The conundrum of claudication.
Stable claudication has traditionally been treated conservatively by many clinicians as operative therapies involve considerable risk for a condition that is often slowly progressive and non-fatal. The relative safety of less invasive endovascular techniques brings potential survival benefits from the increased exercise tolerance that result. We aimed to revisit and clarify the aetiologies of intermittent claudication in a review of the rarer causes that can mimic atherosclerotic occlusive disease. An extensive search of Medline, Embase and the Cochrane databases was carried out to compile published work addressing the aetiology of claudication and specific non-atherosclerotic causes. The reference lists of these manuscripts were also searched for relevant articles. There are several vasculogenic and neurogenic causes for intermittent claudication, many of which are unrelated to atherosclerosis. Recognition of these rarer syndromes is essential when planning endovascular or operative management strategies. Consideration of non-atherosclerotic differential diagnoses is recommended when assessing the patient with intermittent claudication. This is particularly critical in the young patient whose pattern of symptoms and risk factors may not fit precisely with atherosclerosis.


Self-Organized Freestanding One-Dimensional Au Nanoparticle Arrays.
One-dimensional Au nanoparticle arrays encapsulated within freestanding SiO2 nanowires are fabricated by thermal oxidation of Au-coated Si nanowires with controlled diameter and surface modulation. The nanoparticle diameter is determined by the Si nanowire diameter and Au film thickness, while the interparticle spacing is independently controlled by the Si nanowire modulation. The optical absorption of randomly oriented Au nanoparticle arrays exhibits a strong plasmonic response at 550 nm. Scanning transmission electron microscopy (STEM)-electron energy loss spectrum (EELS) of nanoparticle arrays confirmed the same plasmonic response and demonstrated uniform optical properties of the Au nanoparticles. The plasmonic response in the STEM-EELS maps is primarily confined around the vicinity of the nanoparticles. On the other hand, examination of the same nanowires by energy-filtered transmission electron microscopy also revealed significant enhancement in the plasmonic excitation in the regions in between the nanoparticles. This versatile route to synthesize one-dimensional Au nanoparticle arrays with independently tailorable nanoparticle diameter and interparticle spacing opens up opportunities to exploit enhanced design flexibility and cost-effectiveness for future plasmonic devices.


Cortisol and treatment effect in children with disruptive behavior disorders: a preliminary study.
Basal cortisol and cortisol stress responsivity are valuable biological characteristics of children with disruptive behavior disorder (DBD). In this study, the predictive value of cortisol to outcome of intervention was investigated. Basal cortisol levels and cortisol levels under stress were studied in 22 children with DBD before the start of a psychotherapeutic treatment. The disruptive behavior of the child was assessed before treatment and after cessation (9 months later). Children with DBD with relatively high and low basal cortisol levels differed in the severity of problem behavior at pretreatment, with the low basal cortisol group having more severe problems. During stress, children with DBD showed either increasing or decreasing cortisol values. Although these cortisol responsivity groups were similar in the severity of behavioral problems at pretreatment, the behavioral problems of the group with high cortisol stress responsivity were significantly lower after the intervention than the behavioral problems of the group with low cortisol stress responsivity. In children with DBD, the basal cortisol level was related to the severity of behavioral problems at pretreatment but not to the severity of behavioral problems after treatment. The cortisol response pattern during stress was related to treatment outcome.


The effects of endodontic substances and naturally reducing agents on the bond strength of epoxy resin-based sealer to root dentin.
To evaluate the effects of sodium hypochlorite (NaOCl), chlorhexidine (CHX), and two naturally derived reducing agents on the bond strength of epoxy resin-based sealer to root dentin. A total of 60 single-rooted human teeth were prepared using ProTaper (Dentsply Tulsa Dental Specialties, Johnson City, TN, USA) and an irrigation protocol including 5% NaOCl or 2% CHX gel, and ethylenediaminetetraacetic acid (EDTA), for smear layer removal. The following subgroups (n = 10) were also assessed according to the naturally derived reducing agent used: no agent (control group); grape seed extract (GSE); and green tea. Root canals were filled with gutta-percha and AH Plus (Dentsply DeTrey, Konstanz, Germany). Bond strength was measured using the push-out test, and statistical analyses were performed using ANOVA; failure patterns (modes) were classified as adhesive, cohesive, or mixed. The types of failure modes were evaluated using the Chi-squared test at α =0.05. The irrigation protocols demonstrated similar bond strength values (P > 0.05). However, the Chi-squared test revealed significant differences in failure mode among the groups (P < 0.05). An increase in the incidence of adhesive failures was observed for the NaOCl and EDTA groups. The other groups demonstrated a prevalence of mixed and cohesive failures. The irrigation protocols and use of naturally derived reducing agents had no effect on the bond strength of the resin-based sealer to dentin; however, improvement was evident in the adhesion quality of AH Plus to NaOCl-treated root dentin, due to the prevalence of cohesive failure.


A Prospective Comparison of Transcutaneous and Serum Bilirubin Within Brief Time Intervals.
The American Academy of Pediatrics recommends screening newborns ≥35 weeks' gestation with total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) to detect hyperbilirubinemia. Retrospective studies show TcB measurements strongly correlate with TSB; however, few prospective trials document this relationship. Furthermore, Dräger's newest TcB instrument, JM-105, remains unstudied in the United States. We measure TcB on foreheads and sternums of newborns using JM-105 and Bilichek devices within 30 minutes of TSB measurement. We find best overall TcB/TSB correlation with JM-105 on the sternum (mean TcB-TSB difference: -0.21 ± 1.15 mg/dL). Correlations between paired measurements for TcB on the sternum using JM-105 were 0.93 for all TSB levels (n = 178), 0.82 for TSB > 10 (n = 19), 0.69 for TSB > 12 (n = 11), and 0.52 for TSB > 15 (n = 6). TcB accuracy via JM-105 on the sternum significantly differed among races ( P < .001). For 5% of paired measurements, TcB with JM-105 on the sternum underestimated TSB by ≥2 mg/dL, and for <1% by ≥3 mg/dL.


Detection of genome-edited mutant clones by a simple competition-based PCR method.
Genome editing by the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats / CRISPR-associated protein 9) system is a revolutionary strategy to study gene functions. Since the efficiency of gene disruption in cell culture does not reach 100% typically, cloning of mutant cells is often performed to obtain fully mutated cells. Therefore, a method to discriminate accurately mutated clones easily and quickly is crucial to accelerate the research using CRISPR/Cas9. Here, we show that knockout cells can be discriminated by a competition-based PCR, using a mixture of three primers, among which one primer overlaps with the Cas9 cleavage site. Together, we show how to optimize primer design in order to improve the effectiveness of the discrimination. Finally, we applied this method to show that mutations conferring drug resistance can be detected with high accuracy. The provided method is easy to perform and requires only basic laboratory equipment, making it suitable for almost all laboratories.


Role of PKCα activation of Src, PI-3K/AKT, and ERK in EGF-stimulated proliferation of rat and human conjunctival goblet cells.
To determine the order and components of the signaling pathway utilized by epidermal growth factor (EGF) to stimulate conjunctival goblet cell proliferation. Goblet cells from rat bulbar and forniceal conjunctiva and human bulbar conjunctiva were grown in organ culture. Goblet cells (GCs) were serum starved for 24 hours and preincubated with inhibitors for 30 minutes or small interfering RNA (siRNA) for 48 hours prior to addition of EGF. Proliferation was then measured or Western blot analysis was performed using antibodies against phosphorylated protein kinase B (AKT), extracellular signal-regulated kinase 1/2 (ERK1/2), or the non-receptor tyrosine kinase Src. Rat GCs were also incubated with adenoviruses expressing dominant negative protein kinase Cα (DNPKCα) or constitutively activated protein kinase Cα (myrPKCα), and activation of AKT and ERK1/2 was determined by Western blot analysis. Inhibitors of phosphoinositol-3 kinase (PI-3K)/AKT pathway blocked EGF-stimulated ERK1/2 activation and GC proliferation. Inhibitors of EGF-stimulated ERK1/2 activity did not inhibit AKT activation but blocked proliferation. DNPKCα blocked EGF-stimulated activation of AKT and ERK1/2 while myrPKCα increased activation of these kinases. Inhibitors of PI-3K, ERK1/2, and protein kinase C (PKC) blocked myrPKCα-stimulated GC proliferation. EGF and myrPKCα increased phosphorylation of Src, and inhibition of Src with the chemical inhibitor PP1 or siRNA inhibited EGF-stimulated GC proliferation. We found that EGF activates a major pathway to stimulate goblet cell proliferation. This pathway consists of induction of phospholipase C (PLC)γ to activate PKCα. Active PKCα phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation.


[Determination of tin in food products using pyrocatechol violet].
Some incorrect points are referred to of Part II of Bulgarian State Standard 6853-74 "Canned fruits, vegetables, meat, and meat-and-vegetables. Determining the content of stannum with the use of pyrocatecholviolet" rendering difficult the analytic process and leading to false results. Another method for the evaluation of the stannum content making use of pyrocatecholviolet has been applied instead as suggested by the International Federation of Chemists. It makes feasible the determination of even small amounts of stannum (0-30 mug) which are usually encountered in the food products. A mathematic and statistical processing of the results obtained has been made.


