Characterization of the Arabidopsis nitrate transporter NRT1.6 reveals a role of nitrate in early embryo development.
This study of the Arabidopsis thaliana nitrate transporter NRT1.6 indicated that nitrate is important for early embryo development. Functional analysis of cDNA-injected Xenopus laevis oocytes showed that NRT1.6 is a low-affinity nitrate transporter and does not transport dipeptides. RT-PCR, in situ hybridization, and beta-glucuronidase reporter gene analysis showed that expression of NRT1.6 is only detectable in reproductive tissue (the vascular tissue of the silique and funiculus) and that expression increases immediately after pollination, suggesting that NRT1.6 is involved in delivering nitrate from maternal tissue to the developing embryo. In nrt1.6 mutants, the amount of nitrate accumulated in mature seeds was reduced and the seed abortion rate increased. In the mutants, abnormalities (i.e., excessive cell division and loss of turgidity), were found mainly in the suspensor cells at the one- or two-cell stages of embryo development. The phenotype of the nrt1.6 mutants revealed a novel role of nitrate in early embryo development. Interestingly, the seed abortion rate of the mutant was reduced when grown under N-deficient conditions, suggesting that nitrate requirements in early embryo development can be modulated in response to external nitrogen changes.


Recent irregularities in Table II of Morbidity and Mortality Weekly Report.
Table II of Morbidity and Mortality Weekly Report each week displays the cumulative year-to-date provisional number of cases of selected notifiable diseases in the United States, by state. Thus comparisons between the same weeks for different years can allow a rough rapid tracking of trends. In recent years, particularly 2004, the reported provisional cases showed incongruities. As of April 16, 2004, for example, no AIDS cases at all appeared in Table II. Responses from government public health officials (Centers for Disease Control and Prevention (CDC) and State of California) indicate instabilities and problems in the public health surveillance and reporting system. Such instabilities and problems, if serious and enduring enough, could impair detection of threats to public health.


Feasibility of percutaneous mitral commissurotomy in patients with commissural mitral valve calcification.
Whether a percutaneous mitral commissurotomy (PMC) should be attempted in patients with mitral stenosis (MS) and valvular calcification, especially located at the commissural level remained debated. We sought to evaluate the impact of the degree and location of mitral valve calcifications on PMC results. Over a 3-year period, we enrolled 464 consecutive patients who underwent a PMC at our institution. According to the location (within the body valve leaflets' or at the commissural level) and the degree of calcification, patients were divided into three groups: 261 patients were in Group 1 (no leaflets' or commissural calcification), 141 in Group 2 (leaflets' calcification with no significant commissural calcification), and 62 in Group 3 (at least one commissure significantly calcified). Final valve area (1.83 ± 0.26, 1.71 ± 0.25, and 1.60 ± 0.24 cm(2), P < 0.00001) and the rate of complete opening of at least one commissure (92, 94, and 84%, P = 0.05) were significantly different. However, the rate of post-PMC mitral regurgitation (MR) of grade ≥ 3 (10, 10, and 8%, P = 0.90) was not different among the groups and if the rate of good immediate result, defined as valve area ≥ 1.5 cm(2) with no MR >2/4 was different among the three groups (88, 78, and 73%, P = 0.004), an overallprocedural success could be achieved in most patients with calcified commissures. In this large contemporary series of patients with MS, a procedural success was obtained less frequently in patients with calcified commissure but a successful PMC could still be safely achieved in a large proportion of patients. Our results support the use of PMC as a first-line treatment of patients with severe MS even in the presence of significant commissural calcifications with otherwise favourable clinical characteristics.


An evanescent wave biosensor--Part I: Fluorescent signal acquisition from step-etched fiber optic probes.
A fiber-optic biosensor capable of remote continuous monitoring has recently been designed. To permit sensing at locations separate from the optoelectronic instrumentation, long optical fibers are utilized. An evanescent wave immuno-probe is prepared by removing the cladding near the distal end of the fiber and covalently attaching antibodies to the core. Probes with a radius unaltered from that of the original core inefficiently returned the signal produced upon binding the fluorescent-labelled antigen. To elucidate the limiting factors in signal acquisition, a series of fibers with increasingly reduced probe core radius was examined. The results were consistent with the V-number mismatch, the difference in mode carrying capacity between the clad and unclad fiber, being a critical factor in limiting signal coupling from the fiber probe. However, it was also delineated that conditions which conserve excitation power, such that power in the evanescent wave is optimized, must also be met to obtain a maximal signal. The threshold sensitivity for the optimal step-etched fiber probe was improved by over 20-fold in an immunoassay, although, it was demonstrated that signal acquisition decreased along the probe length, suggesting that a sensor region of uniform radius is not ideal.


CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion.
Active suppression by CD4(+)CD25(+) regulatory T lymphocytes plays an important role in the downregulation of T-cell responses to foreign and self-antigens. To analyze whether the CD4(+)CD25(+) regulatory T lymphocytes exist and function normally in malignant pleural effusion. The percentages of CD4(+)CD25(+) T lymphocytes in pleural effusion and peripheral blood from patients with lung cancer with malignant effusion, pleural lavage and peripheral blood from patients with lung cancer without effusion, and peripheral blood from healthy control subjects were determined by flow cytometry. The expressions of forkhead transcription factor Foxp3 and cytotoxic lymphocyte-associated antigen-4 were also examined. CD4(+)CD25(+) and CD4(+)CD25(-) T cells from pleural effusion and peripheral blood were isolated, and were cultured to observe the effects of CD4(+)CD25(+) cells on proliferation response of CD4(+)CD25(-) T cells in vitro. There were increased numbers of CD4(+)CD25(+) T cells in malignant pleural effusion from patients with lung cancer compared with pleural lavage from patients with lung cancer without pleural effusion, and that these cells have constitutive high-level expression of Foxp3 and cytotoxic lymphocyte-associated antigen-4. Furthermore, CD4(+)CD25(+) T cells mediate potent inhibition of proliferation response of CD4(+)CD25(-) T cells, and anticytotoxic lymphocyte-associated antigen-4 monoclonal antibody could reduce the inhibitory activity of CD4(+)CD25(+) T cells. The increased CD4(+)CD25(+) T cells found in malignant pleural effusion express high levels of Foxp3 transcription factor and potently suppress the proliferation of CD4(+)CD25(-) T cells, and cytotoxic lymphocyte-associated antigen-4 is involved in the suppressive activity of pleural CD4(+)CD25(+) T cells.


Chemical tuning of positive and negative magnetoresistances, and superconductivity in 1222-type ruthenocuprates.
A remarkable variety of conducting states has been found in RuSr2(R2-xCex)Cu2O10-delta ruthenocuprates by tuning the properties of the magnetic CuO2 and RuO2 layers through small changes in the chemistry of the (R,Ce)2O2-delta slab. Both the R3+ cation size and the charge transfer determined by the R/Ce ratio and the oxygen deficiency delta are important controlling parameters that tune ground-state properties from positive magnetoresistive to negative magnetoresistive to superconducting.


Vaccines Meet Big Data: State-of-the-Art and Future Prospects. From the Classical 3Is ("Isolate-Inactivate-Inject") Vaccinology 1.0 to Vaccinology 3.0, Vaccinomics, and Beyond: A Historical Overview.
Vaccines are public health interventions aimed at preventing infections-related mortality, morbidity, and disability. While vaccines have been successfully designed for those infectious diseases preventable by preexisting neutralizing specific antibodies, for other communicable diseases, additional immunological mechanisms should be elicited to achieve a full protection. "New vaccines" are particularly urgent in the nowadays society, in which economic growth, globalization, and immigration are leading to the emergence/reemergence of old and new infectious agents at the animal-human interface. Conventional vaccinology (the so-called "vaccinology 1.0") was officially born in 1796 thanks to the contribution of Edward Jenner. Entering the twenty-first century, vaccinology has shifted from a classical discipline in which serendipity and the Pasteurian principle of the three Is (isolate, inactivate, and inject) played a major role to a science, characterized by a rational design and plan ("vaccinology 3.0"). This shift has been possible thanks to Big Data, characterized by different dimensions, such as high volume, velocity, and variety of data. Big Data sources include new cutting-edge, high-throughput technologies, electronic registries, social media, and social networks, among others. The current mini-review aims at exploring the potential roles as well as pitfalls and challenges of Big Data in shaping the future vaccinology, moving toward a tailored and personalized vaccine design and administration.


