Methanogen Diversity in Indigenous and Introduced Ruminant Species on the Tibetan Plateau.
Host factors are regarded as important in shaping the archaeal community in the rumen but few controlled studies have been performed to demonstrate this across host species under the same environmental conditions. A study was designed to investigate the structure of the methanogen community in the rumen of two indigenous (yak and Tibetan sheep) and two introduced domestic ruminant (cattle and crossbred sheep) species raised and fed under similar conditions on the high altitude Tibetan Plateau. The methylotrophic Methanomassiliicoccaceae was the predominant archaeal group in all animals even though Methanobrevibacter are usually present in greater abundance in ruminants globally. Furthermore, within the Methanomassiliicoccaceae family members from Mmc. group 10 and Mmc. group 4 were dominant in Tibetan Plateau ruminants compared to Mmc. group 12 found to be highest in other ruminants studied. Small ruminants presented the highest number of sequences that belonged to Methanomassiliicoccaceae compared to the larger ruminants. Although the methanogen community structure was different among the ruminant species, there were striking similarities between the animals in this environment. This indicates that factors such as the extreme environmental conditions and diet on the Tibetan Plateau might have a greater impact on rumen methanogen community compared to host differences.


Dynamical Quantum Phase Transitions: A Geometric Picture.
The Loschmidt echo is a purely quantum-mechanical quantity whose determination for large quantum many-body systems requires an exceptionally precise knowledge of all eigenstates and eigenenergies. One might therefore be tempted to dismiss the applicability of any approximations to the underlying time evolution as hopeless. However, using the fully connected transverse-field Ising model as an example, we show that this indeed is not the case and that a simple semiclassical approximation to systems well described by mean-field theory is, in fact, in good quantitative agreement with the exact quantum-mechanical calculation. Beyond the potential to capture the entire dynamical phase diagram of these models, the method presented here also allows for an intuitive geometric interpretation of the fidelity return rate at any temperature, thereby connecting the order parameter dynamics and the Loschmidt echo in a common framework. Videos of the postquench dynamics provided in Supplemental Material visualize this new point of view.


Comparison of choroidal thickness using swept-source and spectral-domain optical coherence tomography in normal Indian eyes.
Choroidal thickness measurements are reported to differ between spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT). The aim of this study was to assess the comparability of choroidal thickness measurements using SS-OCT and SD-OCT devices among normal participants. This was a prospective study of 31 (62 eyes) normal participants. Choroidal imaging was performed sequentially with the Spectralis OCT (SD-OCT) and the deep range imaging OCT (DRI OCT-1) (SS-OCT) using standardized imaging protocols. The subfoveal choroidal thickness (SFChT) was measured manually by two masked retinal specialists. Paired t-tests and intraclass correlation coefficients (ICCs) were used to compare the measurements. The mean SFChT was 319.5 μm and 325.3 μm for DRI OCT-1 and Spectralis OCT, respectively (P = 0.001), with a mean difference of 5.9 with ICC of 0.97. The mean difference in choroidal thickness between the OCT devices was larger among eyes with choroidal thickness > 350 μm compared with eyes with thinner choroids (8.0 μm vs. 4.7 μm). SFChT measurements are comparable between DRI OCT-1 and Spectralis OCT. The variability between the devices increases in thicker choroids.


[Treatment decision for periodontal patients with history of cancer].
Radiotherapy and chemotherapy might change the healing process of periodontal disease by reducing there storability of the periodontal tissues, leading the increase of attachment lose and alveolar bone absorption. The primary periodontal lesions could be aggravated. Therefore, oral screening should be conducted before periodontal treatment, in order to eliminate dental focal infection, to stabilize the oral environment and to prevent and reduce complications after cancer treatment. The patient's general situation should be evaluated before the periodontal treatment too, so as to ensure the patient could tolerate the radiotherapy and chemotherapy in the short interval between diagnosis and treatment of cancer. The periodontal treatment should be more conservative than normal periodontal patients. The indication for tooth extraction in these patients should be less conservative.


Single-particle analysis reveals shutoff control of the Arabidopsis ammonium transporter AMT1;3 by clustering and internalization.
Ammonium is a preferred source of nitrogen for plants but is toxic at high levels. Plant ammonium transporters (AMTs) play an essential role in NH4(+) uptake, but the mechanism by which AMTs are regulated remains unclear. To study how AMTs are regulated in the presence of ammonium, we used variable-angle total internal reflection fluorescence microscopy and fluorescence cross-correlation spectroscopy for single-particle fluorescence imaging of EGFP-tagged AMT1;3 on the plasma membrane of Arabidopsis root cells at various ammonium levels. We demonstrated that AMT1;3-EGFP dynamically appeared and disappeared on the plasma membrane as moving fluorescent spots in low oligomeric states under N-deprived and N-sufficient conditions. Under external high-ammonium stress, however, AMT1;3-EGFPs were found to amass into clusters, which were then internalized into the cytoplasm. A similar phenomenon also occurred in the glutamine synthetase mutant gln1;2 background. Single-particle analysis of AMT1;3-EGFPs in the clathrin heavy chain 2 mutant (chc2 mutant) and Flotllin1 artificial microRNA (Flot1 amiRNA) backgrounds, together with chemical inhibitor treatments, demonstrated that the endocytosis of AMT1;3 clusters induced by high-ammonium stress could occur mainly through clathrin-mediated endocytic pathways, but the contribution of microdomain-associated endocytic pathway cannot be excluded in the internalization. Our results revealed that the clustering and endocytosis of AMT1;3 provides an effective mechanism by which plant cells can avoid accumulation of toxic levels of ammonium by eliminating active AMT1;3 from the plasma membrane.


Temporal and spatial properties of the pattern-reversal VEPs in infants below 2 months of age.
Pattern VEP measurements in infants below 2 months of age do not seem to show appreciable developmental changes in contrast sensitivity and cut-off spatial frequency in spite of the marked structural maturation that takes place in the visual system. This paper investigates the temporal parameters of the pattern VEP in order to establish electrophysiological criteria in detecting developmental changes of the visual pathway in this age range. In comparison with the adult, the neonatal response latency is delayed about 155 ms. The delay shortens during the first two months with a slope of around 1 ms/day. The neonatal temporal and spatial tuning functions, as compared with the adult ones, are markedly shifted towards lower temporal and spatial frequencies respectively, and do not show measurable changes in the early post-natal period.


Discovery of a Potent and Selective CCR4 Antagonist That Inhibits Treg Trafficking into the Tumor Microenvironment.
Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the CC chemokine ligands CCL17 and CCL22. In some cancers, Treg accumulation correlates with poor patient prognosis. Preclinical data suggests that preventing the recruitment of Treg and increasing the population of activated effector T cells (Teff) in the TME can potentiate antitumor immune responses. We developed a novel series of potent, orally bioavailable small molecule antagonists of CCR4. From this series, several compounds exhibited high potency in distinct functional assays in addition to good in vitro and in vivo ADME properties. The design, synthesis, and SAR of this series and confirmation of its in vivo activity are reported.


Advances in prodrug design for Parkinson's disease.
Parkinson's Disease (PD) is a neurodegenerative disorder of the central nervous system (CNS) characterized by motor dysfunctions, such as bradykinesia, rigidity, neuropsychiatric symptoms, and others. The pharmacological treatment of the disease is only symptomatic since, to date, there is no treatment to stop or slow PD. Currently, L-Dopa (LD) remains the gold standard therapy even though it undergoes peripheral metabolism causing several side effects, such as nausea, vomiting and orthostatic hypotension. Areas covered: This review is focused on recent developments in strategies involving prodrugs to enhance DA and/or LD absorption, their chemical and enzymatic stabilities, and selective targeting to the central nervous system. Expert opinion: The prodrug strategy remains one of the most promising approaches to improve pharmaceutical, pharmacokinetic, and pharmacodynamic properties of hydrophilic compounds, such as anti-Parkinson drugs (DA and LD). Prodrugs developed in recent years have demonstrated good pharmacokinetic profiles, affording a sustained release of LD and reducing its plasma level fluctuations. The development of new prodrugs that may reach the BBB unaltered and with a good ADME (Absorption, Distribution, Metabolism, Elimination) profile and pharmacological efficacy represents an exciting challenge for medicinal chemists.


Efficient modulation of cellular phosphorus components in response to phosphorus deficiency in the dinoflagellate Karenia mikimotoi.
Dinoflagellates are the most common phytoplankton group and account for more than 75% of harmful algal blooms in coastal waters. In recent decades, dinoflagellates seem to prevail in phosphate-depleted waters. However, the underlying acclimation mechanisms and competitive strategies of dinoflagellates in response to phosphorus deficiency are poorly understood, especially in terms of intracellular phosphorus modulation and recycling. Here, we focused on the response of intracellular phosphorus metabolism to phosphorus deficiency in the model dinoflagellate Karenia mikimotoi. Our work reveals the strong capability of K. mikimotoi to efficiently regulate intracellular phosphorus resources, particularly through membrane phospholipid remodeling and miRNA regulation of energy metabolism. Our research improved the understanding of intracellular phosphorus metabolism in marine phytoplankton and underscored the advantageous strategies of dinoflagellates in the efficient modulation of internal phosphorus resources to maintain active physiological activity and growth under unsuitable phosphorus conditions, which help them outcompete other species in coastal phosphate-depleted environments.