Design of P-Chirogenic Aminophosphine-Phosphinite Ligands at Both Phosphorus Centers: Origin of Enantioselectivities in Pd-Catalyzed Allylic Reactions.
We have recently patented an unprecedented stereospecific N → O phosphinyl migration process which transforms P-chirogenic aminophosphines into phosphinites. A fine design of aminophosphine phosphinite ligands (AMPP*) derived from ephedrine and bearing a P-chirogenic center either at the aminophosphine or phosphinite moiety was performed. The synthesis of AMPP* ligands with a P-chirogenic aminophosphine moiety was based on the well-established stereospecific reaction of oxazaphospholidine borane with organolithium reagents, followed by trapping with a chlorophosphine and borane decomplexation. Concurrently, the preparation of AMPP* ligands with a P-chirogenic phosphinite moiety was performed by N → O phosphinyl migration of aminophosphines borane by heating at 50 °C with DABCO and then reaction with chlorophosphines. AMPP* ligands were studied in palladium-catalyzed asymmetric allylic alkylations, leading to enantioselectivities from 91% (R) to 95% ee (S). X-ray crystallographic data for relevant Pd-AMPP* complexes and computer modeling explained the origin of the enantioselectivities based on MO interactions of most stable conformers with nucleophiles.


Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats.
The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voriconazole), and multiple-dose group (multiple doses of 30 mg/(kg•day) per dose of voriconazole). Each group of rats was given an oral dose of 10 mg/kg vonoprazan 30 min after the administration of voriconazole or vehicle. After the oral administration of vonoprazan, 50 µL of blood was collected into 1.5-mL heparinized tubes via the caudal vein. The concentration of vonoprazan in plasma was quantified by ultra-performance liquid chromatography/tandem mass spectrometry. Both in vitro effects of voriconazole on vonoprazan and the mechanism of the observed inhibition were studied in rat liver microsomes. When orally administered, voriconazole increased the area under the plasma concentration-time curve (AUC), prolonged the elimination half-life (t1/2), and decreased the clearance (CL) of vonoprazan; there was no significant difference between the single-dose and multiple-dose groups. Voriconazole inhibited the metabolism of vonoprazan at an IC50 of 2.93 μM and showed mixed inhibition. The results of the in vivo experiments were consistent with those of the in vitro experiments. Our findings provide the evidence of drug-drug interactions between voriconazole and vonoprazan that could occur with pre-administration of voriconazole. Thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of vonoprazan in clinical settings.


Nucleotide sequence and evolution of the orangutan epsilon globin gene region and surrounding Alu repeats.
We have mapped and sequenced the epsilon globin gene and seven surrounding Alu repeat sequences in the orangutan beta globin gene cluster and have compared these and other orangutan sequences to orthologously related human sequences. Noncoding flanking and intron sequences, synonymous sites of alpha, gamma, and epsilon globin coding regions, and Alu sequences in human and orangutan diverge by 3.2%, 2.7%, and 3.7%, respectively. These values compare to 3.6% from DNA hybridizations and 3.4% from the psi eta globin gene region. If as suggested by fossil evidence and "molecular clock" calculations, human and orangutan lineages diverged about 10-15 MYA, the rate of noncoding DNA evolution in the two species is 1.0-1.5 X 10(-9) substitutions per site per year. We found no evidence for either the addition or deletion of Alu sequences from the beta globin gene cluster nor is there any evidence for recent concerted evolution among the Alu sequences examined. Both phylogenetic and phenetic distance analyses suggest that Alu sequences within the alpha and beta globin gene clusters arose close to the time of simian and prosimian primate divergence (about 50-60 MYA). We conclude that Alu sequences have been evolving at the rate typical of noncoding DNA for the majority of primate history.


[Determination of benzodiazepines by thermospray liquid chromatograph-mass spectrometer. Part 1. Nitrazepam, estazolam, bromazepam, flunitrazepam].
Thermospray liquid chromatography mass spectrometric method is described for the determination of the benzodiazepines (Nitrazepam, Estazolam, Bromazepam, Flunitrazepam). Reversed-phase liquid chromatography was performed using a 15 cm Shim-pack CLC-ODS (Shimadzu) column, with acetonitrile-water (40:60) + 0.1 M ammonium acetate as mobile phase, at a flow rate of 1.0 ml/min. The temperature of the vaporizer, block and TH of the source block were 166, 270 and 275 degrees C, respectively. Positive ion thermospray mass spectra by thermospray ionization (TSP ionization) mode or thermospray on filament ionization (filament-on ionization) mode were obtained. Formation of the MH+ ion was observed as a base peak under TSP ionization and filament-on ionization conditions and fragment ions were very few. On both ionization mode, peaks representing nitrazepam as MH+ at m/z 282 at a retention time (R.T.) of 6.4 min, from estazolam as MH+ at m/z 295 at an R.T. of 6.4 min, from bromazepam as MH+ at m/z 316 at an R.T. of 4.5 min and from flunitrazepam as MH+ at m/z 314 at an R.T. of 8.8 min. The detection limit for all the benzodiazepines under investigation was less than 0.5 ng (S/N = 9.4 +/- 4.6) using selected ion monitoring.


A Case of Disseminated Coccidioidomycosis: When the Treasure Chest Wall Opened.
Coccidioidomycosis is an infection caused by soil-dwelling fungi, Coccidioides, that are endemic to the southwestern United States, northern Mexico, and scattered areas of Latin America. It typically presents with pulmonary manifestations that resemble symptoms of bronchitis, pneumonia, and the flu. Extrapulmonary manifestations that involve the skin, lymph nodes, bones, and joints have also been well described, but disseminated coccidioidomycosis initially presenting as chest wall infection without pulmonary symptoms is not. In this article, we present a case of a 33-year-old man who presented with chest wall swelling and eventually diagnosed with chest wall abscesses due to disseminated coccidioidomycosis. We propose that consideration of disseminated coccidioidomycosis in nonresolving swelling, mass, lesions, or abscess especially in endemic areas for coccidioidomycosis and in travelers to the endemic area may prevent the progression and further complications of coccidioidomycosis.


Maximum entropy production allows a simple representation of heterogeneity in semiarid ecosystems.
Feedbacks between water use, biomass and infiltration capacity in semiarid ecosystems have been shown to lead to the spontaneous formation of vegetation patterns in a simple model. The formation of patterns permits the maintenance of larger overall biomass at low rainfall rates compared with homogeneous vegetation. This results in a bias of models run at larger scales neglecting subgrid-scale variability. In the present study, we investigate the question whether subgrid-scale heterogeneity can be parameterized as the outcome of optimal partitioning between bare soil and vegetated area. We find that a two-box model reproduces the time-averaged biomass of the patterns emerging in a 100 x 100 grid model if the vegetated fraction is optimized for maximum entropy production (MEP). This suggests that the proposed optimality-based representation of subgrid-scale heterogeneity may be generally applicable to different systems and at different scales. The implications for our understanding of self-organized behaviour and its modelling are discussed.


Recurrent bacterial pneumonia in Irish Wolfhounds: Clinical findings and etiological studies.
Increased incidence of bacterial pneumonia (BP) has been reported in Irish Wolfhounds (IWHs), and recurrence of BP is common. The etiology of recurrent pneumonia in IWHs is largely unknown. To describe clinical findings in IWHs with recurrent BP and investigate possible etiologies. Eleven affected IWHs, 25 healthy IWHs, 28 healthy dogs of other Sighthound breeds, and 16 healthy dogs of other breeds. Prospective cross-sectional observational study. All affected IWHs underwent thorough clinical examinations including thoracic radiographs, thoracic computed tomography, electron microscopic evaluation of ciliary structure, and bronchoscopy and bronchoalveolar lavage fluid (BALF) cytology and culture. Serum and BALF immunoglobulin concentrations were measured using an ELISA method, and peripheral blood lymphocyte subpopulations were analyzed using flow cytometry. Esophageal function was assessed by fluoroscopy (n = 2). Median age of onset was 5.0 years (range, 0.4-6.5 years), and when presented for study, dogs had experienced a median of 5 previous episodes of BP (range, 2-6). The following predisposing factors to BP were detected: focal bronchiectasis (10/11), unilateral (2/9) and bilateral (1/9) laryngeal paralysis, and esophageal hypomotility (2/2). Local or systemic immunoglobulin deficiencies or primary ciliary defects were not detected. Recurrent BP affects mostly middle-aged and older IWHs without any evident immune deficit or primary ciliary defects. Focal BE was a frequent finding in affected dogs and likely contributed to the development of recurrent respiratory infections. Laryngeal and esophageal dysfunction identified in a minority of dogs may contribute to recurrent BP.


Real-Time, In Situ Imaging of Macrophages via Phase-Change Peptide Nanoemulsions.
Macrophages are specialized phagocytes that play central roles in immunity and tissue repair. Their diverse functionalities have led to an evolution of new allogenic and autologous macrophage products. However, realizing the full therapeutic potential of these cell-based therapies requires development of imaging technologies that can track immune cell migration within tissues in real-time. Such innovations will not only inform treatment regimens and empower interpretation of therapeutic outcomes but also enable prediction and early intervention during adverse events. Here, phase-changing nanoemulsion contrast agents are reported that permit real-time, continuous, and high-fidelity ultrasound imaging of macrophages in situ. Using a de novo designed peptide emulsifier, liquid perfluorocarbon nanoemulsions are prepared and show that rational control over interfacial peptide assembly affords formulations with tunable acoustic sensitivity, macrophage internalization, and in cellulo stability. Imaging experiments demonstrate that emulsion-loaded macrophages can be readily visualized using standard diagnostic B-mode and Doppler ultrasound modalities. This allows on-demand and long-term tracking of macrophages within porcine coronary arteries, as an exemplary model. The results demonstrate that this platform is poised to open new opportunities for non-invasive, contrast-enhanced imaging of cell-based immunotherapies in tissues, while leveraging the low-cost, portable, and safe nature of diagnostic ultrasound.