Anal Cancer and Anal Intraepithelial Neoplasia Risk among Patients Treated for HPV-Related Gynecological Diseases-A Systematic Review.
The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after the treatment of HPV-related gynecological diseases may have an increased risk of developing a second HPV-related neoplasm anal cancer. The aim of this study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after the treatment of HPV-related gynecological diseases. We conducted a comprehensive review of the available literature from multiple databases. The study was performed following Cochrane Reviewers' Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2. Twenty-five studies were included in the final analysis. Patients after the treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio (SIR) = 5.387, mean incidence risk (IR) = 0.096%, mean IR per 100,000 person-years = 10.37) and AIN (mean IR = 23.683%) compared to the population risk. patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.


Age, body weight and body composition requirements for the onset of sexual maturity of dwarf and normal chickens.
Comparisons of age, food intake, body weight and body composition at the onset of sexual maturity were made between dwarf and normal chickens from lines selected for high or low juvenile body weight. At the same age birds which had started to lay were significantly heavier and contained significantly more abdominal and carcass fat than those which were not laying. Differences between normal and dwarf pullets within lines varied with genetic background, indicating differences between lines in meeting a body weight or a body composition requirement, or both, for the onset of sexual maturity.


Genetic aspects of tumour metastasis.
The application of techniques for the transfer of genetic material between cells when used with recombinant DNA technologies and gene cloning procedures hold exciting possibilities for the genetic analysis of the metastatic behaviour of tumour cells. So far these genetic studies have produced confusing results, but some of the problems have been defined more clearly. For a more complete understanding of the metastatic phenotype a more critical analysis of the models used to mimic the process and a greater appreciation of the deficiencies in the techniques applied to study it are necessary.


Osteochondral avulsion fracture of the femoral origin of the anterior cruciate ligament in an 11-year-old child.
Although tibial end avulsions of the anterior cruciate ligament are relatively common in clinical practice, avulsions of the femoral end of this ligament are by comparison rare. We present the case of an 11-year-old boy with a bony avulsion injury, which was presumed to have arisen from the tibial insertion of the anterior cruciate ligament but turned out instead to be an osteochondral avulsion fracture of the femoral origin. This unexpected finding that was not detected during preoperative workup resulted in the first attempt at surgical fixation being aborted. The need for a second planned definitive fixation procedure emphasises the importance of combining a thorough history and examination in association with appropriate imaging in the patient workup. The patient's definitive operative treatment and outcome are described. Although rare, surgeons (and emergency room doctors) treating such patients should include femoral end avulsion injuries of the anterior cruciate ligament in the differential diagnosis of a child presenting with an acute haemarthrosis of the knee. Furthermore, once diagnosed, early onward referral to an experienced knee surgeon is advocated.


Recurrent stroke secondary to late patent foramen ovale-closure device thrombus: a case report.
Percutaneous patent foramen ovale (PFO) closure has been well established in the secondary prevention of cryptogenic stroke with overall low rates of procedural complications. One such complication is PFO closure device thrombus formation which is now rarely reported with newer generation devices. We present the unusual case of a 59-year-old woman with myelofibrosis who developed late-onset recurrent embolic strokes related to Amplatzer PFO closure device thrombus whilst therapeutically anticoagulated on Warfarin. Surgical management was deemed too high risk and our patient was conservatively managed with enoxaparin. Serial transthoracic echocardiography demonstrated a reduction in thrombus size and the patient had no further neurological events. Overall, the risk of serious complications following percutaneous PFO closure, such as device-associated thrombus, remains low. The risk of thrombus formation in patients with hypercoagulable states is not well characterized. Despite good evidence for the efficacy in preventing recurrent cryptogenic stroke, the role of PFO closure in addition to anticoagulation is unclear. Given this uncertain benefit of PFO closure in anticoagulated patients and the unclear risk profile, patient selection, and thorough pre-procedural evaluation are vital when assessing the appropriateness of percutaneous PFO closure.