Comparative salivary proteome of hepatitis B- and C-infected patients.
Hepatitis B and C virus (HBV and HCV) infections are an important cause of cirrhosis and hepatocellular carcinoma. The natural history has a prominent latent phase, and infected patients may remain undiagnosed; this situation may lead to the continuing spread of these infections in the community. Compelling reasons exist for using saliva as a diagnostic fluid because it meets the demands of being an inexpensive, noninvasive and easy-to-use diagnostic method. Indeed, comparative analysis of the salivary proteome using mass spectrometry is a promising new strategy for identifying biomarkers. Our goal is to apply an Orbitrap-based quantitative approach to explore the salivary proteome profile in HBV- and HCV-infected patients. In the present study, whole saliva was obtained from 20 healthy, (control) 20 HBV-infected and 20 HCV-infected subjects. Two distinct pools containing saliva from 10 subjects of each group were obtained. The samples were ultracentrifuged and fractionated, and all fractions were hydrolyzed (trypsin) and injected into an LTQ-VELOS ORBITRAP. The identification and analyses of peptides were performed using Proteome Discoverer1.3 and ScaffoldQ + v.3.3.1. From a total of 362 distinct proteins identified, 344 proteins were identified in the HBV, 326 in the HCV and 303 in the control groups. Some blood proteins, such as flavin reductase (which converts biliverdin to bilirubin), were detected only in the HCV group. The data showed a reduced presence of complement C3, ceruloplasmin, alpha(1)-acid glycoprotein and alpha(2)-acid glycoprotein in the hepatitis-infected patients. Peptides of serotransferrin and haptoglobin were less detected in the HCV group. This study provides an integrated perspective of the salivary proteome, which should be further explored in future studies targeting specific disease markers for HBV and HCV infection.


Fracture resistance of weakened teeth restored using accessory glass fiber posts.
This study used differential root weakening to evaluate the fracture resistance of bovine teeth restored using glass fiber posts (with or without accessory glass fiber posts). Fifty bovine mandibular incisors were sectioned 14 mm from the apex, fixed in acrylic resin blocks, and divided into 5 groups: healthy roots with a glass fiber post (Group 1), partially weakened teeth with a glass fiber post (Group 2), partially weakened teeth with a glass fiber post and 2 accessory glass fiber posts (Group 3), extensively weakened teeth with a glass fiber post (Group 4), and extensively weakened teeth with a glass fiber post and 5 accessory glass fiber posts (Group 5). Posts were luted with resin cement, cores were prepared using composite resin, and metallic crowns were cemented. The specimens were stored in distilled water at 37°C for more than 72 hours until the fracture resistance test. Specimens were loaded at 135 degrees relative to the long axis of the tooth at a crosshead speed of 0.5 mm/minute in a universal testing machine. All groups predominantly exhibited favorable failure patterns and there were no statistically significant differences between groups (two-way ANOVA, α = 0.05).


Engineering Ion Diffusion by CoS@SnS Heterojunction for Ultrahigh-Rate and Stable Potassium Batteries.
Transitional metal sulfides (TMSs) are considered as promising anode candidates for potassium storage because of their ultrahigh theoretical capacity and low cost. However, TMSs suffer from low electronic, ionic conductivity and significant volume expansion during potassium ion intercalation. Here, we construct a carbon-coated CoS@SnS heterojunction which effectively alleviates the volume change and improves the electrochemical performance of TMSs. The mechanism analysis and density functional theory (DFT) calculation prove the acceleration of K-ion diffusion by the built-in electric field in the CoS@SnS heterojunction. Specifically, the as-prepared material maintains 81% of its original capacity after 2000 cycles at 500 mA g-1. In addition, when the current density is set at 2000 mA g-1, it can still deliver a high discharge capacity of 210 mAh g-1. Moreover, the full cell can deliver a high capacity of 400 mAh g-1 even after 150 cycles when paired with a perylene-3,4,9,10-tetracarboxydiimide (PTCDI) cathode. This work is expected to provide a material design idea dealing with the unstable and low rate capability problems of potassium-ion batteries.


Modulation of the sensitivity of FimB recombination to branched-chain amino acids and alanine in Escherichia coli K-12.
Phase variation of type 1 fimbriae of Escherichia coli requires the site-specific recombination of a short invertible element. Inversion is catalyzed by FimB (switching in either direction) or FimE (inversion mainly from on to off) and is influenced by auxiliary factors integration host factor (IHF) and leucine-responsive regulatory protein (Lrp). These proteins bind to sites (IHF site II and Lrp sites 1 and 2) within the invertible element to stimulate recombination, presumably by bending the DNA to enhance synapses. Interaction of Lrp with a third site (site 3) cooperatively with sites 1 and 2 (termed complex 1) impedes recombination. Inversion is stimulated by the branched-chain amino acids (particularly leucine) and alanine, and according to a current model, the amino acids promote the selective loss of Lrp from site 3 (complex 2). Here we show that the central portion of the fim invertible element, situated between Lrp site 3 and IHF site II, is dispensable for FimB recombination but that this region is also required for full amino acid stimulation of inversion. Further work reveals that the region is likely to contain multiple regulatory elements. Lrp site 3 is shown to bind the regulatory protein with low affinity, and a mutation that enhances binding to this element is found both to diminish the stimulatory effects of IVLA on FimB recombination and to inhibit recombination in the absence of the amino acids. The results obtained emphasize the importance of Lrp site 3 as a control element but also highlight the complexity of the regulatory system that affects this site.


Mutations in the 'DRY' motif of the CB1 cannabinoid receptor result in biased receptor variants.
The role of the highly conserved 'DRY' motif in the signaling of the CB1 cannabinoid receptor (CB1R) was investigated by inducing single-, double-, and triple-alanine mutations into this site of the receptor. We found that the CB1R-R3.50A mutant displays a partial decrease in its ability to activate heterotrimeric Go proteins (∼80% of WT CB1R (CB1R-WT)). Moreover, this mutant showed an enhanced basal β-arrestin2 (β-arr2) recruitment. More strikingly, the double-mutant CB1R-D3.49A/R3.50A was biased toward β-arrs, as it gained a robustly increased β-arr1 and β-arr2 recruitment ability compared with the WT receptor, while its G-protein activation was decreased. In contrast, the double-mutant CB1R-R3.50A/Y3.51A proved to be G-protein-biased, as it was practically unable to recruit β-arrs in response to agonist stimulus, while still activating G-proteins, although at a reduced level (∼70% of CB1R-WT). Agonist-induced ERK1/2 activation of the CB1R mutants showed a good correlation with their β-arr recruitment ability but not with their G-protein activation or inhibition of cAMP accumulation. Our results suggest that G-protein activation and β-arr binding of the CB1R are mediated by distinct receptor conformations, and the conserved 'DRY' motif plays different roles in the stabilization of these conformations, thus mediating both G-protein- and β-arr-mediated functions of CB1R.


Envelope method with ignorable missing data.
Envelope method was recently proposed as a method to reduce the dimension of responses in multivariate regressions. However, when there exists missing data, the envelope method using the complete case observations may lead to biased and inefficient results. In this paper, we generalize the envelope estimation when the predictors and/or the responses are missing at random. Specifically, we incorporate the envelope structure in the expectation-maximization (EM) algorithm. As the parameters under the envelope method are not pointwise identifiable, the EM algorithm for the envelope method was not straightforward and requires a special decomposition. Our method is guaranteed to be more efficient, or at least as efficient as, the standard EM algorithm. Moreover, our method has the potential to outperform the full data MLE. We give asymptotic properties of our method under both normal and non-normal cases. The efficiency gain over the standard EM is confirmed in simulation studies and in an application to the Chronic Renal Insufficiency Cohort (CRIC) study.


[Epidemiological study of human type 5 adenovirus in Guangzhou using chemiluminescence for neutralizing antibody assay].
To establish a high-throughput chemiluminescence assay of serotype 5 specific neutralizing antibody and understand the epidemiology of this antibody in the healthy adults and children in Guangzhou. Using rAd5 carrying the reporter gene of secreted alkaline phosphatases (SEAP), serum samples from 116 healthy adults and 94 healthy children were examined with chemiluminescence assay to detect the presence of Ad5 neutralizing antibody. The reliability of this assay was tested against conventional cytopathic effect observation. The chemiluminescence assay using secreted alkaline phosphatases (SEAP) as the reporter allowed rapid, sensitive, specific and reproducible detection of serotype 5 specific neutralizing antibody for epidemiological study of Ad5, which was positive in 26.72% of the adults and 17.02% of the children in this study. Ad5 neutralizing antibody is prevalent in the population of Guangzhou, suggesting the necessity of developing other serotype adenovectors for better vaccination and therapeutic effects.


Responses of Rapid Viscoanalyzer Profile and Other Rice Grain Qualities to Exogenously Applied Plant Growth Regulators under High Day and High Night Temperatures.
High-temperature stress degrades the grain quality of rice; nevertheless, the exogenous application of plant growth regulators (PGRs) might alleviate the negative effects of high temperatures. In the present study, we investigated the responses of rice grain quality to exogenously applied PGRs under high day temperatures (HDT) and high night temperatures (HNT) under controlled conditions. Four different combinations of ascorbic acid (Vc), alpha-tocopherol (Ve), brassinosteroids (Br), methyl jasmonates (MeJA) and triazoles (Tr) were exogenously applied to two rice cultivars (IR-64 and Huanghuazhan) prior to the high-temperature treatment. A Nothing applied Control (NAC) was included for comparison. The results demonstrated that high-temperature stress was detrimental for grain appearance and milling qualities and that both HDT and HNT reduced the grain length, grain width, grain area, head rice percentage and milled rice percentage but increased the chalkiness percentage and percent area of endosperm chalkiness in both cultivars compared with ambient temperature (AT). Significantly higher grain breakdown, set back, consistence viscosity and gelatinization temperature, and significantly lower peak, trough and final viscosities were observed under high-temperature stress compared with AT. Thus, HNT was more devastating for grain quality than HDT. The exogenous application of PGRs ameliorated the adverse effects of high temperature in both rice cultivars, and Vc+Ve+MejA+Br was the best combination for both cultivars under high temperature stress.


