Mechanisms of HIV and nucleoside reverse transcriptase inhibitor injury to mitochondria.
Available evidence suggests that a number of important clinical events in individuals with HIV infection are related to mt dysfunction. Several factors may contribute to the development of these events and the tissue(s) in which the event occurs. Some individuals are likely to have important genetic predispositions for mt disease, which may be unmasked by the presence of HIV infection or the introduction of NRTI antiretrovirals. HIV infection per se is associated with reduction in mtDNA content and changes in mt morphology and function, which in some cases leads to clinical events such as myopathy or peripheral neuropathy. NRTI antiretrovirals may impact mtDNA content and function through a number of different mechanisms and have been demonstrated to be causative of a number of clinical toxicities. In in vitro and in clinical studies, newer nucleoside and nucleotides agents such as lamivudine, emtricitabine, abacavir and tenofovir appear to be much weaker inhibitors of mtDNA polymerase-gamma or other mt functions, and appear to be associated with a lower risk of events thought to be related to mt toxicity. Simple, non-invasive tests for mt function are not available at present in the clinical routine, and assays of mtDNA content in blood cells may miss key aspects of mt function, require careful sample handling and may not reflect events occurring in other tissues. There remains a need for the development of rapid, cheap and clinically applicable assays that would enable the prediction of increased likelihood of mt events.


Postnatal development of pyrogenic sensitivity in guinea pigs.
Despite evidence of thermoregulatory ability from birth, neonates generally are unable to develop fever when challenged with endotoxin. This could be due to their small capacity for heat storage. To test this possibility, the pyrogenicity of S. enteritidis endotoxin (2 mug/kg, iv) was measured at both room (Ta = 25 degrees C) and neutral (Tn = 29-33 degrees C, depending on age) temperatures in 0- to 32-day-old unanesthetized guinea pigs, reared from birth at about 24 degrees C. Control guinea pigs received sterile saline injections in concurrent experiments. Shivering, O2 uptake, and colonic (Tre) and subcutaneous [over the interscapular fat pad (Tbat) and the sacrospinalis muscle (Tsc)] temperatures were recorded continuously for 4 h after injection. Endotoxin generally produced no febrile responses at both ambient temperaturess rises in animals aged 8 or more days; Tbat increased before the other sites in the 8- and 16-day-old animals, and shivering did not occur; by 32 days of age, however, Tbat no longer increased first, and there was shivering. In Tn significant febrile rises were not evident until 32 days of age; control temperatures, however, were elevated during this exposure as compared to at Ta. These results showed therefore that pyrogenic sensitivity is not apparent in guinea pigs during the first postnatal week; thereafter fever responses are evocable, but their detection may be masked by environmentally produced changes in body temperature. The data also indicated that the site of the heat production underlying, in part, endotoxic fevers gradually shifts from brown fat so skeletal muscle during the first month of life.


Guard Cell Starch Degradation Yields Glucose for Rapid Stomatal Opening in Arabidopsis.
Starch in Arabidopsis (Arabidopsis thaliana) guard cells is rapidly degraded at the start of the day by the glucan hydrolases α-AMYLASE3 (AMY3) and β-AMYLASE1 (BAM1) to promote stomatal opening. This process is activated via phototropin-mediated blue light signaling downstream of the plasma membrane H+-ATPase. It remains unknown how guard cell starch degradation integrates with light-regulated membrane transport processes in the fine control of stomatal opening kinetics. We report that H+, K+, and Cl- transport across the guard cell plasma membrane is unaltered in the amy3 bam1 mutant, suggesting that starch degradation products do not directly affect the capacity to transport ions. Enzymatic quantification revealed that after 30 min of blue light illumination, amy3 bam1 guard cells had similar malate levels as the wild type, but had dramatically altered sugar homeostasis, with almost undetectable amounts of Glc. Thus, Glc, not malate, is the major starch-derived metabolite in Arabidopsis guard cells. We further show that impaired starch degradation in the amy3 bam1 mutant resulted in an increase in the time constant for opening of 40 min. We conclude that rapid starch degradation at dawn is required to maintain the cytoplasmic sugar pool, clearly needed for fast stomatal opening. The conversion and exchange of metabolites between subcellular compartments therefore coordinates the energetic and metabolic status of the cell with membrane ion transport.


Roussy-Lévy syndrome is a phenotypic variant of Charcot-Marie-Tooth syndrome IA associated with a duplication on chromosome 17p11.2.
The Roussy-Lévy syndrome (MIM #180800) was described in 1926 as a disorder presenting with pes cavus and tendon areflexia, distal limb weakness, tremor in the upper limbs, gait ataxia and distal sensory loss. We report a family with affected members in four generations, showing these clinical signs of Roussy-Lévy syndrome and a partial duplication at chromosome 17p11.2. This genetic defect is commonly found in patients with the hypertrophic form of the Charcot-Marie-Tooth syndrome. Our finding provides evidence against the Roussy-Lévy syndrome as a distinct entity but suggests a close relation with the Charcot-Marie-Tooth syndrome. What causes the additional features of gait ataxia and essential tremor needs further clarification.


Habituation After Deep Brain Stimulation in Tremor Syndromes: Prevalence, Risk Factors and Long-Term Outcomes.
Deep brain stimulation (DBS) of the thalamus is an effective treatment for medically refractory essential, dystonic and Parkinson's tremor. It may also provide benefit in less common tremor syndromes including, post-traumatic, cerebellar, Holmes, neuropathic and orthostatic tremor. The long-term benefit of DBS in essential and dystonic tremor (ET/DT) often wanes over time, a phenomena referred to as stimulation "tolerance" or "habituation". While habituation is generally accepted to exist, it remains controversial. Attempts to quantify habituation have revealed conflicting reports. Placebo effects, loss of micro-lesional effect, disease related progression, suboptimal stimulation and stimulation related side-effects may all contribute to the loss of sustained long-term therapeutic effect. Habituation often presents as substantial loss of initial DBS benefit occurring as early as a few months after initial stimulation; a complex and feared issue when faced in the setting of optimal electrode placement. Simply increasing stimulation current tends only to propagate tremor severity and induce stimulation related side effects. The report by Paschen and colleagues of worsening tremor scores in the "On" vs. "Off" stimulation state over time, even after accounting for "rebound" tremor, supports the concept of habituation. However, these findings have not been consistent across all studies. Chronic high intensity stimulation has been hypothesized to induce detrimental plastic effects on tremor networks, with some lines of evidence that DT and ET may be more susceptible than Parkinson's tremor to habituation. However, Tsuboi and colleague's recent longitudinal follow-up in dystonic and "pure" essential tremor suggests otherwise. Alternatively, post-mortem findings support a biological adaption to stimulation. The prevalence and etiology of habituation is still not fully understood and management remains difficult. A recent study reported that alternating thalamic stimulation parameters at weekly intervals provided improved stability of tremor control consistent with reduced habituation. In this article the available evidence for habituation after DBS for tremor syndromes is reviewed; including its prevalence, time-course, possible mechanisms; along with expected long-term outcomes for tremor and factors that may assist in predicting, preventing and managing habituation.


Intracortical brain-computer interfaces for improved motor function: a systematic review.
In this systematic review, we address the status of intracortical brain-computer interfaces (iBCIs) applied to the motor cortex to improve function in patients with impaired motor ability. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for Systematic Reviews. Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and the Effective Public Health Practice Project (EPHPP) were used to assess bias and quality. Advances in iBCIs in the last two decades demonstrated the use of iBCI to activate limbs for functional tasks, achieve neural typing for communication, and other applications. However, the inconsistency of performance metrics employed by these studies suggests the need for standardization. Each study was a pilot clinical trial consisting of 1-4, majority male (64.28 %) participants, with most trials featuring participants treated for more than 12 months (55.55 %). The systems treated patients with various conditions: amyotrophic lateral sclerosis, stroke, spinocerebellar degeneration without cerebellar involvement, and spinal cord injury. All participants presented with tetraplegia at implantation and were implanted with microelectrode arrays via pneumatic insertion, with nearly all electrode locations solely at the precentral gyrus of the motor cortex (88.88 %). The development of iBCI devices using neural signals from the motor cortex to improve motor-impaired patients has enhanced the ability of these systems to return ability to their users. However, many milestones remain before these devices can prove their feasibility for recovery. This review summarizes the achievements and shortfalls of these systems and their respective trials.


Characteristics of Adsorption/Desorption Process on Dolomite Adsorbent in the Copper(II) Removal from Aqueous Solutions.
The removal of hazardous heavy metals that have been released into the environment due to industrial activities has become an important issue in recent years. The presented study concerned the removal of copper(II) ions from aqueous solutions using dolomites. Dolomite is a very attractive adsorbent due to its wide availability, low cost, good adsorption, and environmental compatibility. The paper describes the properties of D-I and D-II dolomites from two different open-cast mines in Poland. The properties of natural adsorbents were determined based on point of zero charges (PZC), elemental analysis of the adsorbent composition, FT-IR, XRD, and SEM spectra analysis. Depending on the initial concentration of the solution used, the adsorption efficiency of copper(II) ions was 58-80% for D-I and 80-97% for D-II. The adsorption mechanism in the case of D-II dolomite was mainly based on ion exchange, while chemisorption dominated the D-I dolomite surface. Considering the possibility of the regeneration and reuse of the adsorbent, dolomite D-II is a better material (the desorption efficiency of copper(II) ions was 58-80%). The adsorption behavior of dolomites has been described using six adsorption isotherms. The best fit was obtained for the Redlich-Peterson, Jovanović, and Langmuir isotherms, indicating that monolayer adsorption occurred. The maximum adsorption capacity for copper(II) was 378 mg/g of D-I and 308 mg/g of D-II.