MicroRNAs as therapeutic targets and their potential applications in cancer therapy.
The results of cancer-associated miRNA research have yielded surprising insights into the pathogenesis of a range of different cancers. Many of the dysregulated miRNAs are involved in the regulation of genes that are essential for carcinogenesis. This review discusses the latest discovery of miRNAs acting as oncogenes and tumor suppressor genes, as well as the potential applications of miRNA regulations in cancer therapy. Several translational studies have demonstrated the feasibility of targeting oncogenic miRNAs and restoring tumor-suppressive miRNAs for cancer therapy using in vivo model systems. miRNAs are extensive regulators of cancer progression. With increasing understanding of the miRNA target genes and the cellular behaviors influenced by them, modulating the miRNA activities may provide exciting opportunities for cancer therapy. Despite the hurdles incurred in acquiring effective systemic drug delivery systems, in vivo delivery of miRNAs for therapeutic purposes in preclinical animal models is rapidly developing. Accumulating evidences indicate that using miRNA expression alterations to influence molecular pathways has the potential of being translated into clinical applications.


Application of multiple headspace-solid-phase microextraction followed by gas chromatography-mass spectrometry to quantitative analysis of tomato aroma components.
The objective of this paper is to investigate the potential of multiple headspace-solid-phase microextraction (MHS-SPME) for the determination of volatile compounds in complex matrix samples. A method based on MHS-SPME for the determination of around 20 volatile compounds, responsible of tomato flavour and aroma has been developed and validated, using gas chromatography with mass spectrometry (ion trap analyser) for analysis. For this purpose, the experimental beta parameter, resulting from the MHS-SPME theoretical development, has been obtained from real sample analysis (in triplicate) for each identified compound, carrying out up to 5 consecutive extractions. Later, this parameter is used to perform quantitation of real samples after just a single HS-SPME extraction. Precision, expressed as repeatability, has been evaluated by analysing six replicates of a real sample, showing relative standard deviations between 4 and 20%. For accuracy study, quantitative results have been compared with those obtained by means of standard additions on replicate samples, and no statistically significant differences between the two methods were observed. Since MHS-SPME uses the estimated total area corresponding to the complete extraction of compounds (obtained from the beta parameter), quantitation can be carried out by external calibration using standards in solvent and splitless injection, instead of by SPME. Linearity, tested in the range 0.05-15 microg/mL, showed satisfactory values, with coefficients of correlation between 0.995 and 0.999. Limits of detection were in the range of 0.25-5 ng/g. MHS-SPME has been proved to be an adequate technique to avoid matrix effects in complex samples quantitation. Its applicability to the determination of volatile tomato components, together with its limitations, is discussed in this article.


The electrically conductive pili of Geobacter species are a recently evolved feature for extracellular electron transfer.
The electrically conductive pili (e-pili) of Geobactersulfurreducens have environmental and practical significance because they can facilitate electron transfer to insoluble Fe(III) oxides; to other microbial species; and through electrically conductive biofilms. E-pili conductivity has been attributed to the truncated PilA monomer, which permits tight packing of aromatic amino acids to form a conductive path along the length of e-pili. In order to better understand the evolution and distribution of e-pili in the microbial world, type IVa PilA proteins from various Gram-negative and Gram-positive bacteria were examined with a particular emphasis on Fe(III)-respiring bacteria. E-pilin genes are primarily restricted to a tight phylogenetic group in the order Desulfuromonadales. The downstream gene in all but one of the Desulfuromonadales that possess an e-pilin gene is a gene previously annotated as 'pilA-C' that has characteristics suggesting that it may encode an outer-membrane protein. Other genes associated with pilin function are clustered with e-pilin and 'pilA-C' genes in the Desulfuromonadales. In contrast, in the few bacteria outside the Desulfuromonadales that contain e-pilin genes, the other genes required for pilin function may have been acquired through horizontal gene transfer. Of the 95 known Fe(III)-reducing micro-organisms for which genomes are available, 80 % lack e-pilin genes, suggesting that e-pili are just one of several mechanisms involved in extracellular electron transport. These studies provide insight into where and when e-pili are likely to contribute to extracellular electron transport processes that are biogeochemically important and involved in bioenergy conversions.


DNA Damage Responses Are Induced by tRNA Anticodon Nucleases and Hygromycin B.
Previous studies revealed DNA damage to occur during the toxic action of PaT, a fungal anticodon ribonuclease (ACNase) targeting the translation machinery via tRNA cleavage. Here, we demonstrate that other translational stressors induce DNA damage-like responses in yeast as well: not only zymocin, another ACNase from the dairy yeast Kluyveromyces lactis, but also translational antibiotics, most pronouncedly hygromycin B (HygB). Specifically, DNA repair mechanisms BER (base excision repair), HR (homologous recombination) and PRR (post replication repair) provided protection, whereas NHEJ (non-homologous end-joining) aggravated toxicity of all translational inhibitors. Analysis of specific BER mutants disclosed a strong HygB, zymocin and PaT protective effect of the endonucleases acting on apurinic sites. In cells defective in AP endonucleases, inactivation of the DNA glycosylase Ung1 increased tolerance to ACNases and HygB. In addition, Mag1 specifically contributes to the repair of DNA lesions caused by HygB. Consistent with DNA damage provoked by translation inhibitors, mutation frequencies were elevated upon exposure to both fungal ACNases and HygB. Since polymerase ζ contributed to toxicity in all instances, error-prone lesion-bypass probably accounts for the mutagenic effects. The finding that differently acting inhibitors of protein biosynthesis induce alike cellular responses in DNA repair mutants is novel and suggests the dependency of genome stability on translational fidelity.


CT of abdominal lymphoma after renal transplantation.
Six patients aged 33-68 years developed posttransplant lymphoma of the abdomen an average of 105 months after successful renal transplantation. On computed tomography (CT), five lymphomas presented as bulky masses in intra- (four) or retroperitoneal (one) location. Infiltrative growth into transplanted kidney (three), colon (two), and retroperitoneum (one) resulted in poorly defined margins on CT. Central areas of lower attenuation presumably reflected tumor necrosis. Metastatic deposits in liver (two) and renal transplant (one) were of a focal nature. Prompt radiologic recognition of this serious late complication of renal transplantation is crucial.


They promised this ten years ago. Effects of diabetes news characteristics on patients' perceptions and attitudes towards medical innovations and therapy adherence.
Patients have ever-increasing access to web-based news about hopeful scientific developments that may or may not cure them in the future. Science communication experts agree that the quality of news provision is not always guaranteed. However, literature does not clarify in what way users are actually affected by typical news characteristics such as the news object (described developmental phase of an innovation), the news source (degree of authority), and the news style (degree of language intensification). An online vignette experiment (N = 259) investigated causal relationships between characteristics of news about diabetes innovations and patients' perceptions of future success, their interest in the innovation, and attitudes regarding current therapy adherence. Findings show that descriptions of success in mice led to higher estimations of future success chances than earlier and later developmental phases. Furthermore, news from a nonauthoritative source led to an increased interest in the innovation, and a more negative attitude towards current lifestyle advice. Lastly, the intensification of the language used in news messages showed slight adverse effects on the readers' attitude. These findings, combined with their small effect sizes, support the optimistic view that diabetes patients are generally critical assessors of health news and that future research on this topic should focus on affected fragile subgroups.


Possible insights into metal ion recognition in calcium-binding proteins provided by complexing properties of ligands containing amide oxygen donors.
The formation constants of the ligand N,N,N',N'-tetrakis(carbamoylmethyl)-ethylenediamine suggest that the amide oxygen is a stronger Lewis base in water than the alcoholic oxygen, or water, and that part of the selectivity for Ca2+ over Mg2+ shown by calcium-binding proteins such as calmodulin or annexin may be due to the higher affinity of Ca2+ for the O-donor of the Ca-binding amide groups present in such proteins.


Pulse spectrum analysis, a faster and easier way to predict outcome of sepsis?
In order to provide a faster and easier way for outcome prediction of sepsis, this study aimed to characterize the pattern of arterial pulse spectrum by a rat cecum ligation and puncture (CLP) model and explore whether specific harmonic components of pulse spectrum are associated with the mortality of CLP rats, followed by the comparison of accuracy between these specific variables and IL-6. Nineteen Sprague-Dawley rats receiving CLP were analyzed. Femoral artery of each rat was catheterized for blood pressure recording and blood sampling in the first 24 hours after CLP. The former was for off-line pulse spectrum analysis, and the latter for IL-6 assay. These rats were observed for 3-day mortality after CLP, and were divided into survivor or non-survivor groups. Differences of the hemodynamic profile, IL-6, and changes of the harmonics between the 2 groups were analyzed by using the Mann-Whitney test. Kaplan-Meier curves were constructed to characterize cumulative survival with the best prognostic cutoff point. The characteristic changes of pulse spectrum were different between survivors and non-survivors. The percentage differences of the 2nd harmonic proportion (C2) increased significantly from the 10th hour after CLP, and was higher in the non-survivors. Serum levels of IL-6 were also higher in the non-survivor group. Analyzed by Kaplan-Meier survival curve for 3-day mortality, C2 had a higher accuracy than IL-6 as a predictor. The pulse spectrum analysis may be applied to evaluate the prognosis of CLP rats, and the rapidly and highly elevated C2 harmonic had a strong association with the 3-day mortality of CLP rats.


In vivo spontaneous activity and coital-evoked inhibition of mouse accessory olfactory bulb output neurons.
Little is known about estrous effects on brain microcircuits. We examined the accessory olfactory bulb (AOB) in vivo, in anesthetized naturally cycling females, as model microcircuit receiving coital somatosensory information. Whole-cell recordings demonstrate that output neurons are relatively hyperpolarized in estrus and unexpectedly fire high frequency bursts of action potentials. To mimic coitus, a calibrated artificial vagino-cervical stimulation (aVCS) protocol was devised. aVCS evoked stimulus-locked local field responses in the interneuron layer independent of estrous stage. The response is sensitive to α1-adrenergic receptor blockade, as expected since aVCS increases norepinephrine release in AOB. Intriguingly, only in estrus does aVCS inhibit AOB spike output. Estrus-specific output reduction coincides with prolonged aVCS activation of inhibitory interneurons. Accordingly, in estrus the AOB microcircuit sets the stage for coital stimulation to inhibit the output neurons, possibly via high frequency bursting-dependent enhancement of reciprocal synapse efficacy between inter- and output neurons.