Propylthiouracil-induced antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis in a patient with a predisposition to autoimmune abnormalities.
Abstract A 65-year-old woman with a history of primary biliary cirrhosis was diagnosed as having myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated crescentic glomerulonephritis (GN) during propylthiouracil (PTU) therapy for Graves' disease. Antinuclear antibodies, as well as various thyroid-associated autoantibodies, had been detected since the diagnosis of Graves' disease was made. The patient carried human leukocyte antigens (HLAs) DR4 and DR9, the two HLA haplotypes that have been reported to be related to ANCA-associated vasculitis. Withdrawal of PTU and the administration of prednisolone resulted in a decrease in the titer of MPO-ANCA, together with an improvement in renal function. It is suggested that in addition to the PTU therapy, her genetic predisposition to autoimmunity had played a role in the production of MPO-ANCA and the development of crescentic GN.


The impact of contextual information on decision-making in footwear examination: An eye-tracking study.
In order to investigate whether context factors and expectations might potentially influence the decision-making of forensic footwear examiners, we collected the gaze process of experts examining the shoeprint image sets through the eye-tracking recorder. Additional to eye movement data as an objective measure, questionnaires were completed, and survey was conducted afterwards. Twenty-three qualified examiners assessed the similarity among shoe images for 22 different cases, including three sets were laterally reversed. We divided the experiment into two sessions, and then compared the examiners' performance with and without contextual information. The results showed the effects of contextual bias manipulate on both behavioral data and eye tracking data. The consensus and accuracy of examiners with contextual information were higher than those without contextual information. In the eye-tracking data, there is a significant difference between fixation counts and saccadic counts under contextual information. In addition, we found that the contextual information produced significant changes in inter-examiner consistency as measured by the Earth Mover Distance metric. However, there is no significant statistic differences in saccadic amplitude and total fixation duration of the examiners after exposure to contextual information. Our research results are instructive for understanding the cognitive process of shoeprint examination involved in real cases. In this process, stimuli related to context factors may affect decision-making and behavior. Implications for contextual effect causes are discussed.


Role of apoptosis in mediating diclofenac-induced teratogenesis: An in vitro approach.
Diclofenac (DCF) is among the most commonly used nonsteroidal anti-inflammatory drugs worldwide for the treatment of various conditions in postpubertal women. However, very limited information is available regarding its safety during pregnancy and teratogenecity. The present study was designed to elucidate the effects of DCF on the developing rat embryos during the major organogenesis period and investigate the critical role of apoptosis in bringing about these congenital anomalies. Embryos were exposed in vitro to various concentrations of DCF, that is, 0, 3.75, 7.5 and 15 µg/ml for 24 h, respectively, and examined for the growth and differentiation at the end of the culture period for the presence of any specific malformations. Growth and developmental parameters such as weight of embryos, crown-rump length and number of somites were found to be lower in the embryos exposed to high concentrations of DCF (7.5 and 15.0 μg/ml) when compared with the untreated control. However, no significant difference in growth parameters was found between embryos exposed to 3.75 µg/ml and the control group. In parallel to this, flow cytometric analysis and DNA quantitation of cultured rat embryos were performed to verify the involvement of apoptosis in mediating DCF-induced teratogenesis. A concentration-dependent increase in apoptosis in embryos suggests a possible engagement of apoptosis in the role of DCF as a teratogenic agent. A detailed analysis of the actual effect of DCF on cellular apoptotic machinery necessitates further evaluation.


Flavanols from evening primrose (Oenothera paradoxa) defatted seeds inhibit prostate cells invasiveness and cause changes in Bcl-2/Bax mRNA ratio.
In this study, we assessed the influence of an evening primrose flavanol preparation (EPFP) on proliferation and invasiveness of human prostate cancer cells (DU 145) and immortalized prostate epithelial cells (PNT1A). We report for the first time that EPFP reduces DU 145 cell proliferation (IC50 = 97 μM GAE for 72 h incubation) and invasiveness (by 24% versus control at 75 μM GAE). EPFP strongly inhibited PNT1A invasiveness in a concentration-dependent manner (by 67% versus control at 75 μM GAE) and did not cause a reduction in their proliferation. Furthermore, EPFP inhibited the activities of MMP-2 and MMP-9 secreted to culture medium by PNT1A cells by 84% and 34% versus control at 100 μM GAE, respectively. In the case of DU 145, MMP-9 activity at 100 μM GAE was reduced by 37% versus control. Moreover, the evening primrose seed flavanols suppressed the expression of selected genes (MMP-1, MMP-9, MMP-14, c-Fos, c-Jun, and VEGF) and also caused favorable changes in Bcl-2/Bax mRNA ratio which render DU 145 cells more sensitive to apoptosis-triggering agents. An additional confirmation of the proapoptotic activity of EPFP toward DU 145 was visualization of characteristic apoptotic bodies by DAPI staining. In conclusion, this study suggests that EPFP may increase apoptosis and reduce angiogenesis of prostate cancer cells.


Mediator Engineering of Saccharomyces cerevisiae To Improve Multidimensional Stress Tolerance.
Saccharomyces cerevisiae is a well-performing workhorse in chemical production, which encounters complex environmental stresses during industrial processes. We constructed a multiple stress tolerance mutant, Med15V76R/R84K, that was obtained by engineering the KIX domain of Mediator tail subunit Med15. Med15V76R/R84K interacted with transcription factor Hap5 to improve ARV1 expression for sterol homeostasis for decreasing membrane fluidity and thereby enhancing acid tolerance. Med15V76R/R84K interacted with transcription factor Mga2 to improve GIT1 expression for phospholipid biosynthesis for increasing membrane integrity and thereby improving oxidative tolerance. Med15V76R/R84K interacted with transcription factor Aft1 to improve NFT1 expression for inorganic ion transport for reducing membrane permeability and thereby enhancing osmotic tolerance. Based on this Med15 mutation, Med15V76R/R84K, the engineered S. cerevisiae strain, showed a 28.1% increase in pyruvate production in a 1.0-L bioreactor compared to that of S. cerevisiae with its native Med15. These results indicated that Mediator engineering provides a potential alternative for improving multidimensional stress tolerance in S. cerevisiae. IMPORTANCE This study identified the role of the KIX domain of Mediator tail subunit Med15 in response to acetic acid, H2O2, and NaCl in S. cerevisiae. Engineered KIX domain by protein engineering, the mutant strain Med15V76R/R84K, increased multidimensional stress tolerance and pyruvate production compared with that of S. cerevisiae with its native Med15. The Med15V76R/R84K could increase membrane related genes expression possibly by enhancing interaction with transcription factor to improve membrane physiological functions under stress conditions.


Survey of experiences with the mandibular staple bone plate.
The mandibular staple bone plate has been used to reconstruct the atrophic or deformed mandible in more than 400 cases. A survey was undertaken to evaluate those cases; results indicate that 90% of patients have satisfactory function.


47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling.
Cytogenetic surveys of neonates have found that approximately one boy in 500 is born with an extra sex chromosome. Some of these boys are now being diagnosed when prenatal karyotyping is done for the detection of Down syndrome and other major aneuploidies. This study estimates what proportion of those not detected prenatally will be diagnosed postnatally and what the indications for karyotyping are likely to be. We ascertained all 47,XXY and 47,XYY males detected prenatally and postnatally (during the 4 years 1990-1993) in the three cytogenetic laboratories in the North Thames (West) region. The age at diagnosis and indication for karyotyping were noted for cases diagnosed postnatally. Less than 10 per cent of the estimated number of affected fetuses were detected prenatally. This study suggests that most males born with these chromosome patterns will go through life without being karyotyped, that the commonest indication for a 47,XYY male to be karyotyped will be developmental delay and/or behaviour problems, and that the commonest indication for a Klinefelter male to be karyotyped will be hypogonadism and/or infertility. It would appear that most undiagnosed 47,XXY and 47,XYY males do not look or behave in a manner which prompts testing for a chromosome abnormality.


Nanobodies as novel therapeutic agents in envenomation.
An effective therapy against envenoming should be a priority in view of the high number scorpion stings and snakebites. Serum therapy is still widely applied to treat the envenomation victims; however this approach suffers from several shortcomings. The employment of monoclonal antibodies might be an outcome as these molecules are at the core of a variety of applications from protein structure determination to cancer treatment. The progress of activities in the twilight zone between genetic and antibody engineering have led to the development of a unique class of antibody fragments. These molecules possess several benefits and lack many possible disadvantages over classical antibodies. Within recombinant antibody formats, nanobodies or single domain antigen binding fragments derived from heavy chain only antibodies in camelids occupy a privileged position. In this paper we will briefly review the common methods of envenomation treatment and focus on details of various in vivo research activities that investigate the performance of recombinant, monoclonal nanobodies in venom neutralization. Nanobodies bind to their cognate target with high specificity and affinity, they can be produced in large quantities from microbial expression systems and are very robust even when challenged with harsh environmental conditions. Upon administering, they rapidly distribute throughout the body and seem to be well tolerated in humans posing low immunogenicity. Scorpion and snake envenomation is a major issue in developing countries and nanobodies as a venom-neutralizing agent can be considered as a valuable and promising candidate in envenomation therapy.