Activating and tuning basal planes of MoO₂, MoS₂, and MoSe₂ for hydrogen evolution reaction.
We investigated the defected two-dimensional materials MoX2 (X = O, S, Se) for hydrogen evolution reaction by first principles calculations. While the basal plane is inert for pristine MoX2, we found that the defected MoX2 can adsorb hydrogen atoms at defect sites, with appropriate adsorption energies for hydrogen evolution. By analyzing density of states and charge density, we showed that a dangling bond state slightly below the Fermi energy emerges when a defect is created. We proposed that this state is responsible for hybridizing with the hydrogen atom 1s state and hence the adsorption. Knowing the mechanism, we further considered tuning the reaction using adatoms (several first-row transition metals, B, C, N, O). We found that C and O adatoms can make defected MoX2 ideal for hydrogen evolution at higher defect levels (H coverage).


Kinetics of membrane internalization and recycling during pinocytosis in Dictyostelium discoideum.
Internalization and recycling of plasma membrane during pinocytosis in Dictyostelium discoideum was analyzed quantitatively. A labeling technique was used by which [3H]galactose could be enzymatically bound to and released from the plasma membrane. Label internalized with the plasma membrane was no longer accessible to enzymatic release and could therefore be distinguished quantitatively from label remaining on the cell surface. Internalization of labeled membrane components was measured as a function of pinocytotic uptake. Direct experimental evidence for membrane recycling was obtained by demonstrating that previously internalized label reappeared at the plasma membrane. The experimental data agree with a kinetic model requiring that a shuttle of membrane between two membrane compartments leads to the same surface concentration of label in both. The two compartments consist of the plasma membrane and of cytoplasmic vacuolar membranes; their relative membrane surface areas are 1 and 0.5, respectively. One surface area equivalent of the plasma membrane is internalized during a pinocytotic uptake amounting to 15% of the cell volume. At the observed rate of pinocytosis, this occurred once every 45 min. The average size of the primary pinosomes, as weighted according to their contribution to pinocytotic uptake, was calculated to be about 0.6 microns.


Safety and Efficacy of Gadoxetate Disodium-Enhanced Liver MRI in Pediatric Patients Aged >2 Months to <18 Years-Results of a Retrospective, Multicenter Study.
To assess the safety and efficacy of gadoxetate disodium-enhanced liver MR imaging in pediatric patients. Retrospective, multicenter study including pediatric patients aged >2 months to <18 years who underwent contrast-enhanced liver MRI due to focal liver lesions. A single intravenous bolus injection of 0.025 to 0.05 mmol/kg body weight of gadoxetate disodium was administered. Adverse events (AEs) up to 24 hours after injection were recorded and a one-year follow-up was conducted for all serious and unexpected AEs. Efficacy was defined based on the additional diagnostic information obtained from the combined (pre- and postcontrast) image sets as compared with the precontrast image sets by blinded reading. A total of 52 patients for safety and 51 patients for efficacy analyses were evaluated. Twenty-two patients (42.3%) reported a total of 51 serious AEs (SAEs) and one AE after one year. No SAE or AE was related to gadoxetate disodium injection. Gadoxetate disodium-related effects on vital signs were not seen. Additional diagnostic information was obtained for 86.3% of patients. The three most improved efficacy variables were lesion-to-background contrast, lesion characterization, and improved border delineation in 78.4%, 76.5%, and 70.6% of patients, respectively. Gadoxetate disodium in pediatric patients did not raise any clinically significant safety concern. Contrast enhancement provided additional clinically relevant information.


Giant room temperature magnetoimpedance in La0.7Ba0.15Sr0.15MnO3 and development of a sensitive position detector.
Observation of room temperature giant magnetoimpedance in La0.7Ba0.15Sr0.15MnO3 compound having nanometric grain size is reported under low magnetic field and over the frequency range between 50 KHz and 15 MHz. Both the resistive and reactive components of impedance increase with increasing frequency due to skin effect of the metallic state below T(C). Above a critical frequency (1 MHz), a sharp increase in both R and X and hence Z is observed. The applied magnetic field influences the impedance by affecting the penetration depth via the transverse permeability and gives rise to large magnetoimpedance (approximately 70%) at low fields up to 0.1 T. Magnetoimpedance of La0.7Ba0.15Sr0.15MnO3 compound display major change (approximatley 61%) between 0.02 and 0.035 T and appears to originate due to the spin alignment of the charge carriers across the grain boundaries. At fields > 0.1 T, magnetoimpedance displays near saturation, corresponding to the completion of the spin alignment across the grain boundaries. An unique scaling behavior has been observed for field dependence of magnetoimpedance at various frequencies, which could be well accounted by a phenomenological model. Feasibility of the development of a sensitive linear position sensor is also demonstrated.


Bias from removing read duplication in ultra-deep sequencing experiments.
Identifying subclonal mutations and their implications requires accurate estimation of mutant allele fractions from possibly duplicated sequencing reads. Removing duplicate reads assumes that polymerase chain reaction amplification from library constructions is the primary source. The alternative-sampling coincidence from DNA fragmentation-has not been systematically investigated. With sufficiently high-sequencing depth, sampling-induced read duplication is non-negligible, and removing duplicate reads can overcorrect read counts, causing systemic biases in variant allele fraction and copy number variation estimations. Minimal overcorrection occurs when duplicate reads are identified accounting for their mate reads, inserts are of a variety of lengths and samples are sequenced in separate batches. We investigate sampling-induced read duplication in deep sequencing data with 500× to 2000× duplicates-removed sequence coverage. We provide a quantitative solution to overcorrection and guidance for effective designs of deep sequencing platforms that facilitate accurate estimation of variant allele fraction and copy number variation. A Python implementation is freely available at https://bitbucket.org/wanding/duprecover/overview CONTACT: : firstname.lastname@example.com, email@example.com Supplementary information: Supplementary data are available at Bioinformatics online.


Divergent evolution and molecular adaptation in the Drosophila odorant-binding protein family: inferences from sequence variation at the OS-E and OS-F genes.
The Drosophila Odorant-Binding Protein (Obp) genes constitute a multigene family with moderate gene number variation across species. The OS-E and OS-F genes are the two phylogenetically closest members of this family in the D. melanogaster genome. In this species, these genes are arranged in the same genomic cluster and likely arose by tandem gene duplication, the major mechanism proposed for the origin of new members in this olfactory-system family. We have analyzed the genomic cluster encompassing OS-E and OS-F genes (Obp83 genomic region) to determine the role of the functional divergence and molecular adaptation on the Obp family size evolution. We compared nucleotide and amino acid variation across 18 Drosophila and 4 mosquito species applying a phylogenetic-based maximum likelihood approach complemented with information of the OBP three-dimensional structure and function. We show that, in spite the OS-E and OS-F genes are currently subject to similar and strong selective constraints, they likely underwent divergent evolution. Positive selection was likely involved in the functional diversification of new copies in the early stages after the gene duplication event; moreover, it might have shaped nucleotide variation of the OS-E gene concomitantly with the loss of functionally related members. Besides, molecular adaptation likely affecting the functional OBP conformational changes was supported by the analysis of the evolution of physicochemical properties of the OS-E protein and the location of the putative positive selected amino acids on the OBP three-dimensional structure. Our results support that positive selection was likely involved in the functional differentiation of new copies of the OBP multigene family in the early stages after their birth by gene duplication; likewise, it might shape variation of some members of the family concomitantly with the loss of functionally related genes. Thus, the stochastic gene gain/loss process coupled with the impact of natural selection would influence the observed OBP family size.


Dose correlation for thoracic motion in radiation therapy of breast cancer.
This work investigates the dose correlation for deformed objects due to thoracic motion for radiotherapy treatment of breast cancer. An analytical model has been developed to reconstruct patient anatomy based on the assumption that the body will expand or compress proportionally during respiration. The patient geometry at any phase during a breathing pattern is reconstructed using the CT data taken at the inspiration and expiration phases and the breathing level which can be related to the measured chest wall motion. A correlation between the voxels in the inspiration (or expiration) geometry and the voxels in the reconstructed geometry at any phase of the breathing pattern is established so that the dose can be accumulated during a treatment. The method has been implemented for treatment planning dose calculation by interfacing with a Monte Carlo code. The patient geometry files for different phases of the breathing pattern are generated and the three-dimensional dose data are obtained from the Monte Carlo simulations. The final dose distribution is reconstructed from the dose data at different breathing phases based on patient's breathing pattern associated with chest wall movements.


Luminol-dependent chemiluminescence is related to the extracellularly released reactive oxygen intermediates in the case of rat neutrophils activated by formyl-methionyl-leucyl-phenylalanine.
Luminol is a non-radical-specific amplifying molecule which produces light upon interaction with various reactive oxygen intermediates (ROIs). ROI production of rat peritoneal polymorphonuclear leukocytes (PMNLs) elicited by 2.3 microM formyl-methionyl-leucyl-phenylalanine (fMLP) results in a biphasic luminol-dependent chemiluminescence (LDCL) signal. Whereas ROIs are also produced intracellularly, as judged by flow cytometry, addition of non-membrane-permeable catalase reduces the first and second phases of the LDCL signal to around 3% and less than 3%, respectively. This suggests that in the case of fMLP-stimulated rat PMNLs, the LDCL signal is related to the ROIs in the extracellular medium and hydrogen peroxide has a key role in the formation of the LDCL signal. In the presence of the non-specific myeloperoxidase inhibitor Na-azide, the first phase of the LDCL signal decreases slightly (87+/-8%), while the second phase almost disappears (< 3%), indicating the myeloperoxidase dependence of the second phase. The hydroxyl radical scavenger histidine results in an 84+/-4% and a 71+/-4% decrease in the intensity of the first and second phases, respectively. Based on these data, it is concluded that hydrogen peroxide might be the source of hydroxyl radicals directly oxidizing luminol in the first phase of the LDCL signal, while in the second phase it serves as a substrate of myeloperoxidase in the peroxidation reaction of the luminol.