Assessment of neutralizing interleukin-4 effect on CD133 gene expression in colon cancer cell line.
Colorectal cancer may be maintained by cancer stem-like cells (CSCs) that express the cell surface marker CD133. CSCs (CD133+cells) exhibits greater resistance to the chemotherapy and this resistance may be mediated in part by an autocrine response to IL4. The aim of the study was to assess the effect of anti-IL4 antibody alone or in combination with chemotherapy on the CD133 expression andthe tumor growth. We used Caco cell line in our experiments and the samples were as the following; untreated colorectal cell line, cells treated by chemotherapy, cells treated by anti-IL4 antibody in 3doses (2.5, 5, 10μg/ml), cells treatedby combination of chemotherapy and anti-IL4 antibody in 3 doses. Results of our in vitro studies demonstrated that anti-IL4 inhibited growth of Caco cell line in a dose-dependent manner revealing a 32.11% inhibition at the highest concentration (10µg/ml). There was further significant inhibition by combination of anti IL4 and chemotherapy in a dose response manner when compared to group treated by chemotherapy only. These effects were associated with decreased expression of CD133 in tumor cells also. Lastly, anti-IL4 antibody stimulated apoptosis. Our study suggested that neutralizing of IL4 by anti IL4 antibody affect the CD133+ cells may be by increasing their apoptosis. The effects of anti IL4 antibody either, alone or in combination with chemotherapy, inhibited the tumor growth and decreased the viable tumor cells. Furthermore, neutralizing of IL4 increased the efficacy of chemotherapy treatment.


Risk Factors Associated With Hearing Impairment in Infants and Children: A Systematic Review.
The purpose of the present systematic review was to synthesize evidence on associated risk factors of hearing loss (HL) in children. Evidence-based research articles on HL published between January 2013 and December 2022 using PubMed, Cochrane, and Scopus databases were searched. The study included children between zero and three years of age who have permanent bilateral/unilateral HL (BHL/UHL) by employing case-control studies, randomized controlled trials, nonrandomized studies, prospective or retrospective cohort studies, and studies with or without comparison groups. The Newcastle-Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) critical appraisal checklist for longitudinal and cross-sectional studies were used to rate the quality of the chosen studies. The studies that would be considered were reviewed by two independent authors, and a third author was contacted if there was a dispute. A preliminary literature search uncovered 505 articles from the electronic search and 41 studies by hand searching. Duplicate records were eliminated, leaving 432 records. The abstract and title were read, and 340 studies were eliminated. There were 92 articles in total that qualified for full-text screening. Among these, 75 articles were disregarded since they lacked information or failed to assess the risk factors for HL. The qualitative synthesis, therefore, included 17 articles. Most often, cross-sectional study designs were used in the studies that were reviewed, which were then followed by longitudinal studies. Three of the studies that were reviewed used a prospective cohort design. The quality of all the included studies was rated to be good. The current review revealed that the primary statistically significant risk factors for HL included ventilator support; craniofacial anomalies; low birth weight (LBW); forceps delivery; loop diuretics; meningitis; asphyxia; intensive care; consanguinity; sepsis; Apgar scores between 0 and 4 at one minute; toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes (TORCH) infections; and hyperbilirubinemia.


Postexercise oxygen consumption in trained females: effect of exercise duration.
Many research studies report the long-lasting elevation of metabolism following exercise. However, little is known regarding the impact of duration and intensity on this phenomenon, particularly in trained women in whom the time of the menstrual cycle has been controlled. This study examined the effects of a constant walking intensity (70% of maximal oxygen uptake (VO2max)) on the treadmill at various levels of duration (20, 40, and 60 min) on 3-h recovery of oxygen uptake (VO2). Eight trained (mean +/- SD) (VO2max = 47.6 +/- 3.2 ml.kg-1.min-1) females (mean age = 30.2 +/- 5.0 yr, mean weight = 58.7 +/- 7.6 kg, mean height = 165.6 +/- 7.0 cm) participated in the study. Subjects reported to the lab for a maximal oxygen consumption test and returned on four additional occasions (control, 20, 40, 60 min) in random fashion. Treadmill speed and grade were established to yield the appropriate intensity for each subject. Following each exercise bout subjects sat quietly for a 3-h time period. Variables measured included VO2, minute ventilation (VE), respiratory exchange ratio (RER), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and core (rectal) temperature (Tc). Variables were measured each 15 min of recovery. An ANOVA was used to assess differences due to duration. Excess postexercise oxygen consumption (EPOC) was calculated by subtracting the resting VO2 from the absolute VO2 and summing the individual EPOCs during each 3-h postexercise session and comparing these individual values to the preexercise VO2 values. The EPOC was significantly elevated (P < 0.05) in each of the three durations as compared with the control (sitting) and preexercise periods. The total EPOC was significantly higher for the 60-min duration (15.2 l) as compared with either 20-min (8.b l) or 40-min (9.8 l) duration (P < 0.05). This was observed without significant changes in VE, RER, HR, SBP, DBP, or Tc. Additionally, there were no differences during exercise across the three durations in VO2, VE, RER, HR, SBP, DBP, or Tc. These data suggest that exercise duration increases EPOC significantly and that a 60-min duration yields approximately twice the EPOC than either 20 or 40 min.


Quantitative model of diffuse speckle contrast analysis for flow measurement.
Diffuse speckle contrast analysis (DSCA) is a noninvasive optical technique capable of monitoring deep tissue blood flow. However, a detailed study of the speckle contrast model for DSCA has yet to be presented. We deduced the theoretical relationship between speckle contrast and exposure time and further simplified it to a linear approximation model. The feasibility of this linear model was validated by the liquid phantoms which demonstrated that the slope of this linear approximation was able to rapidly determine the Brownian diffusion coefficient of the turbid media at multiple distances using multiexposure speckle imaging. Furthermore, we have theoretically quantified the influence of optical property on the measurements of the Brownian diffusion coefficient which was a consequence of the fact that the slope of this linear approximation was demonstrated to be equal to the inverse of correlation time of the speckle.


Emodin targets mitochondrial cyclophilin D to induce apoptosis in HepG2 cells.
Emodin has demonstrated potent anticancer activity in human hepatocarcinoma cells and animal models, however, the cellular targets of emodin have not been fully defined. Here we report that emodin induces the dysfunction of mitochondria and the apoptosis in HepG2 cells through an enrichment in mitochondria. Specifically, A mitochondrial matrix protein (cyclophilin D, CyPD) is involved in emodin-induced apoptosis, and the inhibitor of CyPD (cyclosporin A) could almost completely suppressing the apoptosis; Moreover, as the expression of CyPD could be effectively inhibited by antioxidant N-acetyl-l-cysteine and epidermal growth factor (the activator of ERK), reactive oxygen species and ERK might be involved in the relevant role of CyPD. A further molecule-docking discloses the existence of three hydrogen-bonds in CyPD-emodin complex. Thus, target localization and CyPD in mitochondria provides an insight into the action of emodin in the treatment of liver cancer.


Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria.
Nephrin, a cytoskeletal protein which localizes to the slit pore of podocytes, may play a role in proteinuria. This study examines the possible relationship between nephrin expression and albuminuria in normotensive and hypertensive diabetic rats. Streptozotocin diabetes was induced in both Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Diabetic and control animals were sacrificed and the kidneys obtained after 8, 16 and 24 weeks. The glomerular filtration rate (GFR) and albuminuria were also measured. Glycaemic control was assessed by measurement of plasma glucose and glycated haemoglobin (HbA1c). Nephrin gene expression was quantitated by real-time polymerase chain reaction (PCR) and localized by in situ hybridization. Nephrin protein expression was localized by immunohistochemistry and quantitated. Following a transient rise at 8 weeks in the diabetic SHR (P < 0.05 versus control SHRs), nephrin gene expression, as determined by real-time PCR, was significantly decreased at 16 and 24 weeks (P < 0.05 versus control SHRs). In situ hybridization confirmed similar changes in nephrin gene expression, which were confined to the glomeruli. This reduction in glomerular nephrin gene expression was associated with increasing albuminuria at 16 and 24 weeks in diabetic SHRs. There were no significant changes in nephrin gene expression, either by real-time reverse transcription polymerase chain reaction or in situ hybridization, observed in normotensive diabetic WKY rats, in the context of much less albuminuria in this group. Immunohistochemistry for nephrin protein revealed a greater depletion in renal nephrin content in SHR than in WKY rats after 24 weeks of diabetes. Reduction in renal nephrin gene and protein expression is closely associated with the development of albuminuria, as observed in an experimental model of diabetes and hypertension.


Unbalanced cryptic translocation der(14)t(9;14)(q34.3;q32.33) identified by subtelomeric FISH.
We investigated a girl with dysmorphic features and moderate developmental delay by subtelomeric FISH (fluorescence in-situ hybridization). We found an unbalanced cryptic translocation, t(9;14)(q34.3;q32.33), resulting in a subtelomeric deletion of 14q and duplication of 9q deriving from a balanced translocation in the mother. A review of the literature suggests that the phenotype of our case is related to the 14 qter deletion, without signs of concomitant partial trisomy 9. The case reinforces the value of subtelomeric screening for genetic counselling.