Ab initio calculations on SF2 and its low-lying cationic states: anharmonic Franck-Condon simulation of the UV photoelectron spectrum of SF2.
Geometry optimization calculations were carried out on the (approximate)X(1)A(1) state of SF2 and the (approximate)X(2)B(1), (approximate)A(2)A(1), (approximate)B(2)B(2), (approximate)C(2)B(2), (approximate)D(2)A(1), and (approximate)E(2)A(2) states of SF2(+) employing the restricted-spin coupled-cluster single-double plus perturbative triple excitation [RCCSD(T)] method and basis sets of up to the augmented correlation-consistent polarized quintuple-zeta [aug-cc-pV(5+d)Z] quality. Effects of core electron (S 2s(2)2p(6) and F 1s(2) electrons) correlation and basis set extension to the complete basis set limit on the computed minimum-energy geometries and relative electronic energies (adiabatic and vertical ionization energies) were investigated. RCCSD(T) potential energy functions (PEFs) were calculated for the (approximate)X(1)A(1) state of SF2 and the low-lying states of SF2(+) listed above employing the aug-cc-pV(5+d)Z and aug-cc-pV5Z basis sets for S and F, respectively. Anharmonic vibrational wave functions of these neutral and cationic states of SF2, and Franck-Condon (FC) factors of the lowest four one-electron allowed neutral photoionizations were computed employing the RCCSD(T) PEFs. Calculated FC factors with allowance for Duschinsky rotation and anharmonicity were used to simulate the first four photoelectron bands of SF2. The agreement between the simulated and observed first bands in the He I photoelectron spectrum reported by de Leeuw et al. [Chem. Phys. 34, 287 (1978)] is excellent. Our calculations largely support assignments made by de Leeuw et al. on the higher ionization energy bands of SF2.


Plasma concentrations of leptin in a bulimic patient.
Recently, the obese gene in the ob/ob mouse was cloned, along with its human homologue. The gene product leptin is important in the regulation of body weight. Excessive food intake during a binge might affect leptin synthesis. Alternatively, fluctuations in leptin synthesis might induce binge eating. Therefore, plasma leptin levels of a patient with bulimia nervosa were determined over a period of 48 hr in a natural setting. Amount, type, time of food intake, and binging and purging episodes were concomitantly assessed. Although binging and purging episodes were quite frequent, leptin levels remained stable and were neither related to food intake nor to binge episodes.


Versatile Large-Area Custom-Feature van der Waals Epitaxy of Topological Insulators.
As the focus of applied research in topological insulators (TI) evolves, the need to synthesize large-area TI films for practical device applications takes center stage. However, constructing scalable and adaptable processes for high-quality TI compounds remains a challenge. To this end, a versatile van der Waals epitaxy (vdWE) process for custom-feature bismuth telluro-sulfide TI growth and fabrication is presented, achieved through selective-area fluorination and modification of surface free-energy on mica. The TI features grow epitaxially in large single-crystal trigonal domains, exhibiting armchair or zigzag crystalline edges highly oriented with the underlying mica lattice and only two preferred domain orientations mirrored at 180°. As-grown feature thickness dependence on lateral dimensions and denuded zones at boundaries are observed, as explained by a semiempirical two-species surface migration model with robust estimates of growth parameters and elucidating the role of selective-area surface modification. Topological surface states contribute up to 60% of device conductance at room temperature, indicating excellent electronic quality. High-yield microfabrication and the adaptable vdWE growth mechanism with readily alterable precursor and substrate combinations lend the process versatility to realize crystalline TI synthesis in arbitrary shapes and arrays suitable for facile integration with processes ranging from rapid prototyping to scalable manufacturing.


Genomic Copy Number Variation Affecting Genes Involved in the Cell Cycle Pathway: Implications for Somatic Mosaicism.
Somatic genome variations (mosaicism) seem to represent a common mechanism for human intercellular/interindividual diversity in health and disease. However, origins and mechanisms of somatic mosaicism remain a matter of conjecture. Recently, it has been hypothesized that zygotic genomic variation naturally occurring in humans is likely to predispose to nonheritable genetic changes (aneuploidy) acquired during the lifetime through affecting cell cycle regulation, genome stability maintenance, and related pathways. Here, we have evaluated genomic copy number variation (CNV) in genes implicated in the cell cycle pathway (according to Kyoto Encyclopedia of Genes and Genomes/KEGG) within a cohort of patients with intellectual disability, autism, and/or epilepsy, in which the phenotype was not associated with genomic rearrangements altering this pathway. Benign CNVs affecting 20 genes of the cell cycle pathway were detected in 161 out of 255 patients (71.6%). Among them, 62 individuals exhibited >2 CNVs affecting the cell cycle pathway. Taking into account the number of individuals demonstrating CNV of these genes, a support for this hypothesis appears to be presented. Accordingly, we speculate that further studies of CNV burden across the genes implicated in related pathways might clarify whether zygotic genomic variation generates somatic mosaicism in health and disease.