Why do surgical packs cause peritoneal adhesions?
Our experiments in the Porton rat have shown that the foreign debris from surgical sponges left in the peritoneal cavity after use is not the cause of peritoneal adhesions. Instead, the abrasive effect of introducing the sponge produces mesothelial trauma. This is the stimulus for an inflammatory response, followed by adherence of adjacent involved peritoneal surfaces. Adhesions formation did not occur between the abraded peritoneal surfaces of mobile intraabdominal viscera, which suggests that intestinal motility in the early postoperative period is important in the prevention of adhesions.


[Operative treatment of paranasal sinus diseases in childhood].
An exact knowledge of the developing anatomy and physiology, and very conservative operative technique are the prerequisites for surgical therapy of the nose and the paranasal sinuses in children. These requirements are fulfilled by uncapping of the ethmoidal cells in chronic and especially acute ethmoid sinusitis. Intranasal antrostomy allows diagnosis to be made and limited local treatment to be given in acute and chronic maxillary sinusitis. More radical surgical procedures are not indicated in children, except in those cases, where severe orbital or endocranial complications have already developed. Uncapping of the ethmoidal cells and/or intranasal antrostomy combined with the elimination of mechanical obstruction of the upper respiratory tract are necessary, when conservative treatment of acute or chronic sinusitis is unsuccessful. Continuation of conservative therapy is then no longer indicated. The uncapping of the ethmoidal cells under antibiotic cover usually leads to a complete disappearance of the symptoms within a few days, even when orbital or periorbital complications of an acute ethmoiditis have already set in. Even after unsuccessful long-term treatment of a chronic maxillary sinusitis, intranasal antrostomy is successful in 75-90 per cent of cases. Complications did not occur in a personal series of 1,349 intranasal antrostomies in children in a period of 5 years.


Coating electrospun poly(epsilon-caprolactone) fibers with gelatin and calcium phosphate and their use as biomimetic scaffolds for bone tissue engineering.
Electrospinning was employed to fabricate fibrous scaffolds of poly(epsilon-caprolactone) in the form of nonwoven mats. The surfaces of the fibers were then coated with gelatin through layer-by-layer self-assembly, followed by functionalization with a uniform coating of bonelike calcium phosphate by mineralization in the 10 times concentrated simulated body fluid for 2 h. Transmission electron microscopy, water contact angle, and scanning electron microscopy measurements confirmed the presence of gelatin and calcium phosphate coating layers, and X-ray diffraction results suggested that the deposited mineral phase was a mixture of dicalcium phosphate dehydrate (a precursor to apatite) and apatite. It was also demonstrated that the incorporation of gelatin promoted nucleation and growth of calcium phosphate. The porous scaffolds could mimic the structure, composition, and biological function of bone extracellular matrix. It was found that the preosteoblastic MC3T3-E1 cells attached, spread, and proliferated well with a flat morphology on the mineralized scaffolds. The proliferation rate of the cells on the mineralized scaffolds was significantly higher (by 1.9-fold) than that on the pristine fibrous scaffolds after culture for 7 days. These results indicated that the hybrid system containing poly(epsilon-caprolactone), gelatin, and calcium phosphate could serve as a new class of biomimetic scaffolds for bone tissue engineering.


[Clinico-pharmacological studies on the course of high-dose methotrexate therapy in childhood. A retrospective comparison of centers].
In a retrospective study with comparison of two centres (Homburg and Munich) the response of 91 cycles of high-dose methotrexate treatment (4.2-13.6 g/m2 body-surface) was assessed in eight children with osteosarcoma and one with chondrosarcoma. Accompanying treatment (alkalization, infusion and leucovorin "rescue") was undertaken to reduce the methotrexate serum level 48 hours after infusion to below 0.4 mumol/l and thus avoid toxic effects. In the course of these treatment cycles there was a fall in urinary pH values below 7.0 in 59% (Homburg) and 75% (Munich) treatment cycles. On average there were lower methotrexate serum levels 24 and 48 hours after methotrexate administration among the Homburg patients than those in Munich. If urinary pH values fell to below 7.0, a decrease in leucocyte count below 2,000/mm3 was observed in 65% and 70%, respectively. The data indicate the need of carefully measuring urinary pH and methotrexate serum concentration during high-dosage methotrexate treatment and thus decrease the danger of bone-marrow damage.


Enabling Stereochemical Communication and Stimuli-Responsive Chiroptical Properties in Biphenyl-Capped Cyclodextrins.
Chiroptical materials are gaining increasing interest due to their innovative character and their applications in optoelectronics and data encryption technologies. Fully harnessing the potential of building blocks from the "chiral pool", such as native cyclodextrins (CDs), as they often lack chromophores suitable for the construction of materials with significant chiroptical properties. Here, we present the synthesis and characterization of a two-level molecular stack consisting of a point-chiral element (CD) and an axially chiral element (biphenyl), capable of effectively translating the overall stereochemical information contained in CDs into stimuli-responsive chiroptical properties. α- and β-permethylated CDs were efficiently capped with two different 2,2'-difunctionalized 1,1'-biphenyl units. In CD derivatives containing the rigid 2,2'-dihydroxy-1,1'-biphenyl cap, two intramolecular hydrogen bonds act synergistically as stereoselective actuators, enabling effective communication between the two levels and the transfer of nonchromophoric stereochemical information from the cyclic-oligosaccharide to the atropoisomeric cap. The chiroptical properties can be finely tuned by external stimuli such as temperature and solvent. The way chirality is transferred from the CD platform to the biphenyl cap was revealed thanks to crystallographic and computational analyses, together with electronic circular dichroism (ECD) studies.


Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer.
In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m⁶A, m⁵C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer.


Recognition of facial expressions is moderated by Islamic cues.
Recognising emotions from faces that are partly covered is more difficult than from fully visible faces. The focus of the present study is on the role of an Islamic versus non-Islamic context, i.e. Islamic versus non-Islamic headdress in perceiving emotions. We report an experiment that investigates whether briefly presented (40 ms) facial expressions of anger, fear, happiness and sadness are perceived differently when covered by a niqāb or turban, compared to a cap and shawl. In addition, we examined whether oxytocin, a neuropeptide regulating affection, bonding and cooperation between ingroup members and fostering outgroup vigilance and derogation, would differentially impact on emotion recognition from wearers of Islamic versus non-Islamic headdresses. The results first of all show that the recognition of happiness was more accurate when the face was covered by a Western compared to Islamic headdress. Second, participants more often incorrectly assigned sadness to a face covered by an Islamic headdress compared to a cap and shawl. Third, when correctly recognising sadness, they did so faster when the face was covered by an Islamic compared to Western headdress. Fourth, oxytocin did not modulate any of these effects. Implications for theorising about the role of group membership on emotion perception are discussed.


Fabrication of a novel bone ash-reinforced gelatin/alginate/hyaluronic acid composite film for controlled drug delivery.
In this study, a novel pH-sensitive composite film with enhanced thermal and mechanical properties was prepared by the incorporation of bone ash at varying concentrations from 0 to 10v.% into gelatin/sodium alginate/hyaluronic acid (Gel/SA/HyA) polymeric structure for colon-specific drug delivery system. Films were characterized by FT-IR, SEM, and XRD analyses. Thermal and mechanical performances of films were determined by DSC, TGA and universal mechanical tester, respectively. Results proved that thermal stability and mechanical properties of bone ash-reinforced composite films improved significantly with respect to that of neat Gel/SA/HyA film. Cytotoxicity assay for composite films was carried out by using L929 cells. Water uptake capacity of films was determined by swelling test. Herein, release experiments of 5-Fluorouracil (5-FU) were performed in two different solutions (pH 2.1 and 7.4). The results assured that Gel/SA/HyA film containing BA could be considered as a potential biomaterial for controlled drug delivery systems.


Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing.
Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors p16Ink4a (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19Arf (an alternative reading frame product of Cdkn2a,), and p27Kip1 (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The p16Ink4a and p19Arf knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27Kip1 knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.


A three-dimensional semi-analytical solution for predicting drug release through the orifice of a spherical device.
Three-dimensional solute transport was investigated for a spherical device with a release hole. The governing equation was derived using the Fick's second law. A mixed Neumann-Dirichlet condition was imposed at the boundary to represent diffusion through a small region on the surface of the device. The cumulative percentage of drug released was calculated in the Laplace domain and represented by the first term of an infinite series of Legendre and modified Bessel functions of the first kind. Application of the Zakian algorithm yielded the time-domain closed-form expression. The first-order solution closely matched a numerical solution generated by Mathematica(®). The proposed method allowed computation of the characteristic time. A larger surface pore resulted in a smaller effective time constant. The agreement between the numerical solution and the semi-analytical method improved noticeably as the size of the orifice increased. It took four time constants for the device to release approximately ninety-eight of its drug content.


Phylogeny of the Mycoplasma mycoides cluster based on analysis of five conserved protein-coding sequences and possible implications for the taxonomy of the group.
A phylogenetic tree of the Mycoplasma mycoides cluster was inferred from a set of concatenated sequences from five housekeeping genes (fusA, glpQ, gyrB, lepA and rpoB). The relevance of this phylogeny was reinforced by detailed analysis of the congruence of the phylogenies derived from each of the five individual gene sequences. Two subclusters were distinguished. The M. mycoides subcluster comprised M. mycoides subsp. mycoides biotypes Small Colony (SC) and Large Colony (LC) and M. mycoides subsp. capri. The latter two groups could not be clearly separated, which supports previous proposals that they be united into a single taxonomic entity. The Mycoplasma capricolum subcluster included M. capricolum subsp. capricolum, M. capricolum subsp. capripneumoniae and Mycoplasma sp. bovine group 7 of Leach, a group of strains that remains unassigned. This group constituted a distinct branch within this cluster, supporting its classification as a subspecies of M. capricolum. Mycoplasma cottewii and Mycoplasma yeatsii clustered in a group that was distinct from Mycoplasma putrefaciens and they were all clearly separated from the M. mycoides cluster. In conclusion, this approach has allowed us to assign phylogenetic positions to all members of the M. mycoides cluster and related species and has proved the need to adjust the existing taxonomy. Furthermore, this method may be used as a reference technique to assign an unequivocal position to any particular strain related to this cluster and may lead to the development of new techniques for rapid species identification.