Analyzing the factors that influence occult metastasis in oral tongue cancer.
We accessed the various clinico-histopathological factors, and their association with occult metastasis (OM) in oral tongue squamous cell carcinoma (OTSCC). One hundred-nine patients with OTSCC were divided into the elective neck dissection (END) group and the watchful waiting (WW) group. Age, sex, T-stage, depth of invasion and differentiation were evaluated to determine the correlation between clinico-histopathological factors and OM. For immunohistochemical analysis, paraffin-embedded blocks of 41 OTSCC specimens were examined with antibodies (VEGF-c, c-Met, and ROR1). The group with tumor thickness of oral tongue cancer ≥3 mm had higher incidence of OM than those with a thickness of <3 mm. The depth of invasion was statistically correlated with OM (P=0.022). Immunohistochemical analysis showed that high expression of VEGF-c (P=0.043), c-Met (P=0.009), and ROR-1 (P=0.003) were statistically correlated with OM. The analysis of these clinico-histopathological and immunohistochemical factors can help to determine neck dissection in clinically negative (cN0) patients.


'Always listen, reflect and learn'.
Jodie Deards, winner of the RCNi Nurse Awards 2017 Commitment to Carers category, earned her degree as part of Australia's first cohort of university-trained nurses in 1993. She came to the UK on a two-year working holiday in 2000 but stayed. After 10 years in the renal unit at Lister Hospital in Stevenage, she took up posts as a community diabetes specialist nurse, practice nurse and community matron. Her current role as carers lead has brought her back to Lister Hospital, part of East and North Hertfordshire NHS Trust.


Psychosocial outcome in a randomized surgical trial for treatment of primary breast cancer.
A study of the differences in the psychosocial effects of mastectomy versus segmentectomy was done on a group of women who were in a prospective randomized protocol for treatment of primary breast cancer. Through questionnaires designed for this study and standardized psychologic tests, women with segmentectomies responded as significantly less anxious, less sad, and more in control of their life events than women with mastectomies. The women with segmentectomies had a statistically more positive sexual and body image than those with mastectomies. The trauma of viewing the surgery was much greater in patients with mastectomies. The concern about cancer recurrence was less in the segmentectomy group. The differences in psychosexual adaptation to mastectomy or segmentectomy and the fears of cancer recurrence were significantly better in the segmentectomy group. The adequacies of cancer therapy was the same for both groups in the national study. This study restresses the importance of the segmentectomy option for women with breast cancer in leading to a better quality of life.


Idiopathic clubfoot treated with the Ponseti method: factors associated with patient follow-up.
Follow-up after treatment with the Ponseti method is important because of the known association be- tween lack of brace wear and recurrence. This study was designed to ascertain factors associated with patients who did not return for the recommended follow-up versus those who did. Between January 1, 2000, and December 31, 2009, 222 patients were treated for idiopathic clubfoot at the New York Ponseti Clubfoot Center at NYU Hospital for Joint Diseases, of which 93 patients (143 feet) were potentially available for follow-up (i.e., ≤ 7 years of age, had not moved, or transferred care to another institution). Attempts were made to contact all patients' parents or guardians by telephone to respond to a survey, which included questions from the Disease Specific Instrument and the Oxford Ankle Foot Questionnaire. Forty-two of the 93 patients (45%) responded. The responder group, those who answered the survey, was compared to the group of non-responders. The responder group was further divided into a returning group (35 out of 42, 83%) and a lost to follow-up group (17%, not followed-up in over a year). A chart review was performed for demographics, Dimeglio/Bensahel and Catterall/Pirani scores, and treatment. When comparing the responder and non- responder groups, the responder group had significantly lower (p < 0.05) Catterall/Pirani scores at initial visit than the non-responder group (5.0 versus 5.5), but otherwise these two groups were similar. Among the responders, 91% or more were very satisfied/satisfied with status and appearance of foot in both lost to follow-up and returning groups. The lost to follow-up group was significantly (p < 0.05) older at the time of the survey (5 years versus 3.7 years), required significantly fewer casts (4.4 versus 5.5), had significantly lower Dimeglio/Bensahel scores at time of the start of foot adbuction orthoses (FAO) (0.0 versus 2.0), and trended toward greater footwear limitations (p = 0.051) compared with the returning group. Number of casts, severity scores at the start of FAO, and footwear limitations are possible factors to differentiate between lost to follow-up and returning patients. This information may help other clubfoot centers provide vigilant outreach and therefore decrease recurrence rate.


Formation of Highly Thermostable Copper-Containing Energetic Coordination Polymers Based on Oxidized Triaminoguanidine.
A series of novel highly thermostable energetic coordination polymers (ECPs), with promising mechanical sensitivity properties, were prepared by an in situ oxidation-coordination reaction of triaminoguanidine hydrochloride with copper nitrate in aqueous solution. The molecular structures and properties of these ECPs could be tuned, by varying the ratios and concentrations of the starting materials. Our ECPs exhibit remarkable thermostability (>390 °C) and very low sensitivity to impact (Im > 98 J). The best-performing material (ECP-5) has a calculated detonation velocity of 8969 m·s(-1) and a decomposition peak temperature of 396.9 °C, demonstrating an outstanding balance between two inherently contradicting properties: high detonation performance and very low sensitivity.


The medial temporal lobe-conduit of parallel connectivity: a model for attention, memory, and perception.
Based on the notion that the brain is equipped with a hierarchical organization, which embodies environmental contingencies across many time scales, this paper suggests that the medial temporal lobe (MTL)-located deep in the hierarchy-serves as a bridge connecting supra- to infra-MTL levels. Bridging the upper and lower regions of the hierarchy provides a parallel architecture that optimizes information flow between upper and lower regions to aid attention, encoding, and processing of quick complex visual phenomenon. Bypassing intermediate hierarchy levels, information conveyed through the MTL "bridge" allows upper levels to make educated predictions about the prevailing context and accordingly select lower representations to increase the efficiency of predictive coding throughout the hierarchy. This selection or activation/deactivation is associated with endogenous attention. In the event that these "bridge" predictions are inaccurate, this architecture enables the rapid encoding of novel contingencies. A review of hierarchical models in relation to memory is provided along with a new theory, Medial-temporal-lobe Conduit for Parallel Connectivity (MCPC). In this scheme, consolidation is considered as a secondary process, occurring after a MTL-bridged connection, which eventually allows upper and lower levels to access each other directly. With repeated reactivations, as contingencies become consolidated, less MTL activity is predicted. Finally, MTL bridging may aid processing transient but structured perceptual events, by allowing communication between upper and lower levels without calling on intermediate levels of representation.


Chromosome-Level Genome Assembly Reveals Dynamic Sex Chromosomes in Neotropical Leaf-Litter Geckos (Sphaerodactylidae: Sphaerodactylus).
Sex determination is a critical element of successful vertebrate development, suggesting that sex chromosome systems might be evolutionarily stable across lineages. For example, mammals and birds have maintained conserved sex chromosome systems over long evolutionary time periods. Other vertebrates, in contrast, have undergone frequent sex chromosome transitions, which is even more amazing considering we still know comparatively little across large swaths of their respective phylogenies. One reptile group in particular, the gecko lizards (infraorder Gekkota), shows an exceptional lability with regard to sex chromosome transitions and may possess the majority of transitions within squamates (lizards and snakes). However, detailed genomic and cytogenetic information about sex chromosomes is lacking for most gecko species, leaving large gaps in our understanding of the evolutionary processes at play. To address this, we assembled a chromosome-level genome for a gecko (Sphaerodactylidae: Sphaerodactylus) and used this assembly to search for sex chromosomes among six closely related species using a variety of genomic data, including whole-genome re-sequencing, RADseq, and RNAseq. Previous work has identified XY systems in two species of Sphaerodactylus geckos. We expand upon that work to identify between two and four sex chromosome cis-transitions (XY to a new XY) within the genus. Interestingly, we confirmed two different linkage groups as XY sex chromosome systems that were previously unknown to act as sex chromosomes in tetrapods (syntenic with Gallus chromosome 3 and Gallus chromosomes 18/30/33), further highlighting a unique and fascinating trend that most linkage groups have the potential to act as sex chromosomes in squamates.


Study of effect of gluten-free diet on vitamin D levels and bone mineral density in celiac disease patients.
Celiac disease (CD) is a multifactorial immune-mediated enteropathy caused by a response to ingested gluten. The current available treatment for CD is lifelong gluten-free diet (GFD). This study was done to see the effect of GFD on Vitamin D levels and bone mass density in celiac patients. A prospective interventional study on newly diagnosed celiac patients was conducted in the Pediatrics department of a tertiary care teaching institute in 2 stages viz. on presentation and after 6 months of GFD. Anthropometric measurements, biochemical investigations, Vitamin D levels, and DEXA scan was done at recruitment and after 6 months of GFD and was analyzed. In newly diagnosed 60 pediatric celiac patients, positive effect of GFD on anthropometry, hemoglobin, Vitamin D levels, DEXA scan parameters was observed. Significant difference was found in Vitamin D levels which increased from baseline 14.85 ± 5.39 to 18.22 ± 5.67 ng/ml after 6 months of GFD (P < 0.05). Significant difference was found in BMD (mean Z-score) which increased from -0.941 ± 0.738 to -0.640 ± 0.60 after 6 months of GFD (P < 0.001). Our study concluded that there is significant increase in vitamin D levels as well as Z-score, bone mass density (BMD) and bone Mass Content (BMC) after 6 months of GFD.


Barriers associated with reduced physical activity in COPD patients.
To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.