Integration of photoperiod and cold temperature signals into flowering genetic pathways in Arabidopsis.
Appropriate timing of flowering is critical for propagation and reproductive success in plants. Therefore, flowering time is coordinately regulated by endogenous developmental programs and external signals, such as changes in photoperiod and temperature. Flowering is delayed by a transient shift to cold temperatures that frequently occurs during early spring in the temperate zones. It is known that the delayed flowering by short-term cold stress is mediated primarily by the floral repressor FLOWERING LOCUS C (FLC). However, how the FLC-mediated cold signals are integrated into flowering genetic pathways is not fully understood. We have recently reported that the INDUCER OF CBF EXPRESSION 1 (ICE1), which is a master regulator of cold responses, FLC, and the floral integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) constitute an elaborated feedforward-feedback loop that integrates photoperiod and cold temperature signals to regulate seasonal flowering in Arabidopsis. Cold temperatures promote the binding of ICE1 to FLC promoter to induce its expression, resulting in delayed flowering. However, under floral inductive conditions, SOC1 induces flowering by blocking the ICE1 activity. We propose that the ICE1-FLC-SOC1 signaling network fine-tunes the timing of photoperiodic flowering during changing seasons.


Dielectric and Piezoelectric Properties of PZT Composite Thick Films with Variable Solution to Powder Ratios.
The use of PZT films in sliver-mode high-frequency ultrasonic transducers applications requires thick, dense, and crack-free films with excellent piezoelectric and dielectric properties. In this work, PZT composite solutions were used to deposit PZT films >10 μm in thickness. It was found that the functional properties depend strongly on the mass ratio of PZT sol-gel solution to PZT powder in the composite solution. Both the remanent polarization, P(r), and transverse piezoelectric coefficient, e(31,) (f), increase with increasing proportion of the sol-gel solution in the precursor. Films prepared using a solution-to-powder mass ratio of 0.5 have a remanent polarization of 8 μC/cm(2), a dielectric constant of 450 (at 1 kHz), and e(31,) (f) = -2.8 C/m(2). Increasing the solution-to-powder mass ratio to 6, the films were found to have remanent polarizations as large as 37 μC/cm(2), a dielectric constant of 1250 (at 1 kHz) and e(31,) (f) = -5.8 C/m(2).


Long-Lived and Thermoresponsive Emulsion Foams Stabilized by Self-Assembled Saponin Nanofibrils and Fibrillar Network.
Nanofibrils from the self-assembly of the naturally occurring saponin glycyrrhizic acid (GA) can be used to produce an oil-in-water emulsion foam with a long-term stability. Through homogenization and aeration followed by rapid cooling, stable emulsion foams can be produced from the mixtures of sunflower oil and saponin nanofibrils. At high temperatures, the GA fibrils form a multilayer assembly at the interface, creating an interfacial fibrillar network to stabilize the oil droplets and air bubbles generated during homogenization. A subsequent rapid cooling can trigger the self-assembly of free GA fibrils in the continuous phase, forming a fibrillar hydrogel and thus trapping the oil droplets and air bubbles. The viscoelastic bulk hydrogel showed a high yield stress and storage modulus, which lead to a complete arrest of the liquid drainage and a strong slowdown of the bubble coarsening in emulsion foams. The jamming of the emulsion droplets in the liquid channels as well as around the bubbles was also found to be able to enhance the foam stability. We show that such stable foam systems can be destroyed rapidly and on demand by heating because of the melting of the bulk hydrogel. The reversible gel-sol phase transition of the GA hydrogel leads to thermoresponsive emulsion foams, for which the foam stability can be switched from stable to unstable states by simply raising the temperature. The emulsion foams can be further developed to be photoresponsive by incorporating internal heat sources such as carbon black particles, which can absorb UV irradiation and convert the absorbed light energy into heat. This new class of smart responsive emulsion foams stabilized by the natural, sustainable saponin nanofibrils has potential applications in the food, pharmaceutical, and personal care industries.


Different subcellular distribution of caspase-3 and caspase-7 following Fas-induced apoptosis in mouse liver.
Caspases plays a key role in the execution phase of apoptosis. "Initiator" caspases, such as caspase-8, activate "effector" caspases, such as caspase-3 and -7, which subsequently cleave cellular substrates thereby precipitating the dramatic morphological changes of apoptosis. Following treatment of mice with an agonistic anti-Fas antibody to induce massive hepatocyte apoptosis, we now demonstrate a distinct subcellular localization of the effector caspases-3 and -7. Active caspase-3 is confined primarily to the cytosol, whereas active caspase-7 is associated almost exclusively with the mitochondrial and microsomal fractions. These data suggest that caspases-3 and -7 exert their primary functions in different cellular compartments and offer a possible explanation of the presence of caspase homologs with overlapping substrate specificities. Translocation and activation of caspase-7 to the endoplasmic reticulum correlates with the proteolytic cleavage of the endoplasmic reticular-specific substrate, sterol regulatory element-binding protein 1. Liver damage, induction of apoptosis, activation and translocation of caspase-7, and proteolysis of sterol regulatory element-binding protein 1 are all blocked by the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD. fmk). Our data demonstrate for the first time the differential subcellular compartmentalization of specific effector caspases following the induction of apoptosis in vivo.


Comparison between Hilbert-Huang transform and scalogram methods on non-stationary biomedical signals: application to laser Doppler flowmetry recordings.
A significant transient increase in laser Doppler flowmetry (LDF) signals is observed in response to a local and progressive cutaneous pressure application on healthy subjects. This reflex may be impaired in diabetic patients. The work presents a comparison between two signal processing methods that provide a clarification of this phenomenon. Analyses by the scalogram and the Hilbert-Huang transform (HHT) of LDF signals recorded at rest and during a local and progressive cutaneous pressure application are performed on healthy and type 1 diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic and endothelial related metabolic activities, are studied at different time intervals in order to take into account the dynamics of the phenomenon. The results show that both the scalogram and the HHT methods lead to the same conclusions concerning the comparisons of the myogenic, neurogenic and endothelial related metabolic activities-during the progressive pressure and at rest-in healthy and diabetic subjects. However, the HHT shows more details that may be obscured by the scalogram. Indeed, the non-locally adaptative limitations of the scalogram can remove some definition from the data. These results may improve knowledge on the above-mentioned reflex as well as on non-stationary biomedical signal processing methods.


Microtubule-assisted altered trafficking of astrocytic gap junction protein connexin 43 is associated with depletion of connexin 47 during mouse hepatitis virus infection.
Gap junctions (GJs) are important for maintenance of CNS homeostasis. GJ proteins, connexin 43 (Cx43) and connexin 47 (Cx47), play a crucial role in production and maintenance of CNS myelin. Cx43 is mainly expressed by astrocytes in the CNS and forms gap junction intercellular communications between astrocytes-astrocytes (Cx43-Cx43) and between astrocytes-oligodendrocytes (Cx43-Cx47). Mutations of these connexin (Cx) proteins cause dysmyelinating diseases in humans. Previously, it has been shown that Cx43 localization and expression is altered due to mouse hepatitis virus (MHV)-A59 infection both in vivo and in vitro; however, its mechanism and association with loss of myelin protein was not elaborated. Thus, we explored potential mechanisms by which MHV-A59 infection alters Cx43 localization and examined the effects of viral infection on Cx47 expression and its association with loss of the myelin marker proteolipid protein. Immunofluorescence and total internal reflection fluorescence microscopy confirmed that MHV-A59 used microtubules (MTs) as a conduit to reach the cell surface and restricted MT-mediated Cx43 delivery to the cell membrane. Co-immunoprecipitation experiments demonstrated that Cx43-β-tubulin molecular interaction was depleted due to protein-protein interaction between viral particles and MTs. During acute MHV-A59 infection, oligodendrocytic Cx47, which is mainly stabilized by Cx43 in vivo, was down-regulated, and its characteristic staining remained disrupted even at chronic phase. The loss of Cx47 was associated with loss of proteolipid protein at the chronic stage of MHV-A59 infection.


(5Z)-carbacyclin displays agonist-antagonist properties on prostacyclin-receptors in platelets and vascular myocytes.
(5E)- and (5Z)-carbacyclin are chemically stable analogues of prostacyclin (PGI2), which mimic PGI2 actions. In particular, they inhibit platelet aggregation and relax vascular smooth muscle, through the activation of adenylate cyclase (AC) being, however, less potent than PGI2. The characteristics of AC activity modulation by the two isomeric carbacyclins in membranes of human platelets and of myocytes cultured from rabbit mesenteric artery have been investigated. In human platelet membranes, both carbacyclins stimulated AC activity with the same efficacy as PGE1 and PGI2; in addition, these two prostaglandins inhibited the aggregation of human and rabbit platelets to the same extent as PGE1. On the contrary, in myocytes (5Z)-carbacyclin fails to produce the same degree of stimulation of AC elicited by PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of rabbit mesenteric artery attained with the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of AC by PGE1, PGI2 or (5E)-carbacyclin, acting therefore as a partial agonist. In conclusion, (5Z)-carbacyclin is a full agonist at the platelet level both in human and rabbit, thus excluding possible interspecies differences, but it is a partial agonist on myocytes. Therefore, (5Z)-carbacyclin appears to discriminate between PGI2 -receptors in the two target cells.