Computational System Level Approaches for Discerning Reciprocal Regulation of IL10 and IL12 in Leishmaniasis.
IL12 and IL10 are two of the major cytokines which control the fate of Leishmaniasis. This paper presents two models healthy state and diseased state which shows how secretion of IL12 is responsible for parasite elimination and IL10 can jeopardize the parasite elimination and promote its survival. Epigenetic modification in the host IL12 and IL10 promoter can decide the fate of parasites. It was observed that reciprocal relationship exists between IL12 and IL10 and that is majorly controlled by a transcription factor NFAT5 from Rel family of transcription factors. By targeting this transcription factor at the cellular level, it might be possible to modulate the release of powerful pro-inflammatory cytokines, thereby reducing parasite survival. The mathematical models developed here serves as a step towards finding a key component that can pave a way for therapeutic investigation.


Gastrointestinal complications in gynecologic surgery: a review for the general gynecologist.
A working familiarity with the management of common perioperative gastrointestinal complications is required for all general gynecologists. Thermal gastrointestinal injury requires resection of the damaged portion of bowel unless the injury involves only the bowel serosa and is less than 0.5 cm in diameter. Small intraoperative lacerations of the intestine can be closed primarily, whereas larger lacerations often require resection. Some degree of postoperative ileus may be expected, but prolonged ileus requires nasogastric suctioning while excluding bowel obstruction, peritonitis, or electrolyte imbalance. Small-bowel obstruction, most likely to be caused by postoperative adhesions, can often be treated successfully by gastrointestinal intubation. Steps required in the initial management of an enterocutaneous fistula include institution of parenteral nutritional supplementation and antibiotics, skin protection, and investigative studies of the fistula. Preventive measures may be used at the time of any surgical procedure to reduce the incidence of many of these complications.


Effects of 4-week mindfulness training versus adaptive cognitive training on processing speed and working memory in multiple sclerosis.
The aim of this preregistered, secondary analysis of a pilot randomized controlled trial (NCT02717429) was to compare the impact of 4-week mindfulness-based training and adaptive cognitive training, with a waitlist control condition, on processing speed and working memory in people with multiple sclerosis (PwMS). Sixty-one PwMS were randomized to mindfulness-based training (MBT), adaptive computerized cognitive training (aCT), or a waitlist (WL) control group and completed the Brief Repeatable Battery of Neuropsychological Tests at pre- and posttraining. Training-related changes on the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) were the primary outcomes of interest. Baseline cognitive status was examined as a moderator of treatment gains. Practice time, change in aCT game difficulty, and rate of change in state awareness across MBT were assessed as correlates of cognitive gains. Compared with aCT and WL, mindfulness training significantly improved processing speed (ηp² = .14). Baseline cognitive status did not moderate change in processing speed (ηp² = .005) or working memory (ηp² = .014). Practice time and change in game difficulty were not significantly correlated with cognitive gains (all ps > .49). In the MBT group, rate of change in awareness was significantly associated with improvement in working memory (ρ = .52, p = .04). In PwMS, 4 weeks of mindfulness meditation training improved processing speed above and beyond aCT and WL. More rapid change in awareness during mindfulness training may be associated with greater gains in working memory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.
Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.


Co-expression of autophagic markers following photodynamic therapy in SW620 human colon adenocarcinoma cells.
Photodynamic therapy (PDT) is a minimally invasive cancer treatment. It involves the combination of a photosensitizer and light of a specific wavelength to generate singlet oxygen and other reactive oxygen species that lead to tumor cell death. Autophagy is one of the pathways that tumor cells undergo during photodamage and it is common in photodynamic therapy. The aim of this study was to examine the effect of in vitro PDT on the expression of autophagy‑related proteins, autophagy related 7 (Atg7), light chain 3 (LC3) and Beclin‑1. Human SW620 colon carcinoma cells were treated with 5-aminolevulinic acid (ALA)‑based PDT at a dose of 3 mM. The irradiation was performed using 4.5 J/cm2 total light and a fluence rate of 60 mW/cm2. Autophagy was evaluated by immunocytochemistry using specific antibodies to Atg7, Beclin‑1 and LC3. The evaluation was repeated at several time points (0, 4, 8 and 24 h) following irradiation. The induction of autophagy was observed directly following the 5‑ALA‑mediated PDT procedure with the strongest expression of autophagy-related proteins at 4 and 8 h after irradiation as demonstrated using immunocytochemistry. It was characterized by significantly increased expression of Beclin‑1, Atg7 and LC3. To the best of our knowledge this is the first study to analyze Beclin‑1, Atg7 and LC3 expression in a PDT‑related experiment. This study enhances the understanding of the role of autophagy in PDT, which may contribute to better and more effective tumor responses to this therapy.


Evidence of regression of fibropapillomas in juvenile green turtles Chelonia mydas caught in Niterói, southeast Brazil.
Fibropapillomatosis is a disease characterized by cutaneous tumors affecting all marine turtle species, but mostly Chelonia mydas. The disease was first reported in 1938, and since then, the number of sightings has been increasing over the years. This disease can cause many complications in the affected animal and can lead to death, and is thus included in the many threats to marine turtle populations. It is still not known for certain what causes this disease, although many studies indicate a herpesvirus as the main etiologic agent. The incidence of fibropapillomatosis is rarely reported in adults, leading to speculations that there may be a cure for the disease or that the animals die before reaching adulthood. In this paper, 2 cases of fibropapillomatosis regression are reported from juvenile C. mydas caught between July 2008 and July 2010 in the coastal zone of Itaipu, Niterói, Rio de Janeiro, Brazil. These individuals were identified photographically upon recapture. One individual had a total regression (disappearance) of external papilloma within 164 d between first capture and recapture, and the other individual had a partial regression (decrease in size) observed within 13 to 188 d of recapture. The mechanism that triggers the regression is still unknown but is likely to be an immune system response or removal of the tumor promoter. There are few reported cases of regression in the world, and constant monitoring through mark-recapture is necessary to assess whether the marine turtles affected by this disease have real chances of survival.


Pregaming among Latina/o emerging adults: Do acculturation and gender matter?
Among ethnic minority groups, Latina/o emerging adults are most likely to engage in pregaming, a risky drinking practice. This study examined how U.S. acculturation and enculturation are associated with pregaming and the extent to which gender moderates this relation in a sample of 312 Latina/o emerging adults (18 - 25 years of age). Results indicated that men consumed more alcohol when pregaming than women, but there were no gender differences in pregaming frequency. Results also showed that lower levels of U.S. acculturation were associated with greater alcohol consumption while pregaming for men, but not women. Gender did not moderate the association between acculturation and pregaming frequency. This study highlights the need to account for gender when examining sociocultural determinants of high risk drinking behaviors such as pregaming among Latina/o emerging adults.


[Do HLA-B37 and HLA-B27 antigens cross react?].
Anti-HLA-B37 serum of Behringwerke gave a positive cytotoxic test with 18 of 24 samples of B37 negative B27 positive lymphocytes. With lymphocytes which had none of these antigens the reaction was always negative. The author discusses whether the results are evidence of the cross reactivity between antigens HLA-B37 and B27 or whether it is due to traces of anti-HLA-B27 antibodies in the above serum.


[Multidrug-resistant Klebsiella pneumoniae, predisposing factors and associated mortality in a tertiary-care hospital in Colombia].
Bacterial resistance to antibiotics is a serious public health problem that is increasing worldwide. Resistant (R) Klebsiella pneumoniae is one of the main pathogens isolated in nosocomial infections. The aim of this study was to explore risk factors associated with the acquisition of infection by R-K. pneumoniae and mortality. Prospective cohort study conducted in a hospital of high complexity of Medellin, October/2009-April/2010. The exposed group was defined as patients infected with R-K. pneumoniae (producing b-lactamases or carbapenemases). In order to identify risk factors associated with infection by R-K. pneumoniae and 30 day mortality, logistic regression and Cox proportional hazards regression were used. 243 patients were included in the study, 84 infected with R-K. pneumoniae and 159 infected with susceptible K. pneumoniae. Female sex (OR = 2.51 95% 1.37 to 4.6), the co-existence of cardiovascular disease (OR = 2.13 95% CI 1.14 to 3.99), previous use of ceftriaxone (OR = 9.52 95% CI 2.63 to 34.46) and carbapenems (OR = 4.23 95% CI 2.41 to 7.42) were risk factors associated to infection with R-K. pneumoniae. Some predictors of mortality were malignant neoplasia (HR = 4.43 95% CI 2.13 to 9.22) and mechanical ventilation (HR = 3.81 95% CI 1.99 to 7.28). There was no difference in 30-day mortality when comparing patients in both groups. Female gender, cardiovascular disease and previous use of antimicrobials were associated with infection by R-K. pneumoniae. Thirty-day mortality was similar in both groups of patients.


13C and 1H nuclear magnetic resonance study of glycogen futile cycling in strains of the genus Fibrobacter.
We investigated the carbon metabolism of three strains of Fibrobacter succinogenes and one strain of Fibrobacter intestinalis. The four strains produced the same amounts of the metabolites succinate, acetate, and formate in approximately the same ratio (3.7/1/0.3). The four strains similarly stored glycogen during all growth phases, and the glycogen-to-protein ratio was close to 0.6 during the exponential growth phase. 13C nuclear magnetic resonance (NMR) analysis of [1-13C]glucose utilization by resting cells of the four strains revealed a reversal of glycolysis at the triose phosphate level and the same metabolic pathways. Glycogen futile cycling was demonstrated by 13C NMR by following the simultaneous metabolism of labeled [13C]glycogen and exogenous unlabeled glucose. The isotopic dilutions of the CH2 of succinate and the CH3 of acetate when the resting cells were metabolizing [1-13C]glucose and unlabeled glycogen were precisely quantified by using 13C-filtered spin-echo difference 1H NMR spectroscopy. The measured isotopic dilutions were not the same for succinate and acetate; in the case of succinate, the dilutions reflected only the contribution of glycogen futile cycling, while in the case of acetate, another mechanism was also involved. Results obtained in complementary experiments are consistent with reversal of the succinate synthesis pathway. Our results indicated that for all of the strains, from 12 to 16% of the glucose entering the metabolic pathway originated from prestored glycogen. Although genetically diverse, the four Fibrobacter strains studied had very similar carbon metabolism characteristics.