[Congenital telangiectatic erythema (Bloom syndrome)].
"Congenital telangiectatic erythema" (Bloom's syndrome) is very rare; it is linked to a group of hereditary diseases and a common feature is cellular hypersensitivity to a variety of physical or chemical agents. The mode of transmission is autosomal-recessive. Characteristic criteria for Bloom syndrome are: consanguinity of the parents; androtropia; low birth weight, short stature (proportional); and persistent telangiectatic erythema in sun-exposed areas, sometimes with blistering. The syndrome is also associated with a facultative lack of antibodies. Of great importance is the high leukaemia morbidity among individuals with this syndrome; chromosomal aberrations and breakages play a significant role. Histological changes comprise an increase in dilated vessels in the upper dermis and damage and loss of elastic fibers. We give a review of Bloom's syndrome and present a case report.


Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening.
Since newborn screening (NBS) began in the 1960s, technological advances have enabled its expansion to include an increasing number of disorders. Recent developments now make it possible to sequence an infant's genome relatively quickly and economically. Clinical application of whole-exome and whole-genome sequencing is expanding at a rapid pace but presents many challenges. Its utility in NBS has yet to be demonstrated and its application in the pediatric population requires examination, not only for potential clinical benefits, but also for the unique ethical challenges it presents.


Iron substitution in the treatment of chronic heart failure.
Iron deficiency is a prevalent and clinically relevant comorbidity in up to 50% of patients with chronic heart failure (CHF). Iron deficiency in CHF patients is associated with impaired quality of life, reduced exercise capacity and increased mortality, irrespective of the presence of anaemia. It is diagnosed by determining circulating ferritin levels and transferrin saturation. Three randomised trials (CONFIRM-HF, FAIR-HF, and EFFECT-HF) of intravenous ferric carboxymaltose in the treatment of iron deficiency in CHF patients with reduced left ventricular ejection fraction demonstrated improvement of symptoms, functional capacity and quality of life. These beneficial effects were independent of the presence of anaemia. In addition, CONFIRM-HF and subsequent meta-analyses indicated that treatment of iron deficiency may reduce the rate of hospitalisations for worsening CHF. Oral iron is available at lower cost than intravenous iron, but its use did not translate into beneficial effects in CHF patients with iron deficiency. Large randomised trials designed to assess long-term clinical outcomes of iron treatment in CHF patients are pending. Current guidelines advise establishing evidence-based pharmacological and device therapy to improve symptoms and prognosis in patients with CHF. In addition, screening for iron deficiency is recommended. Intravenous ferric carboxymaltose should be considered for treating iron deficiency in ambulatory symptomatic patients with reduced left ventricular ejection fraction in order to alleviate heart failure symptoms, and to improve exercise capacity and quality of life.


Effect of Chirality on the Binding of Viologen Guests in Porphyrin Macrocycles.
As part of a project aimed at the development of chiral processive catalysts that can write information on a polymer chain we describe the synthesis of two optically active porphyrin macrocycles, which are prepared in 3 steps from an achiral precursor compound. Fluorescence and 1H-NMR studies show that one of the macrocycles displays selectivity in the binding of chiral viologen guest molecules.


The solvent-dependent shift of the amide I band of a fully solvated peptide as a local probe for the solvent composition in the peptide/solvent interface.
We determine the shift and line shape of the amide I band of a model AK peptide from molecular dynamics (MD) simulations of the peptide dissolved in methanol/water mixtures with varying composition. The IR spectra are determined from a transition dipole coupling exciton model. A simplified empirical model Hamiltonian is employed, which takes into account both the effect of hydrogen bonding and the intramolecular vibrational coupling. We consider a single isolated AK peptide in a mostly helical conformation, while the solvent is represented by 2600 methanol or water molecules, simulated for a pressure of 1 bar and a temperature of 300 K. Over the course of the simulations, minor reversible conformational changes at the termini are observed, which are found to only slightly affect the calculated spectral properties. Over the entire composition range, which varies from pure water to the pure methanol solvent, a monotonous shift towards higher frequency of the IR amide I band of about 8 wavenumbers is observed. This shift towards higher frequency is comparable to the shift found in preliminary experimental data also presented here on the amide I' band. The shift is found to be caused by two counter-compensating effects. An intramolecular red shift of about 1.2 wavenumbers occurs, due to stronger intramolecular hydrogen bonding in a methanol-rich environment. Dominating, however, is the intermolecular solvent-dependent shift towards higher frequency of about 10 wavenumbers, which is attributed to the less effective hydrogen-bond-donor capabilities of methanol compared to water. The importance of the solvent contribution to the IR shift, as well as the significantly different hydrogen formation capabilities of water and methanol, makes the amide I band sensitive to composition changes in the local environment close to the peptide/solvent interface. This allows, in principle, an experimental determination of the composition of the solvent in close proximity to the peptide surface. For the AK peptide case, we observe at low methanol concentrations a significantly enhanced methanol concentration at the peptide/solvent interface, supposedly promoted by the partially hydrophobic character of the AK peptide's solvent-accessible surface.