[Decrease of haptoglobin serum level in patients with chronic viral hepatitis C].
Serum levels of haptoglobin, an acute phase protein, in usually increased in patients with inflammation and decreased in patients with intravascular hemolysis. Changes in haptoglobin serum levels were also observed in patients with liver disease. The aim of this study was to evaluate the serum level of haptoglobin in patients with chronic viral hepatitis C. Haptoglobin serum levels were measured by rate nephelometry in 34 patients with histologically proven chronic viral hepatitis C and in 30 controls. Haptoglobin serum levels were lower in patients than in controls (0.56 +/- 0.36 versus 0.90 +/- 0.35 g/L, P < 0.001). In patients with chronic hepatitis but without cirrhosis, haptoglobin serum levels were decreased as well. Haptoglobin serum levels were positively correlated to prothrombin index (P < 0.001) and negatively correlated to the histology activity index of Knodell (P < 0.001), and especially to scores of fibrosis (P < 0.001) and periportal necrosis (P < 0.05). Red cell count, indirect bilirubin level, and reticulocyte count, as markers of hemolysis, were similar in patients and controls. We conclude that determination of haptoglobin serum levels may be useful in the evaluation and the follow-up of patients with chronic viral hepatitis C.


3D-QSAR CoMFA, CoMSIA studies on substituted ureas as Raf-1 kinase inhibitors and its confirmation with structure-based studies.
Three-dimensional quantitative structure activity relationship (3D-QSAR) analyses were carried out on 91 substituted ureas in order to understand their Raf-1 kinase inhibitory activities. The studies include Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Models with good predictive abilities were generated with the cross validated r2 (r2cv) values for CoMFA and CoMSIA being 0.53 and 0.44, respectively. The conventional r2 values are 0.93 and 0.87 for CoMFA and CoMSIA, respectively. In addition, a homology model of Raf-1 was also constructed using the crystal structure of the kinase domain of B-Raf isoform with one of the most active Raf-1 inhibitors (48) inside the active site. The ATP binding pocket of Raf-1 is virtually similar to that of B-Raf. Selected ligands were docked in the active site of Raf-1. Molecule 48 adopts an orientation similar to that inside the B-Raf active site. The 4-pyridyl group bearing amide substituent is located in the adenosine binding pocket, and anchored to the protein through a pair of hydrogen bonds with Cys424 involving ring N-atom and amide NH group. The results of best 3D-QSAR model were compared with structure-based studies using the Raf-1 homology model. The results of 3D-QSAR and docking studies validate each other and provided insight into the structural requirements for activity of this class of molecules as Raf-1 inhibitors. Based on these results, novel molecules with improved activity can be designed.


From mechanism to ecosystem: building bridges between ecoimmunology, psychoneuroimmunology and disease ecology.
Historically, the fields of ecoimmunology, psychoneuroimmunology and disease ecology have taken complementary yet disparate theoretical and experimental approaches, despite sharing critical common themes. Researchers in these areas have largely worked independently of one another to understand mechanistic immunological responses, organismal level immune performance, behavioral changes, and host and parasite/disease population dynamics, with few bridges across disciplines. Although efforts to strengthen and expand these bridges have been called for (and occasionally heeded) over the last decade, more integrative studies are only now beginning to emerge, with critical gaps remaining. Here, we briefly discuss the origins of these key fields, and their current state of integration, while highlighting several critical directions that we suggest will strengthen their connections into the future. Specifically, we highlight three key research areas that provide collaborative opportunities for integrative investigation across multiple levels of biological organization, from mechanisms to ecosystems: (1) parental effects of immunity, (2) microbiome and immune function and (3) sickness behaviors. By building new bridges among these fields, and strengthening existing ones, a truly integrative approach to understanding the role of host immunity on individual and community fitness is within our grasp.


Embodied rules in tool use: a tool-switching study.
In tool use, a transformation rule defines the relation between an operating movement and its distal effect. This rule is determined by the tool structure and requires no explicit definition. The present study investigates how humans represent and apply compatible and incompatible transformation rules in tool use. In Experiment 1, participants had to switch between tools for which the respective transformation rules were either the same or different. This way, rule repetitions could be dissociated from tool repetitions. In Experiment 2, the application of transformation rules in tool use was compared with the application of explicitly defined rules. In Experiment 3, actions of tool use were cued either by tool pictures or by written tool names. The results suggest that a transformation rule in tool use has a cognitive representation that is independent of the concrete tool incorporating it. Furthermore, its application differs from the application of an explicitly defined rule in terms of reduced top-down processing.


[Esophageal varices: physiopathology and treatment. The role of the lower esophageal sphincter].
Development of esophageal varices depends on local esophageal factors and portal gradient, vascular resistance in the azygos vein or presence of other portosystemic collaterals. Esophageal varices are found in the lamina propria of lower esophageal sphincter (LES), the pressure of which exceeds the normal portal pressure. Factors reducing LES pressure promote development of varices and enlarge these. Contraction of LES leads to reduction of the variceal and azygos flows, decrease in the pressure gradient across the varix wall and diminishes the varices. Pharmacological contraction of LES arrests the endoscopically proved bleeding from esophageal varices. Manipulation of LES pressure appears to be a genuine alternative to the current methods of treatment of the bleeding esophageal varices.


Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study.
This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G × E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.


Toll-like receptor 2 regulates CXC chemokine production and neutrophil recruitment to the cornea in Onchocerca volvulus/Wolbachia-induced keratitis.
The filarial nematode Onchocerca volvulus is the causative organism of river blindness. Our previous studies demonstrated an essential role for endosymbiotic Wolbachia bacteria in corneal disease, which is characterized by neutrophil infiltration into the corneal stroma and the development of corneal haze. To determine the role of Toll-like receptors (TLRs) in neutrophil recruitment and activation, we injected a soluble extract of O. volvulus containing Wolbachia bacteria into the corneal stromata of C57BL/6, TLR2-/-, TLR4-/-, TLR2/4-/-, and TLR9-/- mice. We found an essential role for TLR2, but not TLR4 or TLR9, in neutrophil recruitment to the cornea and development of corneal haze. Furthermore, chimeric mouse bone marrow studies showed that resident bone marrow-derived cells in the cornea can initiate this response. TLR2 expression was also essential for CXC chemokine production by resident cells in the cornea, including corneal fibroblasts, and for neutrophil activation. Taken together, these findings indicate that Wolbachia activates TLR2 on resident bone marrow-derived cells in the corneal stroma to produce CXC chemokines, leading to neutrophil recruitment to the corneal stroma, and that TLR2 mediates O. volvulus/Wolbachia-induced neutrophil activation and development of corneal haze.


Gravitropism in Phycomyces: threshold determination on a clinostat centrifuge.
The absolute sensitivity of sporangiophores of Phycomyces blakesleeanus to centrifugal acceleration was determined on a clinostat centrifuge. The centrifuge provides centrifugal accelerations ranging from 10(-4) to 6 x g. The rotor of the centrifuge, which accommodates 96 culture vials with single sporangiophores, is clinostatted, that is, turning "head over", at slow speed (1 rev min(-1)) while it is running. The negative gravitropism of sporangiophores is characterized by two components: a polar angle, which is measured in the plane of bending, and an aiming-error angle, which indicates the deviation of the plane of bending from the vector of the centrifugal acceleration. Dose-response curves were generated for both angles with centrifugations lasting 3, 5, and 8 h. The threshold for the polar angle depends on the presence of statoliths, so-called octahedral protein crystals in the vacuoles. The albino strain C171 carAcarR (with crystals) has a threshold near 10(-2) x g while the albino strain C2 carAgeo-3 (without crystals) has a threshold of about 2 x 10(-1) x g. The threshold for the aiming error angle is ill defined and is between 10(-2) and 10(-1) x g. The threshold for the polar angle of the wild type NRRL 1555 (with crystals) is near 8 x 10(-2) x g.


Facilitators and Barriers in the Implementation of a Digital Surveillance and Outbreak Response System in Ghana Before and During the COVID-19 Pandemic: Qualitative Analysis of Stakeholder Interviews.
In the past 2 decades, many countries have recognized the use of electronic systems for disease surveillance and outbreak response as an important strategy for disease control and prevention. In low- and middle-income countries, the adoption of these electronic systems remains a priority and has attracted the support of global health players. However, the successful implementation and institutionalization of electronic systems in low- and middle-income countries have been challenged by the local capacity to absorb technologies, decisiveness and strength of leadership, implementation costs, workforce attitudes toward innovation, and organizational factors. In November 2019, Ghana piloted the Surveillance Outbreak Response Management and Analysis System (SORMAS) for routine surveillance and subsequently used it for the national COVID-19 response. This study aims to identify the facilitators of and barriers to the sustainable implementation and operation of SORMAS in Ghana. Between November 2021 and March 2022, we conducted a qualitative study among 22 resource persons representing different stakeholders involved in the implementation of SORMAS in Ghana. We interviewed study participants via telephone using in-depth interview guides developed consistent with the model of diffusion of innovations in health service organizations. We transcribed the interviews verbatim and performed independent validation of transcripts and pseudonymization. We performed deductive coding using 7 a priori categories: innovation, adopting health system, adoption and assimilation, diffusion and dissemination, outer context, institutionalization, and linkages among the aspects of implementation. We used MAXQDA Analytics Pro for transcription, coding, and analysis. The facilitators of SORMAS implementation included its coherent design consistent with the Integrated Disease Surveillance and Response system, adaptability to evolving local needs, relative advantages for task performance (eg, real-time reporting, generation of case-base data, improved data quality, mobile offline capability, and integration of laboratory procedures), intrinsic motivation of users, and a smartphone-savvy workforce. Other facilitators were its alignment with health system goals, dedicated national leadership, political endorsement, availability of in-country IT capacities, and financial and technical support from inventors and international development partners. The main barriers were unstable technical interoperability between SORMAS and existing health information systems, reliance on a private IT company for data hosting, unreliable internet connectivity, unstable national power supply, inadequate numbers and poor quality of data collection devices, and substantial dependence on external funding. The facilitators of and barriers to SORMAS implementation are multiple and interdependent. Important success conditions for implementation include enhanced scope and efficiency of task performance, strong technical and political stewardship, and a self-motivated workforce. Inadequate funding, limited IT infrastructure, and lack of software development expertise are mutually reinforcing barriers to implementation and progress to country ownership. Some barriers are external, relate to the overall national infrastructural development, and are not amenable even to unlimited project funding.