Construction of whole genome radiation hybrid panels and map of chromosome 5A of wheat using asymmetric somatic hybridization.
To explore the feasibility of constructing a whole genome radiation hybrid (WGRH) map in plant species with large genomes, asymmetric somatic hybridization between wheat (Triticum aestivum L.) and Bupleurum scorzonerifolium Willd. was performed. The protoplasts of wheat were irradiated with ultraviolet light (UV) and gamma-ray and rescued by protoplast fusion using B. scorzonerifolium as the recipient. Assessment of SSR markers showed that the radiation hybrids have the average marker retention frequency of 15.5%. Two RH panels (RHPWI and RHPWII) that contained 92 and 184 radiation hybrids, respectively, were developed and used for mapping of 68 SSR markers in chromosome 5A of wheat. A total of 1557 and 2034 breaks were detected in each panel. The RH map of chromosome 5A based on RHPWII was constructed. The distance of the comprehensive map was 2103 cR and the approximate resolution was estimated to be ∼501.6 kb/break. The RH panels evaluated in this study enabled us to order the ESTs in a single deletion bin or in the multiple bins cross the chromosome. These results demonstrated that RH mapping via protoplast fusion is feasible at the whole genome level for mapping purposes in wheat and the potential value of this mapping approach for the plant species with large genomes.


Enhanced microtubule binding and tubulin assembly properties of conformationally constrained paclitaxel derivatives.
Microtubule binding and tubulin assembly promotion by a series of conformationally restricted paclitaxel (PTX) derivatives was investigated. In these derivatives, the C-4 acetate of the taxane is tethered to the C-3' phenyl at ortho and meta positions with different length linkers. The apparent affinity of these derivatives for GMPCPP-stabilized microtubules was assessed by a competition assay, and their influence on microtubule polymerization was evaluated by measuring the critical concentration of GDP-tubulin in the presence of the respective molecule. In general, taxane derivatives with higher apparent affinity for microtubules induced tubulin assembly more efficiently. Among the derivatives, molecules with the shortest tether display the strongest affinity for microtubules. These derivatives exhibited enhanced microtubule stabilization properties and efficiently induced GDP-tubulin assembly into microtubules at low temperature of 12 degrees C and in the absence of Mg2+ ions in 0.1 M PIPES. Based on molecular dynamics simulations, we propose that the enhanced ability to assemble microtubules by these taxane derivatives is linked to their ability to effectively shape the conformation of the M-loop of tubulin for cross-protofilament interaction.


Atmospheric aerosol: does a background level exist?
Measurements of light-scattering made with an integrating nephelometer at Point Barrow, Alaska, and Mount Olympus, Washington, are in agreement in magnitude, and both sets of measurements also are in agreement with other measurements of light-scattering and turbidity made in remote locations. This agreement suggests that a background level of aerosol exists and that the concept of a background is applicable.


[Survival in 46 patients with hepatocarcinoma treated by chemoembolization].
In this paper we report the results we obtained after chemoembolization in 46 patients with HCC in cirrhosis. Chemoembolization is performed by introducing, through an angiographic catheter placed after the origin of the gastroduodenal artery, 20 mg of Doxorubicin Chlorhydrate mixed with 20 ml of Lipiodol and with 10 ml of contrast agent followed by embolization with Spongostan. Chemoembolization results were assessed comparing site, size and local spread of the tumor, hepatic compromission (according to Child's classification) and number of chemoembolization maneuvers with survival in each patient. Overall survival rates are 95.7% at 6 months, 88.5% at 12 months, 60% at 18 months, 36.4% at 24 and 31.8% at 30 months. The best responses were obtained with lesions smaller than 5 cm (100% survival at 6 months, 91.7% at 12 months, 71.4% at 18 and 42.8% at 24 months). Other factors favoring good treatment response were a single lesion (92.9% at 6 months, 91.7% at 12 months, 71.4% at 18 and 42.8% at 24 months), at least 3 cycles of chemoembolization (100% at 6 months, 90% at 12 months, 85.7% at 18 and 42.8% at 24 months) and a low degree of hepatic compromission (Child A and B rather than Child C; in the latter group the survival rates were 75% a 6 months and 0% at 12 months). In conclusion, chemoembolization proves to be the treatment of choice in the HCC patients who cannot undergo surgery.


Radionuclide content and associated radiation hazards of building materials and by-products in Baoji, West China.
Seven types of common building materials and by-products of coal-fired power plants collected from Baoji, West China, were analysed for the natural radioactivity of 226Ra, 232Th and 40K using gamma ray spectrometry with an NaI(Tl) detector. The average activity concentrations vary from 23.0 to 112.2, 20.2 to 147.5 and 113.2 to 890.8 Bq kg(-1) for 226Ra, 232Th and 40K, respectively. The measured activity concentrations for these radionuclides were compared with the data reported from other countries and with the worldwide average activity of soil. As a measure of radiation hazard to the people, the radium equivalent activities, total annual effective dose and activity concentration index were estimated. The radium equivalent activities of the studied samples are below the internationally accepted values. The calculated total annual effective dose and the activity concentration index of seven types of common building materials are <1 mSv y(-1) and 1, respectively. But fly ash and bottom ash exhibit the higher values that exceed and be close to the acceptable values, respectively. This study shows that the measured building materials do not pose any significant source of radiation hazard and are safe for use in the construction of dwellings. Nevertheless, when fly ash and bottom ash are used in dwelling construction, it is important to assess their radiation potential.


[Issues of large scale tissue culture of medicinal plant].
In order to increase the yield and quality of the medicinal plant and enhance the competitive power of industry of medicinal plant in our country, this paper analyzed the status, problem and countermeasure of the tissue culture of medicinal plant on large scale. Although the biotechnology is one of the most efficient and promising means in production of medicinal plant, it still has problems such as stability of the material, safety of the transgenic medicinal plant and optimization of cultured condition. Establishing perfect evaluation system according to the characteristic of the medicinal plant is the key measures to assure the sustainable development of the tissue culture of medicinal plant on large scale.


New knowledge of chlamydiae and the diseases they cause.
The trachoma and LGV organisms, the human pathogens of the species C. trachomatis, cause oculogenital infections and disease syndromes of the eye and genital tract. The incidence of the most prominent disease, endemic trachoma with eye-to-eye transmission, is decreasing all over the world. At the same time there is increasing recognition of high-frequency venereal infections with trachoma organisms and of the genital disease and occasional ocular disease that they cause. Laboratory techniques for diagnosis and investigation are improving, but work with these interesting intermediate agents remains more difficult than that with many other microorganisms. Proper recognition of the diseases is important because specific therapy is available.


The sex difference in dimensional communalities in Macaca nemestrina.
Intr-individual correlations for cranial, mandibular and dental measurements made on lateral skull radiographs of Macaca nemestrina were systematically higher in 30 adult females than in 31 adult males by an average of 0.11 to 0.15, depending upon method of computation. Clearly, for the adult pig-tailed monkey as in Homo during both prenatal and postnatal life, developmental and dimensional communalities are systematically higher in the female indicating a general principle or trend.


Raised plasma adrenomedullin level in Behçet's disease patients.
Abstract To investigate the role of plasma adrenomedullin (AM) in the pathogenesis of Behçet's disease (BD) patients with inactive ocular complications or ocular attack, 18 consecutive BD patients with ocular complications, including 1 BD patient with ocular attack, another group of 6 BD patients with ocular attack, and 10 normal volunteers were evaluated. All BD patients were regularly followed at ophthalmic outpatient clinics. Levels of both total and mature AM in plasma were measured by immunoradiometric assay. Plasma levels of endothelin-1 (ET-1) were also measured by radioimmunoassay. We also measured the levels of C-reactive protein (CRP) in plasma. Levels of total AM in plasma (mean ± SD, 19.6 ± 6.9 fmol/l) were significantly higher in BD patients than in normal volunteers (14.5 ± 3.6 fmol/l) (P = 0.01). The levels of mature AM were also higher in BD patients (1.6 ± 0.4 fmol/l) than in normal volunteers (0.3 ± 0.6 fmol/l) (P = 0.002). The levels of AM in patients with ocular attack were higher than those in normal volunteers, although there was no significant difference compared to levels of AM in BD patients without ocular attack. AM may play an important role as an antiinflammation factor or may reflect endothelial damage as a marker of disease activity in BD patients.


Immobilization of Polymers to Surfaces by Click Reaction for Photocatalysis with Recyclability.
A surface-bound photocatalyst offers advantages of reusability and recyclability with ease. While it can be immobilized by spin coating or drop-casting, a more reliable and durable method involves the formation of a self-assembled monolayer (SAM) on a suitable surface using designer molecules. In this paper, we report devising a practical, durable, and recyclable photocatalytic surface using immobilized polytriazoles of diketopyrrolopyrrole (DPP). While the SAM formation techniques were utilized for superior results, conventional coatings of polymers on surfaces were performed for comparison. Different methods confirmed efficient immobilization and high grafting density for the SAM technique. Computational models suggested favorable energy parameters for active materials. Photocatalytic studies were performed using both immobilized polymers and polymers in solution for comparison. These findings are important for understanding various physicochemical characteristics of polytriazole-functionalized surfaces.