The effect of lesions in the mesencephalic reticular formation upon conditioned avoidance responses in rat: I. Lesions of the nucleus commissurae posterioris.
After bilateral symmetric lesions of the n. commissurae posterioris (NCP) hooded rats of the Long-Evans strain did not acquire the conditioned avoidance response (CAR) in a jumping test. The NCP rats were rather unable to find out the escape possibility on the rod hanging in the middle of the apparatus. They did not learn the context between the conditioned stimulus (CS), the unconditioned stimulus (UCS) and the jump. In an Y-maze formation of CAR was even better in NCP rats than in sham-operated controls because of their shorter reaction times and their higher running speed. Their brightness discrimination, on the other hand, was significantly impaired and erroneous runs were only reduced to a low insignificant amount after more than 100 trials. Lesions in the NCP had no severe effects upon preoperatively learnt CARs, but brightness discrimination was still impaired. From these results it may be concluded that NCP plays a role in the formation of goal-directed behaviour depending on external cues and in actual visually guided behaviour.


Machine Learning Models to Interrogate Proteome-wide Cysteine Ligandabilities.
Machine learning (ML) identification of covalently ligandable sites may significantly accelerate targeted covalent inhibitor discoveries and expand the druggable proteome space. Here we report the development of the tree-based models and convolutional neural networks trained on a newly curated database (LigCys3D) of over 1,000 liganded cysteines in nearly 800 proteins represented by over 10,000 X-ray structures as reported in the protein data bank (PDB). The unseen tests yielded 94% AUC (area under the receiver operating characteristic curve), demonstrating the highly predictive power of the models. Interestingly, application to the proteins evaluated by the activity-based protein profiling (ABPP) experiments in cell lines gave a lower AUC of 72%. Analysis revealed significant discrepancies in the structural environment of the ligandable cysteines captured by X-ray crystallography and those determined by ABPP. This surprising finding warrants further investigations and may have implications for future drug discoveries. We discuss ways to improve the models and project future directions. Our work represents a first step towards the ML-led integration of big genome data, structure models, and chemoproteomic experiments to annotate the human proteome space for the next-generation drug discoveries.


Ampicillin vs. placebo for Yersinia pseudotuberculosis infection in children.
For evaluation of the efficacy of early treatment with ampicillin on the clinical course of Yersinia pseudotuberculosis infection in children, 136 patients were randomly assigned to receive either ampicillin or placebo. Subjects were those who were diagnosed as having Kawasaki syndrome and those who satisfied three of the following four criteria: fever; rash; abdominal symptoms; and a history of ingestion of untreated drinking water. Fifty-six patients had evidence of Y. pseudotuberculosis infection bacteriologically and/or serologically. Twenty-six were assigned to placebo and 28 to ampicillin. Ampicillin therapy did not show a significant benefit in shortening the duration of fever, diarrhea and abdominal pain or in preventing rash, erythema nodosum and acute renal failure. After 5 days of treatment none of the patients in the ampicillin group excreted the organism in the stool whereas 19 (90%) of 21 in the placebo group did (P less than 0.001). Ampicillin did not show a clinical benefit but reduced the fecal excretion of the organism.


Urinary Infections in Patients with Catheters in the Upper Urinary Tract: Microbiological Study.
Infections related to catheters in the upper urinary tract (CUUT) are associated with specific characteristics. A prospective observational study was carried out from 2012 to 2015 to evaluate infections in patients with CUUT. A total of 209 infections were included (99 with double-J, 81 with nephrostomy, and 29 with internal/external nephroureteral stents). Among nephrostomy tube carriers, the most frequently isolated microorganisms were Pseudomonas and Enterococcus. In those with an internal/external nephroureteral stent, Klebsiella was the most common, and 57.1% were extended-spectrum beta-lactamase-producing Klebsiella. In double-J carriers, Escherichia coli and Enterococcus were the most common microorganisms. Multiple-drug resistance (MDR) microorganisms were isolated in 28.6, 47.1, and 58.3% of patients with double-J, nephrostomy, and internal-external nephroureteral stents. A percutaneous CUUT (p = 0.005) and immunosuppression (p = 0.034) were risk factors for MDR microorganisms. Non-E. coli bacteria are commonly isolated in patients with CUUT. MDR microorganisms are frequent, mainly in percutaneous approach or immunosuppression.


Epigenetic Dysregulation Observed in Monosomy Blastocysts Further Compromises Developmental Potential.
Epigenetic mechanisms such as DNA methylation regulate genomic imprinting and account for the distinct non-equivalence of the parental genomes in the embryo. Chromosomal aneuploidy, a major cause of infertility, distorts this highly regulated disparity by the presence or absence of chromosomes. The implantation potential of monosomy embryos is negligible compared to their trisomy counterparts, yet the cause for this is unknown. This study investigated the impact of chromosomal aneuploidy on strict epigenetically regulated domains, specifically imprinting control regions present on aneuploid chromosomes. Donated cryopreserved human IVF blastocysts of transferable quality, including trisomy 15, trisomy 11, monosomy 15, monosomy 11, and donor oocyte control blastocysts were examined individually for DNA methylation profiles by bisulfite mutagenesis and sequencing analysis of two maternally methylated imprinting control regions (ICRs), SNRPN (15q11.2) and KCNQ1OT1 (11p15.5), and one paternally methylated imprinting control region, H19 (11p15.5). Imprinted genes within the regions were also evaluated for transcript abundance by RT-qPCR. Overall, statistically significant hypermethylated and hypomethylated ICRs were found in both the trisomy and monosomy blastocysts compared to controls, restricted only to the chromosome affected by the aneuploidy. Increased expression was observed for maternally-expressed imprinted genes in trisomy blastocysts, while a decreased expression was observed for both maternally- and paternally-expressed imprinted genes in monosomy blastocysts. This epigenetic dysregulation and altered monoallelic expression observed at imprinting control regions in aneuploid IVF embryos supports euploid embryo transfer during infertility treatments, and may specifically highlight an explanation for the compromised implantation potential in monosomy embryos.


Ready-to-use introduction schedules for first exposure to allergenic foods in children at home.
The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised. The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods. Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic. Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions. The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.


Prevalence and risk factor of renal dysfunction induced by bacterial infection other than spontaneous bacterial peritonitis in patients with cirrhosis.
Deterioration of renal function in cirrhotic patients with spontaneous bacterial peritonitis (SBP) is a predictor for inhospital mortality. However, the clinical significance of renal dysfunction during bacterial infection other than SBP is unknown. To investigate the prevalence and clinical significance of renal dysfunction due to bacterial infections other than SBP in patients with liver cirrhosis. Retrospective data from in-patients with bacterial infections other than SBP were analyzed. Eighty-two patients were recruited for the analysis. Infection was located in urinary tract (41.5%), pneumonia (34.1%), biliary tract (3.7%), cellulitis (6.1%), gastrointestinal tract (4.9%) and bacteremia of unknown origin (9.7%). Renal dysfunction developed in 40 patients (48.8%), of which 13 patients had irreversible renal dysfunction. In the univariate and multivariate analysis, the initial MELD score, neutrophil count, bilirubin, and blood pressure were significant risk factors for renal dysfunction. The prevalence of renal dysfunction during bacterial infection other than SBP in patients with liver cirrhosis was 48.8%, and its development was related to the severity of the liver disease. Occurrence of irreversible renal dysfunction seemed to affect the prognosis of these patients.


Decellularization of Large Tendon Specimens: Combination of Manually Performed Freeze-Thaw Cycles and Detergent Treatment.
Reliable decellularization techniques applicable to tendon tissue play a critical role in the field of current tissue engineering. Particularly, an application as three-dimensional culture model for in vitro research and translational approaches to establish graft-based tendon repair as a routine clinical tool represent two main application fields for decellularized tendon scaffolds. Considering methodological issues of tendon decellularization, one of the major challenges lies in the preservation of the tendon-specific extracellular matrix (ECM) architecture to reflect natural tissue characteristic as best as possible. Concurrently, further requirements for high-quality decellularized biological tendon scaffolds include not only the reduction of resident cells, but also an ensured cytocompatibility.To date, a large number and a wide variety of decellularization protocols for natural tendon tissue have already been investigated and usually, physical as well as chemical and/or enzyme-based treatments are used for the purpose of decellularization. However, to the best of our knowledge, there is a lack of evidence-based protocols for the processing of full-thickness large tendon samples, such as the equine flexor tendons.Therefore, the here presented protocol describes a reliable procedure to decellularize equine superficial digital flexor tendons by using a combined treatment of physical decellularization in the form of repetitive freeze-thaw cycles, and of chemical decellularization with the non-ionic detergent Triton X-100. The decellularization effectiveness evaluated by reduction of cell and DNA content, the influence of decellularization on the morphology of the tendon extracellular matrix (ECM) as well as the cytocompatibility of the decellularized tendon scaffolds obtained have been investigated previously. Based on this previous study, the here present protocol is an effective procedure, particularly applicable for large tendon specimens.


A GCSFR/CSF3R zebrafish mutant models the persistent basal neutrophil deficiency of severe congenital neutropenia.
Granulocyte colony-stimulating factor (GCSF) and its receptor (GCSFR), also known as CSF3 and CSF3R, are required to maintain normal neutrophil numbers during basal and emergency granulopoiesis in humans, mice and zebrafish. Previous studies identified two zebrafish CSF3 ligands and a single CSF3 receptor. Transient antisense morpholino oligonucleotide knockdown of both these ligands and receptor reduces neutrophil numbers in zebrafish embryos, a technique widely used to evaluate neutrophil contributions to models of infection, inflammation and regeneration. We created an allelic series of zebrafish csf3r mutants by CRISPR/Cas9 mutagenesis targeting csf3r exon 2. Biallelic csf3r mutant embryos are viable and have normal early survival, despite a substantial reduction of their neutrophil population size, and normal macrophage abundance. Heterozygotes have a haploinsufficiency phenotype with an intermediate reduction in neutrophil numbers. csf3r mutants are viable as adults, with a 50% reduction in tissue neutrophil density and a substantial reduction in the number of myeloid cells in the kidney marrow. These csf3r mutants are a new animal model of human CSF3R-dependent congenital neutropenia. Furthermore, they will be valuable for studying the impact of neutrophil loss in the context of other zebrafish disease models by providing a genetically stable, persistent, reproducible neutrophil deficiency state throughout life.