Adult golf cart injuries: A rising hazard off the course.
Golf carts are increasingly being used as a means of transportation for travel in neighborhoods, city areas, and unpaved surfaces. The catchment area of our regional trauma center has seen an increase in golf cart use for transportation. In fact, Georgia has recently changed legislation to support the growing need for more defined laws around golf cart use. This study aims to further evaluate injury and outcome patterns in the adult population of northeast Georgia. We performed a retrospective review of adult golf cart injured patients from 2018 to 2022. We evaluated key demographics, such as age and gender, along with the length of stay, Glasgow Coma Scale (GCS), and Injury Severity Score (ISS). Outcomes included the injury type. The results showed that orthopedic injuries were the most common (n = 24). Most patients were in the driver's seat (76%). Ejection from the golf cart was common (82%). Geriatric patients, 65 and older, had an increased length of stay compared to patients under the age of 65 (10 vs 3.9 days). Based on these results, future work includes injury prevention, increased awareness of injury patterns in prehospital and hospital settings, and communities updating their ordinances.


Intracholecystic papillary neoplasm of the gallbladder protruding into the common bile duct: A case report.
The current study indicates the case of intracholecystic papillary neoplasm (ICPN) protruding into the common bile duct (CBD) without superficial spread. A 58-year-old woman presented to hospital with a fever that lasted for three days. Laboratory tests revealed elevated hepatobiliary enzyme levels. CT, MRI and endoscopic ultrasonography revealed a polypoid, papillary tumor inside the gallbladder cavity, which also extended to the CBD. On peroral cholangioscopy, a papillary tumor with mucin production was found at the middle bile duct. Biliary biopsy and bile cytology indicated adenocarcinoma. Based on a diagnosis of ICPN extending to the CBD, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection. However, pathological examination revealed that the ICPN was confined to the gallbladder and cystic duct, whereas the CBD was tumor-free. The present case indicates that when ICPN increases in size, it may protrude into the CBD due to an increased intracholecystic pressure, which increases the risk of overestimation of tumor extension and may result in unnecessary additional bile duct resection.


Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery.
The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log Dlipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log DLPh/RM of exenatide-DOC was 1.2 and -0.9 in simulated intestinal fluid and Hanks' balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.


Flooding impacts on responses of a riparian consumer to cross-ecosystem subsidies.
Landscape-driven processes impact the magnitude and direction of cross-ecosystem resource subsidies, but they may also control consumers' numerical and functional responses by altering habitat availability. We investigated effects of the interaction between habitat availability and subsidy level on populations of a riparian fishing spider, Dolomedes aquaticus, using a flood disturbance gradient in the Waimakariri River catchment, New Zealand. D. aquaticus predominantly eat aquatic prey as they hunt from the water surface. However, D. aquaticus biomass peaked at rivers with intermediate flood disturbance, rather than at less flood-prone rivers where the biomass of aquatic insect prey was markedly higher. Flooding positively influenced spider habitat quality, and an experimental manipulation at stable rivers indicated that unembedded cobbles, preferred D. aquaticus habitat, were a limiting factor, preventing response to the increased prey resource at stable sites. Potential terrestrial prey abundance was low, did not vary across the disturbance gradient, and is likely to have been a much smaller component of the fishing spiders' diet than aquatic insect prey. Thus landscape-driven factors not only controlled the magnitude of resource subsidies, but also influenced the ability of consumers to respond to them by altering the physical nature of the ecosystem boundary.


Take note(s): differential EHR satisfaction with two implementations under one roof.
The aim of this study was to rigorously evaluate perceived differences in satisfaction with an electronic health record (EHR) between residents of two medical specialties who share the same health record, practice location, administration, and information technology support. A cross-sectional survey was used comparing user satisfaction between pediatrics residents and internal medicine residents in an academic practice. The survey was designed to measure baseline demographic characteristics, attitudes toward computers, general satisfaction with an EHR, and perceived practicality of use, variation from familiar practice, organizational support, and impact on delivery of care. Medicine subjects were similar to pediatrics subjects in baseline demographic characteristics. Satisfaction with the EHR implementation was very high for both sets of subjects, but internal medicine residents were significantly less likely to be satisfied with the EHR implementation (relative risk [RR]=0.84, 95% confidence interval [CI]=0.73-0.98) and considerably less likely to believe that their colleagues were satisfied with it (RR=0.56, 95% CI=0.41-0.77). The only surveyed characteristic independently predicting satisfaction was medical specialty (p=0.04). Medicine subjects were less likely to believe template-based documentation improved their efficiency (RR=0.64, 95% CI=0.46-0.88). They were significantly more likely to believe the system had been designed to improve billing (RR=1.50, 95% CI=1.05-2.04) and not to improve patient care (RR=0.61, 95% CI=0.44-0.85). The authors found a difference in satisfaction between internal medicine and pediatrics users of an EHR. Although many potential factors that influence satisfaction were similar between subjects in the two specialties, differences in previous experience may have influenced the results. Medicine residents had more previous experience with a different EHR implementation, which they may have perceived as superior to the one involved in this study. Pediatric residents had more previous experience with structured data entry prior to EHR implementation and more preventive care patient encounters for which structured data entry may be well suited. Since successful implementations generally require satisfied users, understanding what factors affect satisfaction can improve chances of a system's success.


Urinary MicroRNAs as Biomarkers of Urological Cancers: A Systematic Review.
MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.


Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells.
Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-β mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-β. LPS-stimulated dendritic cells release IFN-β which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-β responses which may consequently increase the pathogen load after transmission via tick saliva.


A novel chiral bisphosphine-thiourea ligand for asymmetric hydrogenation of β,β-disubstituted nitroalkenes.
A novel chiral bisphosphine-thiourea ligand was developed and applied in the highly enantioselective hydrogenation of β,β-disubstituted nitroalkenes (up to 99% yield and 99% ee). With low catalytic loading (0.25 mol %), 98% ee and 98% conversion were obtained. The thiourea group takes on an important role in this catalytic system.


Learning a Taxonomy of Predefined and Discovered Activity Patterns.
Many intelligent systems that focus on the needs of a human require information about the activities that are being performed by the human. At the core of this capability is activity recognition. Activity recognition techniques have become robust but rarely scale to handle more than a few activities. They also rarely learn from more than one smart home data set because of inherent differences between labeling techniques. In this paper we investigate a data-driven approach to creating an activity taxonomy from sensor data found in disparate smart home datasets. We investigate how the resulting taxonomy can help analyze the relationship between classes of activities. We also analyze how the taxonomy can be used to scale activity recognition to a large number of activity classes and training datasets. We describe our approach and evaluate it on 34 smart home datasets. The results of the evaluation indicate that the hierarchical modeling can reduce training time while maintaining accuracy of the learned model.


CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients.
Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least six weeks. Multifactorial origin is suggested such as oxidative stress. This latter may play a double role as a trigger and remnant agent. The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: desloratadine 5 mg/d on these different parameters. This study enrolled 30 CSU patients and same number of controls. We assessed the urticaria activity score (UAS), total antioxidant status (TAS), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), albumin, alpha1, alpha2, beta1 beta2, gamma globulins, c-reactive protein (CRP) and hematologic numeration. At baseline alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus controls (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were significantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CRP, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p < 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 d-antihistaminic treatment. Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients' remission was synergistic to CRP attenuation emphasizing CRP relevance for CSU clinical assessment.


Renal angiomyolipomas.
Renal angiomyolipomas are generally benign tumors which are composed of smooth muscle, fat, and blood vessels. Classically these have been diagnosed with the use of arteriograms; however, since ultrasound and CAT scans have come into use these now are the common modalities for diagnosis. All angiomyolipomas generally can be followed conservatively, whereas larger ones have a tendency to bleed and require intervention. This paper reviews the diagnosis, treatment, and prognosis of patients with angiomyolipomas.


Conversion from parenteral to oral methadone.
The described ratio for methadone conversion from oral route (PO) to parenteral route (PAR) is 2:1 and from PAR to PO is 1:2. Frequently, good control of pain with methadone is PR to PO. We use methadone as a function of opioid rotation and not in the context of mortality outcome and we have noted that the traditional ratio produces toxicity problems. We present our experience with patients who we converted from PAR to PO methadone and we recommend a conversion ratio of 0.7 (PO:PAR = 1:0.7), which approximates the bioavailability of the drug administered orally.