[Spectral Smoothing with Adaptive Multiscale Window Average].
In order to smooth the spectra automatically and reliably, a spectral smoothing algorithm with adaptive multiscale window average (AWMA) is demonstrated. In this method, different positions of the spectra are smoothed by windows of different width, and the width of the windows will directly affect smoothing. The window with inappropriate width may cause excessive denoising (peak distortion or loss) or inadequate denoising (the flat region of the spectra still contains a lot of noise). So, how to get the right width of the window is the key of spectral smoothing. The algorithm optimized the width of windows by an iterative method, and verified whether the width is the best according to statistical Z-test. In order to increase the reliability of the algorithm, a comprehensive comparison of the thresholds of hypothesis according to simulation data of different SNR was performed. When the threshold is set to 1. 1, the denoising effect can be the best. In this work, the AMWA algorithm was tested by simulated spectra and real syectra, and it can automatically adapt to different spectral shape and different noise intensity. A comprehensive comparison of AMWA smoothing, Savitzky-Golay smoothing and moving average smoothing was performed in this paper, and the AMWA algorithm is better than the other two algorithms. Results show that the AMWA algorithm not only has better denoising effect, but also has higher accuracy and fidelity. This method has achieved great effect not only to simulated spectra but also to real spectra.


3D printed membranes of polylactic acid and graphene oxide for guided bone regeneration.
We fabricated graphene oxide (GO)-incorporated polylactic acid (PLA) (GO-PLA) films by using three-dimensional (3D) printing to explore their potential benefits as barrier membranes for guided bone regeneration (GBR). Our results showed that the 3D printed GO-PLA films provided highly favorable matrices for preosteoblasts and accelerated new bone formation in rat calvarial bone defect models.


The Co-development and Feasibility-Testing of an Innovative Digital Animation Intervention (DAISI) to Reduce the Risk of Maternal Sepsis in the Postnatal Period.
Sepsis is one of the most common causes of mortality in postnatal women globally and many other women who develop sepsis are left with severe morbidity. Women's knowledge of postnatal sepsis and how it can be prevented by simple changes to behaviour is lacking. This paper describes the co-development and feasibility testing of a digital animation intervention called DAISI (digital animation in service improvement). This DAISI is designed to enhance postnatal women's awareness of sepsis and how to reduce their risk of developing the condition. We co-designed the digital animation over a six-month period underpinned by theory, best evidence and key stakeholders, translated it into Urdu then assessed its use, firstly in a focus group with women from different Black, Asian and Minority Ethnic (BAME) groups and secondly with 15 clinical midwives and 15 women (including BAME women). Following exposure to the intervention, midwives completed a questionnaire developed from the COM-B behaviour change model and women participated in individual and focus group interviews using similar questions. The animation was considered acceptable, culturally sensitive and simple to implement and follow. DAISI appears to be an innovative solution for use in maternity care to address difficulties with the postnatal hospital discharge process. We could find no evidence of digital animation being used in this context and recommend a study to test it in practice prior to adopting its use more widely. If effective, the DAISI principle could be used in other maternity contexts and other areas of the NHS to communicate health promotion information.


Different effect of alcohol consumption on hypertension according to metabolic health status.
We aimed to investigate whether the effect of problematic alcohol drinking on hypertension differed according to metabolic health statuses. Male participants from the fifth Korea National Health and Nutrition Examination Survey were recruited. Problematic alcohol drinkers were designated as subjects with heavy drinking (⩾30 g per day), binge drinking (⩾7 glasses per day) or a high alcohol use disorders identification test score (⩾20). Metabolically obese status was defined as having ⩾1 or ⩾2 components of the diagnostic criteria for metabolic syndrome, excluding the blood pressure component. Because the prevalence of problematic alcohol drinking and the prevalence of hypertension largely differed by age groups, separate analyses were performed for the two age groups (<50 and ⩾50 years). Among a total of 6329 subjects, 37.04% had hypertension. In the younger age group, subjects with problematic alcohol drinking demonstrated a higher prevalence of hypertension in both nonobese and obese individuals compared with subjects who were nonobese and who were not problematic alcohol drinkers. Of note, problematic alcohol drinking increased the risk of having hypertension ∼3 times in young nonobese individuals who demonstrated a metabolically obese phenotype compared with those who were metabolically healthy. However, metabolic health status did not have a significant impact on the risk for having hypertension in obese participants, regardless of their age groups. For the prevention of hypertension, avoidance of problematic alcohol drinking should be emphasized, especially in young subjects who show poor metabolic health status despite being nonobese.


Multicenter pediatric emergency medicine research and Rhode Island.
Multicenter clinical research studies are often needed to address issues of generalizability, conditions with low incidence, adequate statistical power, and potential study bias. While pediatric research networks began work in the 1950s, and Rhode Island physicians have contributed to many of these studies, pediatric emergency medicine (PEM) collaboratives are relative newcomers. Since the mid-1990s, Rhode Island pediatricians have contributed to multicenter studies of diabetic ketoacidosis, bronchiolitis, asthma, quality of PEM care, meningitis, brief interventions for substance use disorders, point-of-care ultrasound, and pre-hospital triage protocols. In 2011, Rhode Island Hospital joined the Pediatric Emergency Care Applied Research Network, the first federally funded pediatric emergency medicine network of its kind. Its mission is to perform high quality, high impact PEM research. Since joining the network, Rhode Island Hospital has quickly become a productive and valued member of the network, portending a bright future for multicenter PEM research in the Ocean State.


Interaction of recombinant human bone morphogenetic protein-2 with poly(d,l lactide-co-glycolide) microspheres.
The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) with poly(d,l lactide-co-glycolide) (PLGA) porous microspheres provided for "sustained release" of the protein from the microspheres. Soaking 50:50 PLGA microspheres in a buffered rhBMP-2 solution for a sufficient period of time to permit equilibrium binding enabled quantification of "free" and "bound" protein. "Free" protein is defined as protein present within the porous matrix of the microspheres, whereas "bound" refers to protein adsorbed to PLGA surfaces. Kinetics of the rhBMP-2-microsphere association revealed that equilibrium was attained within 8 hr for two buffer systems (arginine/histidine, pH 6.50; and glutamic acid/sodium glutamate, pH 4.50). Increasing the concentration of the rhBMP-2 stock solution used for the interaction studies from 0.025 to 1.0 mg/ml increased the amount of rhBMP-2 adsorbed and the concentration of free rhBMP-2. Beyond a 1.0 mg/mL concentration, only free rhBMP-2 levels increased. Linearized Langmuir treatment of the adsorption data yielded values corresponding to monolayer coverage of the microspheres (Cm) and the equilibrium adsorption constant (K) of 0.17 microgram/cm2 and 7.57 ml/mg, respectively. Studies performed to determine the effect of ionic strength revealed that increasing NaCl and buffer concentration decreased the amount of protein adsorbed. rhBMP-2 release studies, conducted in an isotonic phosphate buffered saline, pH 7.4 vehicle, revealed that free rhBMP-2 was released during an initial period of 72-96 hr. Following this period, there was no discernible release of rhBMP-2 from the microspheres for up to 7 days, suggesting that the bound protein would remain at a defect site and release slowly upon erosion of the polymer. Mass balances performed by using an extraction buffer of high ionic strength confirmed this prediction.


Transgenic probiotica as drug delivery systems: the golden bullet?
Functional human proteins are constitutively produced in genetically modified bacteria that survive on human mucosal surfaces, to the benefit of the host. The successful Phase I clinical trial with IL-10-producing Lactococcus lactis for Crohn's disease has opened new avenues for the use of transgenic bacteria as delivery vehicles. The major advantage of this novel strategy is the avoidance of systemic side effects associated with conventional therapies. This methodology opens up an alternative method for local delivery of therapeutic proteins to various mucosal tissues.


Correlations between Microbiological Outcomes and Clinical Responses in Patients with Severe Pneumonia.
In treatment of pneumonia, microorganisms sometimes persist, appear or reappear despite good clinical responses. On the other hand, recent increasing antibiotic resistance emphases the goal of rapid eradication of pathogen in severe infection. This study was planned to evaluate the correlations between microbiological outcomes and clinical responses in severe pneumonia. Data was gathered from 3 clinical trials regarding severe pneumonia. Microbiological outcomes, determined by serial culture of respiratory tract samples,were compared with clinical outcomes. In total, 146 bacterial strains from 76 patients were analyzed. While clinical success was generally related to total or partial eradication of isolated organisms, Acinetobacter, Enterobacter, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia were often not eradicated and yet were observed in 56% of cases considered clinically successful at the end of antibiotic treatment. Most of the non-eradicated strains (71%) already had or developed resistance against the antibiotics used for treatment. Ten patients relapsed during the follow-up period; 7 of these relapses were associated with 10 non-eradicated organisms. These data raise concern about the pathogenicity of bacteria that persist in the respiratory tract even though good clinical outcomes of pneumonia are achieved, especially when Acinetobacter, Enterobacter, P. aeruginosa, or S. maltophilia were involved. Thus, clinical relapse and development of drug resistance by non-eradicated organisms may be raised.


Mouse dystrophin enhancer preferentially targets lacZ expression in skeletal and cardiac muscle.
Duchenne muscular dystrophy is a muscle wasting disease that results from a dystrophin deficiency in skeletal and cardiac muscle. Studies concerning the regulatory elements that govern dystrophin gene expression in skeletal and/or cardiac muscle in both mouse and human have identified a promoter and an enhancer located in intron 1. In transgenic mice, the muscle promoter alone targets the expression of a lacZ reporter gene only to the right ventricle of the heart, suggesting the need for other regulatory elements to target skeletal muscle and the rest of the heart. Here we report that the mouse dystrophin enhancer from intron 1 can target the expression of a lacZ reporter gene in skeletal muscle as well as in other heart compartments of transgenic mice. Our results also suggest that sequences surrounding the mouse dystrophin enhancer may affect its function throughout mouse development.


