chest pain syndrome.
In differentiating the various etiologies of acute chest pain syndromes, the clinician is faced with identifying life-threatening situations. This article has presented a diagnostic approach for establishing the cardiovascular and noncardiovascular etiologies of acute chest pain syndromes. Cardiovascular etiologies must be identified early upon presentation in order to minimize morbidity and mortality. Myocardial ischemia and particularly necrosis is time dependent: early intervention preserves myocardium, particularly when initiating thrombolytic therapy. Aortic valvular disease, particularly critical aortic stenosis, if unrecognized, can precipitate rapid patient deterioration if inappropriately treated with nitrate therapy for presumed ischemic disease. Aortic dissection, if not properly diagnosed, can progress to stroke, MI, paralysis, and death. Noncardiovascular etiologies are similarly complex but often have less potential for life-threatening consequences. In identifying gastrointestinal bleeding, a careful rectal exam may be safely performed even in the setting of MI. A tension pneumothorax can suddenly compromise vascular return and progress to sudden death if unrecognized. Finally, chest wall symptoms, though seldom life-threatening, can be debilitating to the patient and often respond to anti-inflammatory therapy. In conclusion, the goals of this article were to present a step-wise approach to the diagnosis and management of an often complex presentation. By systematically approaching these patients with a thorough understanding of etiologies, diagnostic options, and therapeutic considerations, both physician anxiety as well as patient complications will be greatly diminished.