Ethical challenges of researchers in qualitative studies: the necessity to develop a specific guideline.
Considering the nature of qualitative studies, the interaction between researchers and participants can be ethically challenging for the former, as they are personally involved in different stages of the study. Therefore, formulation of specific ethical guidelines in this respect seems to be essential. The present paper aimed to discuss the necessity to develop explicit guidelines for conducting qualitative studies with regard to the researchers' role. For this purpose, a literature review was carried out in domestic and international databases by related keywords. Health care providers who carry out qualitative research have an immense responsibility. As there is no statistical analysis in qualitative studies, the researcher has to both evaluate what he or she observes and to interpret it. Providing researchers with the necessary skills and applying stringent supervision can lead to better extraction of reliable information from qualitative studies. This article presents a debate in order to illustrate how researchers could cover the ethical challenges of qualitative studies and provide applicable and trustworthy outcomes. Researchers face ethical challenges in all stages of the study, from designing to reporting. These include anonymity, confidentiality, informed consent, researchers' potential impact on the participants and vice versa. It seems of paramount importance that health care providers, educators and clinicians be well informed of all the different aspects of their roles when acting as qualitative researchers. Hence, these adroit roles need to be well defined, and the use of practical guidelines and protocols in all stages of qualitative studies should be encouraged.


Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.
Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.


Optical, electrochemical, and magnetic properties of pyrrole- and thiophene-bridged 5,15-diazaporphyrin dimers.
The first examples of pyrrole- and thiophene-bridged 5,15-diazaporphyrin (DAP) dimers are prepared through Stille coupling reactions of nickel(II) and copper(II) complexes of 3-bromo-10,20-dimesityl-5,15-diazaporphyrin (mesityl=2,4,6-trimethylphenyl) with the respective 2,5-bis(tributylstannyl)heteroles. The effects of the heterole spacers and meso nitrogen atoms on the optical, electrochemical, and magnetic properties of the DAP dimers are investigated by UV/Vis absorption spectroscopy, density functional theory calculations, magnetic circular dichroism spectroscopy, cyclic voltammetry, and EPR spectroscopy. The heterole spacers are found to have a significant impact on the electronic transitions over the entire π-system. In particular, the pyrrole-bridged DAP dimers exhibit high light-harvesting potential in the low-energy visible/near-infrared region owing to the intrinsic charge-transfer character of the lowest excitation.


Identification of reproducible low mass SELDI protein profiles specific to cisplatin resistance in human ovarian cancer cells.
Platinum compounds are the most effective drugs in the fight against ovarian cancer. Unfortunately, many ovarian tumors are not eradicated by chemotherapy due to the emergence of drug-resistant clones during therapy, and hence 5-year survival rate of women afflicted with this disease is just 18%. In the continued absence of an effective early detection test for ovarian cancer, there is a considerable need to develop treatment strategies that can either circumvent (e.g. gene therapy) or prevent the development of platinum resistance. A prerequisite for the development of such treatments is a detailed knowledge of factors that confer tumor cell resistance to platinum compounds. We have used surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS or SELDI) to identify low mass proteins that are uniquely expressed in ovarian tumor cells that are platinum-resistant. Only two polypeptide peaks (m/z 5041 and 7324) were consistently altered following the induction of cisplatin resistance in the OAW42 and 2780 cell lines. These peaks appear to be specific to cisplatin resistance as they are not altered in the same manner in a melphalan-resistant variant of OAW42. The exact identity of the polypeptide peaks is unknown, but appears to be unrelated to changes in several proteins that have been historically associated with cisplatin resistance. These data suggest that SELDI-based proteomic profiling may be useful in monitoring the emergence of cisplatin-resistant tumor cell clones.


Ludangshen oral liquid for treatment of convalescent COVID-19 patients: a randomized, double-blind, placebo-controlled multicenter trial.
To explore the effect of Ludangshen oral liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method. 200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen oral liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study. 8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P < 0.05), while there was no significant difference in distention (P > 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P < 0.05), as well as the resolution rates (P < 0.05) except for shortness of breath (P > 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group. The study suggested that two weeks of Ludangshen oral liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms.


Electrochemical control of emission enhancement in solid-state nitrogen-doped carbon quantum dots.
Because of their excellent optical and electrical properties, doped carbon quantum dots (CQDs) are expected to be used in novel film optoelectronic devices such as light-emitting diodes and solar cells. However, these device advancements are currently hindered by the elusive photophysical process of doped CQDs in solid-state films. Here, the optical properties of nitrogen-doped CQD (N-CQD) films are studied using spectro-electrochemical (SEC) methods. A distinctive photoluminescence (PL) enhancement phenomenon is observed, in which the PL intensity of the N-CQD film can be increased in both positive and negative electrochemical potential sweeps. The effect of positive potential on PL enhancement is greater (∼340% at +1.4 V), while that of negative potential is slightly weaker (∼10% at -1.4 V). To the best of our knowledge, no similar brightening process has been reported in all previous SEC studies on a variety of QDs, wherein the emission intensity can only exhibit enhancement under positive or negative potential at most. We propose that the above PL brightening is related to the weakened π-π stacking effect after electrochemical charge injection and nitrogen doping plays a crucial role in it. Finally, a low hysteresis reversible electrochemistry regulation of the PL spectrum can be achieved by increasing electrolyte fluidity with argon gas bubbling to reduce local charge aggregation.


Combinatorial approach to hepadnavirus-like particle vaccine design.
The particulate hepatitis core protein (HBcAg) represents an efficient carrier platform with many of the characteristics uniquely required for the delivery of weak immunogens to the immune system. Although the HBcAg is highly immunogenic, the existing HBcAg-based platform technology has a number of theoretical and practical limitations, most notably the "preexisting immunity" and "assembly" problems. To address the assembly problem, we have developed the core protein from the woodchuck hepadnavirus (WHcAg) as a new particulate carrier platform system. WHcAg appears to tolerate insertions of foreign epitopes at a greater number of positions than HBcAg. For example, both within the external loop region and outside the loop region a total of 17 insertion sites were identified on WHcAg. Importantly, the identification of an expanded number of insertion sites was dependent on additional modifications to the C terminus that appear to stabilize the various internal insertions. Indeed, 21 separate C-terminal modifications have been generated that can be used in combination with the 17 insertion sites to ensure efficient hybrid WHcAg particle assembly. This combinatorial technology is also dependent on the sequence of the heterologous insert. Therefore, the three variables of insert position, C terminus, and epitope sequence are relevant in the design of hybrid WHcAg particles for vaccine purposes.


[Biomechanical aspects of cervical trauma].
The biomechanical expert opinion on the injury mechanism is necessary in few cases only. However, the judgement of these cases is extremely compromised if mechanically wrong terms are introduced in the clinical report. Since the injury mechanism in the neck is very complex the clinical physician should concentrate on the clinical findings familiar to him; usually the clinician lacks technical case documentation and specific training in injury biomechanics. The relevant mechanisms of neck injuries are an indirect trauma induced by a) a head contact leading to compression, hyperflexion, hyperextension and/or hypertranslation and b) a non-head-contact mechanism (hyperflexion or hyperextension, hypertranslation, acceleration). A non-contact mechanism occurs e.g. during a rear end impact without head restraint (hyperextension) or a frontal collision of a belted occupant (hyperflexion) without head impact. The term "whiplash" is misleading and incorrect: It presumes a virtually non existing two phase movement back and forth (or vice versa) like during the development of the crack of the whip. Secondly, it mixes the physical criterion mechanism with the anatomical or morphological criterion injury e.g. distortion, sprain etc. A (head)-contact mechanism is due to a corresponding momentum exerted from the head on the neck. Again, the anatomical or morphological terms are equal, but the mechanism is different. During a contact mechanism as well as during a non-contact mechanism not only a hyperflexion or a hyperextension can occur; in the first phase of the impact also a shearing force between the upper vertebral bodies (CO-C2) may load the intervertebral structures by hypertranslation.


Global expression analysis of two-component system regulator genes during Mycobacterium tuberculosis growth in human macrophages.
In the Mycobacterium tuberculosis H37Rv genome, there are 11 paired two-component regulatory system genes, two orphan histidine kinase genes, and six orphan response regulator genes. Expression of the 17 response regulator genes and the two orphan histidine kinase genes during growth of M. tuberculosis in human peripheral blood monocyte-derived macrophages has been analyzed by using cDNA mixtures prepared by the selective capture of transcribed sequences (SCOTS) technique. SCOTS probes were prepared from cDNA obtained from M. tuberculosis grown for 18, 48, and 110 h in human macrophages. Based on expression profiles, the regulatory genes were assigned to three categories: (i) constitutively expressed during growth in macrophages (three genes); (ii) differentially expressed during growth in macrophages (nine genes) and (iii) no detectable expression during growth in macrophages (seven genes).