Lucky morning glory, Calystegia felix (Convolvulaceae): a new species from Southern California, with notes on the historical ecology of the Chino ciénega belt.
A new morning glory, Calystegia felixProvance & A.C. Sanders sp. nov. (Convolvulaceae), is described from the Los Angeles, San Gabriel, and Santa Ana River basins. Historical collections of the species, which prior to 2011 had not been seen alive in 94 years, have been misidentified as Calystegia sepium (L.) R. Br. subsp. binghamiae (Greene) Brummitt. The undescribed species was rediscovered in the City of Chino in April of 2011, a few miles north of the location where the most recent previous collection had been made by I. M. Johnston in 1917. The plants were found just prior to their likely destruction by grading and trenching for an underground power line. Intensive searches have resulted in the discovery of five additional occurrences, all of them in the City of Chino. Calystegia felix is at high risk of soon becoming extinct in the wild. All of the known extant occurrences are associated with well-watered landscaping on recently completed industrial, commercial, and residential developments. Every known living occurrence is within the limits of a ciénega belt, which is now mostly historical. Otherwise, the new species is only known only from collections made around the turn of the 20(th) century in what are now heavily urbanized areas, including one from South Los Angeles and another from Pico Rivera in Los Angeles County. Calystegia felix lacks the large bracts that immediately subtend, and enclose the calyx, which are always present in members of the Calystegia sepium complex. Affinities to Calystegia felix are found among other western US species with graduated sepals and small, often somewhat remote bracts. We discuss the enduring confusion between Calystegia felix and Calystegia sepium subsp. binghamiae, and differentiate the new species from some of its more likely relatives. The taxonomic treatment is supplemented by photos of herbarium specimens and living plants. We also discuss the ecological setting of Chino's ciénega belt, which was a mosaic of palustrine wetlands.


Correlation of Age, Sex, and Location With Recurrence of Oral Giant Pyogenic Granuloma After Surgical Excision.
This study was carried out to correlate age and sex of the patient as well as location of the oral giant pyogenic granuloma (PG) with the recurrence rate after surgical excision. Seventy-two patients having oral giant PGs were treated by a conservative surgical excision. Information on sex, age, lesion site, and recurrence was collected. Data were reviewed and analyzed to correlate the recurrence rate with sex and age of the patient as well as the location of the lesion. Recurrence of the oral giant PG was occurred in 22.2% of patients. The highest rates of recurrence were observed in the third (33.3%) and fourth (19%) decades of life. The recurrence rate was more common in females (24%) than males (18.2%) and it was predominant in mandibular lesions (25%) than maxillary one (8.3%). On the basis of their results the authors concluded that recurrence of oral giant PG has an obvious correlation with age and sex of the patient as well as location of the lesion.


Rates of entry and oxidation of acetate, glucose, D(-)-beta-hydroxybutyrate, palmitate, oleate and stearate, and rates of production and oxidation of propionate and butyrate in fed and starved sheep.
1. Rates of entry and oxidation of a range of metabolites have been measured in tracheostomized sheep (diet, 800g. of lucerne chaff and 100g. of maize/day) by combining isotope-dilution techniques with the continuous measurement of total respiratory gas exchange, and (14)CO(2) production during the intravenous or intraruminal infusion of (14)C-labelled substrates. 2. Mean entry rates in fed and starved (24hr.) sheep respectively, expressed as mg./min./kg. body wt.(0.75), were: glucose, 5.0 (range 4.8-5.1, 2 observations) and 3.8 (3.2-4.2, 4); acetate, 10.8 (9.1-13.5, 4) and 5.8 (1); d(-)-beta-hydroxybutyrate, 1.4 (1) and 1.5 (0.8-2.4, 4); palmitate, oleate and stearate (starved sheep only) 1.0 (0.6-1.9, 7), 0.9 (0.2-1.6, 10) and 0.9 (0.5-1.1, 11) respectively. 3. Production rates of propionate and butyrate in continuously feeding sheep were 6.4 (4.7-8.3, 4) and 4.3 (3.4-6.1, 4) mg./min./kg.(0.75) respectively, and in starved (24hr.) sheep were 2.5 (2.2-2.9, 2) and 1.0 (0.8-1.2, 2) mg./min./kg.(0.75) respectively. 4. Calculated terminal values for the specific radioactivity of respiratory (14)CO(2) during measurements of entry rates and production rates were used to calculate the contributions of individual substrates to overall oxidative metabolism. Mean values for fed and starved sheep respectively were: glucose, 9.1 (8.6-9.6, 2) and 11.2 (5.9-15.1, 4)%; acetate, 31.6 (26.8-38.1, 4) and 22.1 (1)%; d(-)-beta-hydroxybutyrate, 10.4 (1) and 4.8 (1.9-7.7, 4)%; propionate, 23.0 (13.8-29.9, 4) and 7.1 (6.8-7.4, 2)%; butyrate, 16.5 (13.7-20.5, 4) and 5.3 (5.2-5.3, 2)%; palmitate, oleate and stearate (starved sheep only), 4.7 (2.0-7.7, 7), 4.0 (1.2-6.6, 10) and 4.4 (3.8-5.8, 9)% respectively. The sum of these values for individual substrates in fed and starved sheep, excluding that of beta-hydroxybutyrate and after correction of the glucose value for the known interrelations of this substrate with propionate, accounted for 76% and 58% respectively of total production of carbon dioxide. 5. Calculations based on the proportion of substrate entry directly oxidized indicated that the substrates studied accounted for 63% (fed sheep) and 43% (starved sheep) of total energy expenditure measured by oxygen uptake. The contribution of beta-hydroxybutyrate was excluded, and corrections were made for glucose-propionate interrelations, and for the different rates of oxidation of the methyl and carboxyl fragments of acetate. 6. The present results have been combined with those obtained earlier in this Laboratory to examine the relationships between rates of substrate entry and oxidation, and concentrations of substrate in blood. Rates of entry of acetate, glucose, d(-)-beta-hydroxybutyrate, palmitate and oleate (but not stearate) were well correlated with concentration in blood, and substrate contribution to production of carbon dioxide showed a similar correlation to blood concentration, except with glucose. 7. It was concluded that the general technique is of potential value in providing valid quantitative parameters of animal metabolism.


Biofunctionalization of 3D printed collagen with bevacizumab-loaded microparticles targeting pathological angiogenesis.
Pathological angiogenesis is a crucial attribute of several chronic diseases such as cancer, age-related macular degeneration, and osteoarthritis (OA). In the case of OA, pathological angiogenesis mediated by the vascular endothelial growth factor (VEGF), among other factors, contributes to cartilage degeneration and to implants rejection. In line with this, the use of the anti-VEGF bevacizumab (BVZ) has been shown to prevent OA progression and support cartilage regeneration. The aim of this work was to functionalize a medical grade collagen with poly (lactic-co-glycolic acid) (PLGA) microparticles containing BVZ via three-dimensional (3D) printing to target pathological angiogenesis. First, the effect of several formulation parameters on the encapsulation and release of BVZ from PLGA microparticles was studied. Then, the anti-angiogenic activity of released BVZ was tested in a 3D cell model. The 3D printability of the microparticle-loaded collagen ink was tested by evaluating the shape fidelity of 3D printed structures. Results showed that the release and the encapsulation efficiency of BVZ could be tuned as a function of several formulation parameters. In addition, the released BVZ was observed to reduce vascularization by human umbilical vein endothelial cells. Finally, the collagen ink with embedded BVZ microparticles was successfully printed, leading to shape-stable meniscus-, nose- and auricle-like structures. Taken altogether, we defined the conditions for the successful combination of BVZ-loaded microparticles with the 3D printing of a medical grade collagen to target pathological angiogenesis.


Autotransfusion and hemoseparation in cardiac surgery. What can be saved in cardiac reoperations and operations of thoracic aortic aneurysms?
In 149 patients, scheduled for cardiac reoperations, repair of cyanotic heart disease or resection of aneurysms of the ascending or descending aorta, the effect of intraoperative hemoseparation was studied. The amount of autologous blood which was collected before, during, and after systemic heparinisation and processed to washed packed red cells was registered. Mean packed cell quantities gained intraoperatively were: 1275 (1006-2067) ml (descending aortic aneurysm), 1800 (1186-2500) ml (ascending aortic aneurysm), 1524 (1030-1801) ml (single valve rereplacement), 1896 (1398-2368) ml (double valve rereplacement), 946 (800-1050) ml (coronary artery reoperation), 1362 (922-1455) ml (cyanotic heart disease) and 1519 (1194-2066) ml (miscellaneous cardiac operations). In 35 patients more than 2000 ml and in 14 patients more than 3000 ml packed cells were harvested. Based on body weight, relatively more packed cells could be gained in patients with cyanotic heart disease (41 ml/kg) than in the other groups (21 ml/kg). In these young patients the application of a smaller centrifuge bowl (125 ml) can be helpful. These results demonstrate that cell saving by means of a cell separator with a special suction line and collecting system can help to reduce the donor blood requirement in cardiac operations, in which large intraoperative blood loss is anticipated.


Structural basis of outer dynein arm intraflagellar transport by the transport adaptor protein ODA16 and the intraflagellar transport protein IFT46.
Motile cilia are found on unicellular organisms such as the green alga Chlamydomonas reinhardtii, on sperm cells, and on cells that line the trachea and fallopian tubes in mammals. The motility of cilia relies on a number of large protein complexes including the force-generating outer dynein arms (ODAs). The transport of ODAs into cilia has been previously shown to require the transport adaptor ODA16, as well as the intraflagellar transport (IFT) protein IFT46, but the molecular mechanism by which ODAs are recognized and transported into motile cilia is still unclear. Here, we determined the high-resolution crystal structure of C. reinhardtii ODA16 (CrODA16) and mapped the binding to IFT46 and ODAs. The CrODA16 structure revealed a small 80-residue N-terminal domain and a C-terminal 8-bladed β-propeller domain that are both required for the association with the N-terminal 147 residues of IFT46. The dissociation constant of the IFT46-ODA16 complex was 200 nm, demonstrating that CrODA16 associates with the IFT complex with an affinity comparable with that of the individual IFT subunits. Furthermore, we show, using ODAs extracted from the axonemes of C. reinhardtii, that the C-terminal β-propeller but not the N-terminal domain of CrODA16 is required for the interaction with ODAs. These data allowed us to present an architectural model for ODA16-mediated IFT of ODAs.