Coral microbiome database: Integration of sequences reveals high diversity and relatedness of coral-associated microbes.
Coral-associated microorganisms are thought to play a fundamental role in the health and ecology of corals, but understanding of specific coral-microbial interactions are lacking. In order to create a framework to examine coral-microbial specificity, we integrated and phylogenetically compared 21,100 SSU rRNA gene Sanger-produced sequences from bacteria and archaea associated with corals from previous studies, and accompanying host, location and publication metadata, to produce the Coral Microbiome Database. From this database, we identified 39 described and candidate phyla of Bacteria and two Archaea phyla associated with corals, demonstrating that corals are one of the most phylogenetically diverse animal microbiomes. Secondly, this new phylogenetic resource shows that certain microorganisms are indeed specific to corals, including evolutionary distinct hosts. Specifically, we identified 2-37 putative monophyletic, coral-specific sequence clusters within bacterial genera associated with the greatest number of coral species (Vibrio, Endozoicomonas and Ruegeria) as well as functionally relevant microbial taxa ("Candidatus Amoebophilus", "Candidatus Nitrosopumilus" and under recognized cyanobacteria). This phylogenetic resource provides a framework for more targeted studies of corals and their specific microbial associates, which is timely given the escalated need to understand the role of the coral microbiome and its adaptability to changing ocean and reef conditions.


Spirituality of African-American women: correlations to health-promoting behaviors.
The purpose of this study was to investigate how spirituality relates to health-promoting behaviors in African-American women. Using Burkhart's theoretical framework for spirituality, a descriptive cross-sectional correlational design was used. A group of 260 (N=260) women completed Rosenbergh's Self-Esteem Scale, the Health Promoting Lifestyle Profile II, the Spiritual Perspective Scale, the Brief Block 2000 Food Frequency Questionnaire (FFQ). These women also provided the researchers with their socio-demographic data. Canonical correlation analysis identified a significant pair of canonical variables which indicated that those individuals with good nutrition (.95), physical activity (.79), and healthy eating (.42) were positively associated with stress management (.88), health responsibility (.67), spiritual growth (.66), interpersonal relations (.50), education (.49), and self-esteem (.33). This set of variables explained 56% of the variability (p < .001). Practitioners should incorporate the message of spirituality by focusing on strategies to improve health responsibility, interpersonal relations, and self-esteem, along with health-promoting behaviors.


A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safety and biopsy study.
In a 1-year, placebo-controlled, double-blind, randomized study the long-term effect of Fluticasone Propionate Aqueous Nasal Spray (FPANS) in 42 patients with a perennial allergic rhinitis was studied with regard to safety and efficacy. Twenty-nine patients completed the entire treatment period. After 1 year of treatment no deleterious changes consequent on therapy were observed in nasal mucosal biopsies. The appearance of the epithelial layer, the degree of cellular infiltration, the extent to which the sinusoids were dilated and the degree of tissue oedema improved or remained unchanged in 93% of the patients of the FPANS group, versus 75% of the placebo group, and worsened in 7% of the FPANS group versus 25% of the placebo group. Assessment of the changes in haematological, biochemical, urinary, plasma cortisol levels, and in the findings during nasal examination revealed no significant differences between the two treatment groups. After 1 year of treatment symptom scores for sneezing, nasal itching, and total symptom score were significantly better in the FPANS treated group (P < 0.05, P < 0.05, P < 0.01). An initial reduction in total symptom score was found after 4 weeks FPANS treatment with a further reduction after 8 months of FPANS treatment. These findings suggest that the maximum efficacy of topical intranasal steroids is reached after long-term treatment, and thus advocates longer usage before treatment is stopped because of presumed inefficacy.


A fatal case of hemophagocytic lymphohistiocytosis due to neonatal lupus erythematosus.
Neonatal lupus erythematosus (NLE) is an autoimmune disease caused by the passive transfer of autoantibodies from mother to child during pregnancy. A rare complication of NLE is hemophagocytic lymphohistiocytosis (HLH), a potentially life-threatening hyperinflammatory state more commonly associated with other rheumatologic disorders. Herein, we describe a fatal case of NLE-associated HLH.


Improving laboratory usage: a review.
Influencing the ordering of laboratory investigations, and in particular reducing unnecessary ones, is a vital concern to many hospitals. An account of the reasons why control is necessary is presented. The different methods evaluated are reviewed, including rationing, form design, resource management (budget control), education, protocols and decision support systems, incentives, feedback and case note appraisal. Methods of controlling the requesting of investigations are likely to be ineffective unless they take place in the correct environment. Elements of this include correct attitude and commitment by senior staff, a long term strategy, and different approaches for different groups of doctors.


[Evaluation of tumor heterogeneity for esophageal squamous cell cancer by dynamic FDG-PET].
The aim of this study is to assess the tumor heterogeneity of esophageal squamous cell cancer by dynamic FDG-PET (dPET). Thirty patients were enrolled in this study. Images were obtained after intravenous injection of 370 MBq of 18F-FDG for 1 h. The time-density curve of the standardized uptake value( SUV) was evaluated quantitatively by fractal analysis. Tumor fractal dimension (FD) maps were acquired, and the FD of the tumor was measured. There was a significant correlation between FD and the clinical response to adjuvant therapy. The FD reduction rates of adjuvant therapy were 23.23% in the responder group and 5.83% in the nonresponder group. FD may be a valid imaging biomarker for assessing the response to neoadjuvant therapy.


Ecological validity of the Multiple Errands Test using predictive models of dysexecutive problems in everyday life.
The"dysexecutive syndrome" is composed of a range of cognitive, emotional, and behavioral deficits that are difficult to evaluate using traditional neuropsychological tests. The Multiple Errands Test (MET) was originally developed to systematize the assessment of the more elusive manifestations of the dysexecutive syndrome. The aims of this study were to examining the reliability of the MET and to investigate the predictive ability of its indices to explain a range of "dysexecutive"-related symptoms in everyday life. Thirty patients with acquired brain injury participated in this study. The MET showed an adequate inter-rater reliability and ecological validity. The main performance indices from the MET were able to significantly predict severity of everyday life executive problems, with different indices predicting particular manifestations of different components of executive functions.


[Smoking cessation for COPD].
Smoking cessation is the most effective intervention to prevent the annual decline in lung function in patients with chronic obstructive pulmonary disease. All primary healthcare providers should routinely ask all patients whether tobacco use is active or not, and advise tobacco users to stop smoking. In Japan a treatment of nicotine addiction with varenicline or nicotine patch has been started under health insurance coverage since 2006. About half of the patients taking varenicline could stop smoking. Education on the health risks of smoking in schools for younger ages is essential for prevention of COPD.


[Clinical nutrition therapy in patients with short bowel syndrome in line with principles of personalized medicine].
Home parenteral nutrition administered in selected care centres has been financed in Hungary since January, 2013. The authors discuss diagnostic issues, treatment and nutrition therapy of short bowel syndrome patients in line with the principles of personalised medicine. The most severe form of short bowel syndrome occurs in patients having jejunostomy, whose treatment is discussed separately. The authors give a detailed overview of home parenteral feeding, its possible complications, outcomes and adaptation of the remaining bowel. They describe how their own care centre operates where they administer home parenteral nutrition to 12 patients with short bowel syndrome (5 females and 7 males aged 51.25±14.4 years). The body mass index was 19.07±5.08 kg/m2 and 20.87±3.3 kg/m2, skeletal muscle mass was 25.7±6.3 kg and 26.45±5.38 kg, and body fat mass was 14.25±8.55 kg and 11.77±2.71 kg at the start of home parenteral nutrition and presently, respectively. The underlying conditions of short bowel syndrome were tumours in 4 patients, bowel ischaemia in four patients, surgical complications in three patients, Crohn's disease in one patient, and Crohn's disease plus tumour in one patient.


Human papillomaviruses-related cancers. Presence and prevention strategies in the Middle east and north African regions.
Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region.


Changes in digestive cancer diagnosis during the SARS-CoV-2 pandemic in Italy: A nationwide survey.
The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed. To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy. A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017-2020. Non-parametric ANOVA for repeated measurements was applied to compare distributions by years and macro-areas. Compared to 2019, in 2020 gastric cancer diagnoses decreased by 15.9%, CRC by 11.9% and pancreatic by 9.9%. CRC distributions showed significant differences between all years, stomach cancer between 2018 and 2020 and 2019-2020, and pancreatic cancer only between 2017 and 2019. The 2019-2020 comparison showed fewer CRC diagnoses in the North (-13.7%), Center (-16.5%) and South (-4.1%), fewer stomach cancers in the North (-19.0%) and South (-9.4%), and fewer pancreatic cancers in the North (-14.1%) and Center (-4.7%), with an increase in the South (+12.3%). Distributions of CRC and gastric cancer were significantly different between all years in the North. This survey highlights the concerning effects of the COVID-19 pandemic on the diagnostic yield of gastroenterology services for stomach, colorectal and pancreatic cancers in Italy.


Contraception and sexual health in obese women.
As the proportion of women with obesity increases worldwide, understanding the influence of body weight on sexual behavior, fertility, and contraceptive effectiveness is critical for health-care professionals and patients. Although many have theorized that obese women are different from normal-weight women regarding sexual health and behavior, current evidence for the most part disproves this. The exception is in adolescents where body image may play a role in riskier behavior, placing them at a greater risk of an unintended pregnancy. Given that most modern contraceptives were not originally evaluated in obese women, understanding how weight affects contraceptive pharmacokinetics and efficacy should be a focus of ongoing research. Evidence is reassuring that most modern contraceptive methods are safe and effective in obese women. This paper reviews what is known about sexual and contraceptive behavior, as well as the effectiveness and pharmacokinetics of modern contraceptives, for overweight and obese women.