Implantation of a gelatin-sponge as a model for effector recruitment. Tumor growth inhibition by T-lymphocytes recovered from a site of tumor rejection.
Nylon-wool-eluted lymphocytes, isolated from a site of tumor rejection in Balb/c mice expressing concomitant tumor immunity, were examined for their ability to inhibit the growth of the EMT6 tumor. Tumor growth inhibition was monitored after co-inoculation of lymphocytes and tumor cells into naive mice in a Winn-type adoptive-transfer assay. A pre-implanted gelatin sponge was employed to capture the tumor-infiltrating lymphocytes. Mice harboring primary tumors were implanted 8 days later with gelatin sponges. The pre-implanted sponges were then inoculated with a secondary tumor challenge 2 days after implantation of the sponge (i.e. 10 days after primary tumor challenge). On day 17 (7 days after secondary tumor challenge), the immune sponges were retrieved, digested in collagenase and the T lymphocytes were isolated using a nylon-wool column. Blank sponges (lacking tumor cells), obtained from primary-tumor-bearing or non-tumor-bearing animals, were included for comparison. The data showed that T lymphocytes isolated from immune sponges inhibited tumor growth while T lymphocytes recovered from blank sponges did not. At an effector:target (E:T) ratio of 10:1 the lymphocytes from the immune sponges were able to prevent totally the growth of tumors in all cases (100% inhibition). This ability was reduced (60% inhibition) at an E:T ratio of 1:1. Comparison of the antitumor activities of the immune-sponge-derived cells with those from the spleen of the same animal revealed the superiority of the former. Depletion of immune-sponge-derived cells with anti-Thy1.2, anti-Lyt2.2 or anti-L3T4 and complement resulted in a marked decrease in tumor-inhibitory activity. These results indicate that T lymphocytes, expressing Thy1.2, Lyt2.2 or L3T4 antigens, are involved in conferring protection to Balb/c mice against the EMT6 tumor.


Participant Evaluation of Twelve-Step Group Linkage for Jailed Women With Alcohol Use Disorder.
Jailed women are an underserved population with elevated rates of alcohol use disorders. Brief jail stays make delivery of case management and traditional alcohol treatment impractical yet women face significant reentry challenges with few help resources. Accounting for these challenges, linking jailed women with a twelve-step program volunteer for a one-on-one meeting has been hypothesized to provide a means of support that can transition with women after jail discharge. In-jail meetings are theoretically consistent with the common twelve-step practice of conducting twelve-step calls. The acceptability and content of a one-on-one, in-jail meeting with a twelve-step volunteer were explored using qualitative data collected through interviews with 72 women directly following their in-jail volunteer meeting. Participants found the meeting to be acceptable and to contain many useful elements, and content was in line with the standard twelve-step calls. Findings are encouraging both for the potential utility of the intervention and for dissemination of similar linkage approaches.


[Ultrasound in diagnosis of benign and malignant liver tumors].
Sonography has a high sensitivity in diagnosing circumscript lesions in the liver when modern machines are used by a skilled examiner. The exact analysis of the sonographic imaging characteristics allows definite diagnosis in the majority of cases. The high prevalence of benign liver tumors has to be considered. It is substantiated by an evaluation of 731 own patients. The characteristics of the most important circumscribed liver lesions are presented and suggestions for the diagnostic work-up are provided.


Tick-Borne Myopericarditis With Positive Anaplasma, Lyme, and Epstein Barr Virus (EBV) Serology: A Case Report.
Myopericarditis has been reported only rarely in those with anaplasmosis and is typically difficult to diagnose. Lyme carditis can also be difficult to diagnose as it is relatively rare but potentially fatal and usually has nonspecific manifestations. We are presenting a 61-year-old male patient who presented in New Jersey, United States with unremitting fever, chills, and myalgia for two weeks along with nausea, vomiting, and diarrhea. Investigations were suggestive of perimyocarditis as was indicated by diffuse ST segment elevation on electrocardiography (EKG) with the presence of small pericardial effusion on echocardiography. A mild troponin leakage was also seen. This progressed to septic shock that required vasopressor therapy. Further history-taking revealed recent tick exposure and prompted empirical initiation of doxycycline. This proved to be successful with fever defervescence and clinical improvement. Serological tests confirmed both acute Lyme and anaplasma infections along with positive serology of Epstein Barr virus (EBV). This case highlights an uncommon presentation of carditis in acute Lyme and anaplasma infections with the associated false-positive serology of EBV.


High-Loading Crystals of Tetraaryladamantanes and the Uptake and Release of Aromatic Hydrocarbons from the Gas Phase.
Recently, a tetraphenyladamantane octamethylether was shown to encapsulate a wide range of small molecules in its crystals. Uptake and release from the liquid phase were demonstrated, and crystalline inclusion complexes were prepared that act as formulation for obnoxious reagents. However, fewer than two equivalents of guest molecules were found within the crystal structures. Here we report the synthesis of 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO) and twelve X-ray crystal structures that contain up to 3.5 equivalents of guest molecules. After crystallization and drying, TEO gives a material that absorbs 30 wt % of p-xylene reversibly through the gas phase, and releases it again at 55 °C, suggesting that it may be used for the capture and release of aromatic hydrocarbons.


Effects of interrupting the renin-angiotensin system on sodium excretion in man.
1. Twelve normal volunteers were studied on 2 separate days, having taken a range of diets providing 50-300 mmol sodium per day for 3 days and having been dehydrated overnight. Each volunteer received a background intravenous infusion of arginine vasopressin (5 x 10(-7) i.u. kg-1 min-1) on both days, and also received 6 mg captopril orally on one day and a placebo tablet on the other. The ensuing changes in arterial pressure, and in urinary solute and solute-free water excretion were recorded. 2. Captopril did not significantly alter arterial pressure. It increased the rate of excretion of sodium but not of potassium, and it did not significantly change urinary osmolality or creatinine clearance. 3. Captopril increased the rate of solute-free water reabsorption and did so in direct proportion to its effect of increasing sodium excretion. 4. A further twelve normal, dehydrated volunteers on free diets were studied on each of 2 days, after taking 500 mg lithium carbonate on the previous evening. On each day, they also received a loading dose and maintenance infusion of inulin. On one day they received 50 mg captopril orally, and, on the other, they received a placebo tablet. The arterial pressure, urinary excretion of electrolytes, and inulin clearance were recorded. 5. Captopril increased the rates of excretion of sodium, lithium and potassium, but there were no significant changes in inulin clearance or arterial pressure. 6. The natriuretic effect of captopril in either group of twelve volunteers was not significantly less in those volunteers who were already excreting more sodium, at least over the range of dietary sodium loading to which the volunteers were subjected. 7. Six normal volunteers were studied on a further 2 days, having taken a diet supplying 30 mmol sodium per day for 3 days and being dehydrated overnight. Each volunteer received a background intravenous infusion of arginine vasopressin (5 x 10(-7) i.u. kg-1 min-1) on both days and also received an intravenous infusion of saralasin acetate (50 ng kg-1 min-1) plus carrier on one day and carrier alone on the other. The ensuing changes in arterial pressure, and in urinary solute and solute-free water excretion were recorded. 8. There was a small but significant fall in systolic arterial pressure during the infusion of saralasin.(ABSTRACT TRUNCATED AT 400 WORDS)


Hot Charge Carrier Transmission from Plasmonic Nanostructures.
Surface plasmons have recently been harnessed to carry out processes such as photovoltaic current generation, redox photochemistry, photocatalysis, and photodetection, all of which are enabled by separating energetic (hot) electrons and holes-processes that, previously, were the domain of semiconductor junctions. Currently, the power conversion efficiencies of systems using plasmon excitation are low. However, the very large electron/hole per photon quantum efficiencies observed for plasmonic devices fan the hope of future improvements through a deeper understanding of the processes involved and through better device engineering, especially of critical interfaces such as those between metallic and semiconducting nanophases (or adsorbed molecules). In this review, we focus on the physics and dynamics governing plasmon-derived hot charge carrier transfer across, and the electronic structure at, metal-semiconductor (molecule) interfaces, where we feel the barriers contributing to low efficiencies reside. We suggest some areas of opportunity that deserve early attention in the still-evolving field of hot carrier transmission from plasmonic nanostructures to neighboring phases.


Upcycling of Electroplating Sludge into Ultrafine Sn@C Nanorods with Highly Stable Lithium Storage Performance.
Sn-based anode materials have become potential substitutes for commercial graphite anode due to their high specific capacity and good safety. In this paper, ultrafine Sn nanoparticles embedded in nitrogen and phosphorus codoped porous carbon nanorods (Sn@C) are obtained by carbonizing bacteria that adsorb the Sn electroplating sludge extracting solution. The as-prepared Sn@C rod-shaped composite exhibits superior electrochemical Li-storage performances, such as a reversible capacity of approximate 560 mAh/g at 1 A/g and an ultralong cycle life exceeding 1500 cycles, with approximately no capacity decay. The ultrastable structure of the Sn@C was revealed using in situ transmission electron microscope at the nanoscale and indicated that the Sn@C composite could restrict the volume expansion of Sn nanoparticles during the lithiation/delithiation cycles. This work provides a new insight into addressing the electroplating sludge and designing novel lithium ion battery anodes.


Vaccination timing of low-birth-weight infants in rural Ghana: a population-based, prospective cohort study.
To investigate delays in first and third dose diphtheria-tetanus-pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. We used data from a large, population-based vitamin A trial in 2010-2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0-2.4 kg; 1.5-1.9 kg; and < 1.5 kg) with infants weighing ≥ 2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). Compared with non-low-birth-weight infants (n = 18 979), those with low birth weight (n = 3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43-0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50-0.80). Infants weighing 1.5-1.9 kg (n = 386) had vaccination rates approximately 25% lower than infants weighing ≥ 2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays.


[Macroprolactinemia, a variety of hyperprolactinemia. Apropos of 5 cases].
Macroprolactinemia, due to increased circulating levels of large molecular weight forms of prolactin, results in elevated level of immuno-reactive prolactin. The big variants have only weak biological activity; thus macroprolactinemia appears as a case of hyperprolactinemia without clinical significance as demonstrated by the five patients described. The diagnosis is based upon chromatography which separates the hormone and its variants. This disorder produces a pitfall in the diagnostic evaluation of hyperprolactinemia.