A case of primary lymphoid leukaemia in a horse.
Progressive leukaemic changes and a persistent anaemia were demonstrated in the blood of a 7 year old gelding, which had shown early signs of lowered performance and unthriftiness, and later developed dependent oedema and became dull and listless. The total leucocyte count, initially within the normal range although reflecting an absolute lymphocytosis, increased fourfold in 6 days from excessive lymphoid production involving predominantly the more immature cell types; lymphoblasts, prolymphocytes and large lymphocytes. The severity of the condition was confirmed by bone marrow biopsy.


Urinary Metabolomic Analysis of Prostate Cancer by UPLC-FTMS and UPLC-Ion Trap MSn.
Accumulative evidence suggests metabolic disorders correlate with prostate cancer. Metabolic profiling of urine allows the measurement of numerous metabolites simultaneously. This study set up a metabolomic platform consisting of UPLC-FTMS and UPLC-ion trap MSn for urine metabolome analysis. The platform improved retention time, mass accuracy, and signal stability. Additionally, the product ion spectrum obtained from ion trap MSn facilitated structure elucidation of candidate metabolites, especially when authentic standards were not available. Urine samples from six hernia patients and six BPH patients were used for the initial establishment of the analytic platform. This platform was further employed to analyze the urine samples of 27 PCa and 49 BPH patients. Choosing the upper and lower 16% of metabolites, 258 metabolite candidates were selected. Twenty-four of them with AUC values larger than 0.65 were further selected. Eighteen of the twenty-four features can be matched in METLIN and HMDB. Eleven of the eighteen features can be interpreted by MSn experiments. They were used for the combination achieving the best differential power. Finally, four metabolites were combined to reach the AUC value of 0.842 (CI 95, 0.7559 to 0.9279). This study demonstrates the urinary metabolomic analysis of prostate cancer and sheds light on future research.


The role of delta-opioid receptor subtypes in cocaine- and methamphetamine-induced place preferences.
The effects of delta-receptor antagonists on cocaine- and methamphetamine-induced place preferences were examined in rats. Cocaine- and methamphetamine-induced place preferences were significantly attenuated by naltrindole (NTI: a non-selective delta-opioid receptor antagonist). Furthermore, naltriben (NTB: a selective delta 2-opioid receptor antagonist), but not 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist), attenuated the cocaine- and methamphetamine-induced place preferences. These results suggest that delta-opioid receptors, particularly delta 2-opioid receptors, may be involved in the reinforcing effects of cocaine and methamphetamine.


Highly controlled immortal polymerization of β-butyrolactone by a dinuclear indium catalyst.
An ethoxy-bridged dinuclear indium catalyst was used for the ring opening polymerization of the cyclic ester β-butyrolactone to form the biodegradable polyester poly(hydroxybutyrate) (PHB). The catalyst shows remarkable activity and control during polymerization, allowing for formation of diblock polymers. Addition of high ratios of alcohols to the catalyst leads to fast chain transfer and immortal polymerization.


Nutritional status, tooth wear and quality of life in Brazilian schoolchildren.
To evaluate the correlation among nutritional status, tooth wear and quality of life in Brazilian schoolchildren. The study followed a cross-sectional design. Nutritional status was measured via anthropometry using BMI and tooth wear was measured using the Dental Wear Index; both these assessments were carried out by a trained recorder according to standard criteria. A modified version of the Child Oral Impacts on Daily Performances was used to assess quality of life. City of Bauru, in Brazil. A cluster sample of 396 schoolchildren (194 boys and 202 girls) aged 7-10 years. The anthropometric assessment showed similar situations for both sexes regarding underweight (31·40 % in boys and 30·20 % in girls) and overweight/obesity (33·96 % in boys and 33·17 % in girls). The underweight children showed a greater severity of tooth wear in the primary teeth (OR=0·72; CI 0·36, 1·42), although in the permanent dentition the obese children had a greater severity of tooth wear (OR=1·42; 95 % CI 0·31, 6·55). The tooth wear was correlated with age for both dentitions. Tooth wear in the primary and permanent dentition may be related to nutritional status. Tooth wear and obesity did not have a significant impact on the schoolchildren's perception of quality of life.