Evaluating physical therapy students' knowledge of and adherence to the ambassador low back pain guideline.
To examine a process for evaluating physiotherapy (PT) students' knowledge of and adherence to the Ambassador Low Back Pain (LBP) guideline using vignettes. The study used a cross-sectional survey design. Participants were PT students who had received information related to the guideline as part of their curriculum. Primary measures were responses to questions about the management of four clinical vignettes. Adherence to guideline recommendations was measured by comparing participant scores to a "guideline-based" set of responses from a physiotherapist involved in developing the Ambassador guideline, which was considered a criterion standard. A total of 74 respondents provided complete data, for a response rate of 89%; 65 (88%) reported no knowledge of the guideline. Overall consistency with the criterion standard was high (>70%). Respondents demonstrated high adherence when identifying red flags and deciding whether to refer to another provider. Despite known exposure, knowledge of the guideline was low in this sample of Canadian PT students. Nevertheless, in several key areas, unconscious adherence was high relative to the guideline-based criterion standard. With minor modifications, the vignettes are suitable for evaluating the Ambassador LBP guidelines in a larger study.


Progressive histoplasmosis with hemophagocytic lymphohistiocytosis and epithelioid cell granulomatosis: A case report and review of the literature.
Histoplasmosis in central Europe is a rare fungal disease with diverse clinical presentations. Apart from acute pulmonary histoplasmosis and involvement of the central nervous system, the most serious clinical presentation is progressive disseminated histoplasmosis which is generally associated with severe immunodeficiency and, in particular, advanced human immunodeficiency virus infection. Here, we report on an immunocompetent female residing in a non-endemic area, presenting with progressive disseminated histoplasmosis after a remote travel history to Thailand and Costa Rica. Diagnosis was delayed by several months due to misinterpretation of epithelioid cell granulomatosis of the intestine as Crohn's disease and of similar lung lesions as acute sarcoidosis. Prompted by clinical deterioration with signs and symptoms consistent with hemophagocytic lymphohistiocytosis, a bone marrow aspiration was performed that documented hemophagocytosis and intracellular organisms interpreted as Leishmania sp., but later identified by molecular methods as Histoplasma capsulatum. Treatment with liposomal amphotericin B followed by posaconazole led to prompt clinical improvement and ultimately cure.


Epidemiological characteristics of pertussis in Estonia, Lithuania, Romania, the Czech Republic, Poland and Turkey-1945 to 2005.
Pertussis epidemiology was examined in selected Central and Eastern European countries andTurkey (CEEs) from 1945 to 2005. Epidemiology and immunisation coverage data were collected fromNational Health Departments and Epidemiology Institutes. Pertussis diagnosis was made by the World Health Organization (WHO) clinical criteria, laboratory confirmation and/or epidemiological link, except for Romania (WHO clinical case definition used). In the pre-vaccine era, pertussis incidence (except Turkey) exceeded 200/100,000 (range180-651/100,000), with 60-70% of cases occurring in pre-school children. Until 2007, a second-year booster was givenin Estonia, Lithuania and Turkey, and an additional pre-school booster elsewhere. During 1995-2005, immunisation coverage by the age of 2 years exceeded 80% (range 80-98%) and, excluding Estonia, pertussis incidence was <3/100,000. Age-specific incidence rates rose in 5-14 year olds in Poland, Estonia and the Czech Republic. Incidence rates in children <1 year of age remained unchanged. There were two age distribution patterns. In the Czech Republic and Estonia, 16% of cases occurred in pre-school children and 17% and 22% in children >15 years of age, respectively; in Romania, Turkey and Lithuania, 51%, 71% and 73%, respectively, occurred in pre-school children and <7% in children aged >15 years.Pertussis infection persists, despite high immunisation coverage. Compared with the pre-vaccine era, the age distribution changed differentially in CEEs, with an apparent shift towards older children.


Isolated hypogonadotropic hypogonadism in a man with a history of head trauma during childhood.
To report a case of isolated hypogonadotropic hypogonadism as a delayed consequence of major head injury. We present the relevant history, findings on physical examination, and results of laboratory evaluation, and supportive data from appropriate reports in the literature are reviewed. A 37-year-old man with progressive loss of libido, impotence, and gradual loss of facial and axillary hair had sustained severe trauma to the head (sufficient to cause blindness in one eye) in a fall from a tree at 7 years of age. Physical examination and laboratory investigations substantiated the presence of isolated hypogonadotropic hypogonadism. Other causes of hypogonadotropic hypogonadism, including Kallmann's syndrome, were excluded. Severe head injury should be considered in the differential diagnosis of isolated hypogonadotropic hypogonadism. Long-term follow-up and endocrine assessment may be important in patients who have sustained severe head injury.


Korean physician prescription patterns for home oxygen therapy in chronic obstructive pulmonary disease patients.
Hypoxemia in chronic obstructive pulmonary disease (COPD) leads to reduced ability to exercise, decreased quality of life, and, eventually, increased mortality. Home oxygen therapy in patients with severe COPD reduces distress symptoms and mortality rates. However, there have been few studies on physicians' prescription behavior toward home oxygen therapy. Therefore, we investigated the respiratory specialists' perspective on home oxygen therapy. In this cross-sectional, study, a questionnaire was completed by 30 pulmonary specialists who worked in tertiary hospitals and prescribed home oxygen therapy. The questionnaire consisted of 28 items, including 15 items on oxygen prescription for outpatients, four for inpatients, and nine on service improvement. All physicians were prescribing less than 2 L/min of oxygen for either 24 (n = 10, 33.3%) or 15 hours (n = 9, 30.3%). All (n = 30) used pulse oximetry, 26 (86.7%) analyzed arterial blood gas. Thirteen physicians had imposed restrictions and recommended oxygen use only during exercise or sleep. Sixteen (53.3%) physicians were educating their patients about home oxygen therapy. Furthermore, physicians prescribed home oxygen to patients that did not fit the typical criteria for long-term oxygen therapy, with 30 prescribing it for acute relief and 17 for patients with borderline hypoxemia. This study identified the prescription pattern of home oxygen therapy in Korea. Respiratory physicians prescribe home oxygen therapy to hypoxemic COPD patients for at least 15 hours/day, and at a rate of less than 2 L/min. More research is needed to provide evidence for establishing policies on oxygen therapy in COPD patients.


Inhibition of murine lymphokine-activated killer (LAK) cell activity by adherent cells.
The effects of adherent cell depletion, indomethacin, and prostaglandin E2 (PGE2) on murine LAK cell activity were investigated. Removal of plastic adherent cells from splenocyte suspensions either prior to 5-day culture with 1000 U/ml of recombinant human IL-2 (rIL-2) or prior to assay resulted in an enhanced LAK cell cytotoxicity compared to that of whole spleen cell suspensions. Indomethacin enhanced LAK cell cytotoxicity of whole splenocyte suspensions if present during the culture period, but had no effect on whole splenocyte or adherent cell-depleted cell suspensions if added just prior to assay. PGE2 suppressed LAK cell activity of nonadherent splenocyte but not whole splenocyte suspensions when present during the culture period. In vivo treatment of mice with indomethacin enhanced cytotoxicity directed toward both LAK sensitive, natural killer (NK) resistant (P-815) and LAK, NK sensitive (YAC-1) tumor cell targets. Splenocytes from indomethacin-treated mice cultured with additional indomethacin and rIL-2 exhibited highest LAK cell activity. The results from this study indicate that LAK cells are regulated by adherent cells which suppress LAK cell activity. This suppression can be reversed both in vitro and in vivo by indomethacin. This study has important implications for the possible clinical use of indomethacin in the potentiation of in vivo and in vitro LAK cell activity for immunotherapeutic protocols.


[Study on the method of measurement of respiratory mechanical parameters].
Respiratory mechanical parameters are the key indexes in evaluating the respiratory function of an anaesthetized patient during operation. The measurement of respiratory parameters plays an important role in clinic, and can dynamically monitor the working state of a respirator, direct the use of a respirator and monitor the respiratory function of a patient in intensive care unit(ICU). This paper introduces a new method that will break the traditional limitations, can measure eleven respiratory parameters and demonstrate the results by digital and diagrams.


Pulmonary dirofilariasis in man: a new Italian case. Review of the European literature.
In June 1991 a 62-year-old retired man, from Udine (northern Italy), was suddenly affected by dyspnoea. X-ray and CT control detected a coin lesion in the lung, in May 1992 this lesion was removed surgically. Histological examination revealed the presence of a nematode inside an arteriole which had provoked a small infarct in the pulmonary tissue. The parasite presented marked regressive phenomena that made an accurate morphological analysis impossible. However, in the light of certain details of the cuticle, and by analogy with four similar cases occurring in northern Italy, as well as 10 others (nine subcutaneous and one submucosa) reported in man from the same region (Venetia) over the last 15 years, the aetiologic agent was thought to be Dirofilaria (N.) repens. Over all 10 cases of human pulmonary dirofilariasis were reported in Europe: five in Italy, probably by D (N.) repens, two in Germany, in patients coming from Corsica and two in Spain (only by serology), attributed to D. immitis. In addition one case was reported in U.S.A. in a man who previously visited Italy.