Red cell autoantibodies among thalassaemia patients in Hospital Universiti Sains Malaysia.
Thalassaemia is one of the major public health problems in Malaysia. Regular monthly blood transfusion remains the main treatment for severe thalassaemia patients. One of the complications of blood transfusion is the formation by the recipients of alloantibodies and autoantibodies against red blood cell (RBC) antigen. The purpose of this study was to determine the prevalence of RBC autoantibodies among multiple-transfused thalassaemic patients in our institution and factors that contribute to its development. A prospective study was conducted in Haematology Laboratory, Hospital Universiti Sains Malaysia between January 2004 and December 2004. A total of 63 thalassaemia patients, who received regular blood transfusion were included in this study. Clinical and serological data were collected and analysed prospectively. Blood samples were subjected to standard blood bank procedures for screening of antibodies and their subsequent identification using reagent of Diamed-ID Gel microtyping system. There were 49 (77.8 percent) patients with Hb E/beta-thalassaemia, ten (15.9 percent) beta-thalassaemia major, three (4.7 percent) Hb H Constant Spring and one (1.6 percent) Hb H disease. Only one (1.6 percent) patient had autoantibodies. There were no statistical associations found between the formation of autoantibodies with age at the start of transfusion, number of packed cell transfused and splenectomy. Our data showed a low autoimmunisation rate in multiple-transfused thalassaemia patients in our hospital.


Epithelial stratification shapes infection dynamics.
Infections of stratified epithelia contribute to a large group of common diseases, such as dermatological conditions and sexually transmitted diseases. To investigate how epithelial structure affects infection dynamics, we develop a general ecology-inspired model for stratified epithelia. Our model allows us to simulate infections, explore new hypotheses and estimate parameters that are difficult to measure with tissue cell cultures. We focus on two contrasting pathogens: Chlamydia trachomatis and Human papillomaviruses (HPV). Using cervicovaginal parameter estimates, we find that key infection symptoms can be explained by differential interactions with the layers, while clearance and pathogen burden appear to be bottom-up processes. Cell protective responses to infections (e.g. mucus trapping) generally lowered pathogen load but there were specific effects based on infection strategies. Our modeling approach opens new perspectives for 3D tissue culture experimental systems of infections and, more generally, for developing and testing hypotheses related to infections of stratified epithelia.


Oral administration of geranylgeranylacetone plus local somatothermal stimulation: a simple, effective, safe and operable preconditioning combination for conferring tolerance against ischemia-reperfusion injury in rat livers.
To explore a simple, effective, safe and operable pretreatment for conferring tolerance against ischemia-reperfusion (I-R) injury in rat livers. Forty-five rats were divided into five groups (each group n = 9). Group C: control group; group G: geranylgeranylacetone (GGA) was administered without heat stress; group S: local heat stress alone; group WG: GGA plus whole-body heat stress; group SG: GGA administration plus local heat stress. After completion of the I-R procedure, the ischemic-reperfused liver lobes in five groups were resected and tested for heat shock protein (HSP70) by RT-PCR, Western blotting analysis and immunohistochemical staining. The blood samples were collected for ALT and AST measurement at the end of occlusion of blood supply, 30 min after reperfusion, 24, 48, 72 h after surgery from the inferior vena cava. Survival was monitored for 1 wk. The production of HSP70 after I-R injury increased, the liver enzyme levels after reperfusion decreased rapidly, and the survival rates increased in groups C-SG. The combination of GGA plus local somatothermal stimulation is a simple, effective, safe and operable pretreatment to induce HSP70 in patients with liver tumor and cirrhosis before hepatectomy and in donors before harvesting graft for liver transplantation.


Suitability of peracetic acid for sterilization of media for mycoplasma cultures.
The utility of peracetic acid for sterilization of serum and yeast extract additions to mycoplasma medium was studied by culturing six Mycoplasma species. Culture media containing additions that had been sterilized with peracetic acid proved to be as good as filtered components. The use of 0.05 to 0.1% peracetic acid is recommended to sterilize the serum and yeast extract additions since savings in time and equipment can be accomplished.


Cost-effectiveness of Triple Therapy with Telaprevir for Chronic Hepatitis C Virus Patients in Germany.
Background: About 400,000-500,000 people are infected with hepatitis C in Germany. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of first generation protease inhibitors has significantly improved the treatment of hepatitis C genotype 1 patients. The aim of the study was to assess the cost-effectiveness of triple therapy with telaprevir in Germany. Methods: We used a Markov model on disease progression and natural history to assess the cost-effectiveness of triple therapy with telaprevir compared to standard treatment with pegylated interferon and ribavirin. Model structure and inputs were discussed with clinical experts. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of results. Results: The base-case analyses shows that triple therapy results in higher costs (untreated patients: €48,446 vs. €30,691; previously treated patients: €63,228 vs. €48,603) and better outcomes (untreated patients: 16.85 qualily of life years [QALYs] vs. 15.97 QALYs; previously treated patients: 14.16 QALYs vs. 12.89 QALYs). The incremental cost-effectiveness ratio (ICER) was €20,131 per QALY and €30,567 per life year gained (LYG) for previously untreated patients. ICER in treatment experienced patients was €7,664 per QALY for relapse patients, €12,506 per QALY for partial responders and €28,429 per QALY for null responders. Results were robust in sensitivity analyses. Conclusion: Although triple therapy with telaprevir leads to additional costs, there is a high probability of being cost-effective for different thresholds. This health economic analysis makes an important contribution to current debates on cost savings and efficient resource allocation in the German healthcare sector.


Isotypic surface glycoproteins of trypanosomes.
We have identified cloned populations of trypanosomes, derived from different original field isolates and species, which appeared to possess similar variable surface-antigen types when assayed by immune lysis and immunofluorescence tests. Variable surface glycoproteins (VSGs) were isolated from these 'isotypic' trypanosomes. Isolated VSGs had identical apparent mol. wt of 60,000 but different isoelectric points. Radioimmunoassay, using 125I-labelled VSGs and rabbit anti-VSG sera, showed that isotypic VSGs contained not only the cross-reacting determinants found in all other VSGs (Barbet & McGuire, 1978) but also other cross-reacting determinants shared between isotypes. Peptide mapping revealed extensive amino-acid sequence homology between isotype VSGs.


The agouti-related peptide binds heparan sulfate through segments critical for its orexigenic effects.
Syndecans potently modulate agouti-related peptide (AgRP) signaling in the central melanocortin system. Through heparan sulfate moieties, syndecans are thought to anchor AgRP near its receptor, enhancing its orexigenic effects. Original work proposed that the N-terminal domain of AgRP facilitates this interaction. However, this is not compatible with evidence that this domain is posttranslationally cleaved. Addressing this long-standing incongruity, we used calorimetry and magnetic resonance to probe interactions of AgRP peptides with glycosaminoglycans, including heparan sulfate. We show that mature, cleaved, C-terminal AgRP, not the N-terminal domain, binds heparan sulfate. NMR shows that the binding site consists of regions distinct from the melanocortin receptor-binding site. Using a library of designed AgRP variants, we find that the strength of the syndecan interaction perfectly tracks orexigenic action. Our data provide compelling evidence that AgRP is a heparan sulfate-binding protein and localizes critical regions in the AgRP structure required for this interaction.


The High-Performing Radiology Residency: A Case Study.
The primary goal of any radiology residency program is to train clinically competent radiologists. However, some radiology programs go above and beyond basic ACGME requirements and produce highly productive radiologists who contribute to the field in research, education and technology. At the core of such residencies are the people who comprise it, including self-motivated, personable residents and faculty who can facilitate excellence from their trainees. Indeed, radiology residencies which create unique programs in response to evolving resident interests can help foster resident-driven research, advocacy, technological innovation and early leadership. These unique programs, when interwoven with a strong educational foundation driven by evidence-based learning techniques and informatics-driven evaluation programs, function to produce highly competent clinicians who become leaders in the field.


Human urine 1H NMR metabolomics reveals alterations of protein and carbohydrate metabolism when comparing habitual Average Danish diet vs. healthy New Nordic diet.
The aim of this study was to investigate the alteration of the human urine metabolome by means of diet and to compare the metabolic effects of the nutritionally healthy New Nordic Diet (NND) with an Average Danish Diet (ADD). The NND was designed a decade ago by scientists and chefs, based on local and sustainable foods, including fish, shellfish, vegetables, roots, fruit, and berries. The NND has been proven to lower blood pressure, reduce glycemia, and lead to weight loss. The human urine metabolome was measured by untargeted proton nuclear magnetic resonance spectroscopy in samples from 142 centrally obese Danes (20-66 years old), randomized to consume the ADD or the NND. The resulting metabolomics data was processed and analyzed using advanced multivariate data analysis methods to reveal effects related to the design factors, including diet, season, sex, and changes in body weight. Exploration of the nuclear magnetic resonance profiles revealed unique metabolite markers reflecting changes in protein and carbohydrate metabolism between the two diets. Glycine betaine, glucose, trimethylamine N-oxide and creatinine were increased in urine of the individuals following the NND compared with the ADD population, whereas relative concentrations of tartrate, dimethyl sulfone, and propylene glycol were decreased. Propylene glycol had a strong association with the homeostatic model assessment for insulin resistance in the NND group. The food intake biomarkers found in this study confirm the importance of these as tools for nutritional research. Findings from this study provided new insights into the effects of a healthy diet on glycemia, reduction of inflammation, and weight loss among obese individuals, and alteration of the gut microbiota metabolism.


Atmospheric water uptake by an atacama desert shrub.
Nolana mollis, a succulent-leaved shrub of the extreme coastal desert of Chile, has the capacity to condense water on its leaves out of unsaturated atmospheres, Metabolic energy would have to be expended to move this water either from the leaf surface directly to the mesophyll or, when dripped to the soil, from there into the roots. Because of the unusual aridity of its habitat and of the utilization of water-use-efficient metabolism by Nolana, at least during certain periods, such an energy expenditure could be effective.