The relationship between pentosidine and hemodialysis-related connective tissue disorders.
Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA) and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on long-term hemodialysis (HD). Recently, it was suggested that advanced glycation end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are related to DRA. The aim of this study is to elucidate whether serum levels of pentosidine, which is an AGE, relate to the occurrence of DRA in patients with long-term HD. 127 end-stage renal failure patients, with DSA or CTS and undergoing HD, were examined. Serum pentosidine was measured by the HPLC method with column switching. Beta2m and intact parathyroid hormone (i-PTH) were measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA groups (patients in the DRA group had either DSA and/or CTS). There were no significant differences in the beta2m and i-PTH levels between any group. The duration of HD did not correlate with either pentosidine or beta2m levels, but did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The area under the ROC curve was the greatest for pentosidine. Serum beta2m levels were not related with the occurrence of DRA. The fact that serum pentosidine was higher in DRA than in non-DRA indicates that it has potential as an indicator of the occurrence of DRA in long-term HD patients.


[The beginning of the teaching of chemistry in Lorraine: the Royal College of Medicine and the Faculty of Medicine of Nancy (1752 and 1776)].
The faculty of medicine of the university created in Pont-à-Mousson in the second part of the XVIth century, transferred to Nancy in 1768, was not in possession of a chair of chemistry, but, in the middle of the XVIIIth century, it was interested by the development of this science. In Nancy, the Royal College of medicine, created by King Stanislas in 1752, disposed of a professor of chemistry since 1756, and also of a demonstrator who was one of the apothecaries of the town. In Metz, a course of this science occurred between 1756 and 1769 with the apothecary Thyrion. In 1776, the physician Henry Michel du Tennetar and the apothecary Pierre-François Nicolas opened a private course of chemistry, immediately transformed into a chair of the faculty of medicine. This chair will be maintained until Révolution. The personality and work of Michel du Tennetar and Nicolas, the circumstances and conditions of the creation of the chair, the inheritance of Michel, and the appointment of the demonstrator, also an apothecary, are successively described.


Anxiety, distress tolerance, and the relationship between complex posttraumatic stress disorder symptoms and alcohol use in veterans.
Little is known about whether distress tolerance and anxiety mediate the relationship between comorbid complex posttraumatic stress disorder (CPTSD) and alcohol use among military veterans. Here, we investigated the contribution of distress tolerance and anxiety on the strength of the CPTSD and alcohol use association. We hypothesized that the impact of a two-factor model of CPTSD derived from subscale scores on the International Trauma Questionnaire (ITQ)-namely ITQ PTSD and ITQ Disturbances in Self Organization (DSO; e.g., issues with affective regulation/self-belief and shame)-on alcohol use severity would be mediated by anxiety but not by distress tolerance. Participants included 403 community-dwelling United Kingdom (UK) veterans (91.64% male, Mage = 51.15 years, SD = 12.48) recruited as part of a larger, online study. Findings indicated that the influence of CPTSD symptoms on alcohol use severity was mediated by anxiety, not by distress tolerance, with greater relative impact due to ITQ DSO status than ITQ PTSD status. We identified the mediational influence of anxiety and distress tolerance on the association between CPTSD subscales and alcohol use in UK veterans. Interventions for anxiety may be adapted for reducing problematic alcohol use and the impact of CPTSD symptoms in veterans with comorbid PTSD and alcohol use disorder.


Prenatal behavior of multiples: implications for families and nurses.
Each twin and higher order multiple leads an extraordinary life before birth. The literature has revealed that the intrauterine environment differs for every multiple fetus and helps to shape the individuality of each multiple-birth child. From early in pregnancy, it appears that a multiple develops his or her own temperament and each set of multiples establishes an individualized pattern of tactile communication between or among themselves. The same behaviors, traits, and intermultiple interactions seen in pregnancy also have been observed in infancy and beyond. Intermultiple communication continues after birth, and preliminary evidence suggests that co-bedding assists the majority of newborns to make the transition from intrauterine to extrauterine life. The response of a multiple to the death of a co-multiple during pregnancy or after birth may be influenced by the relationship they shared in utero. Nurses and other health care providers have a role to play in informing multiple-birth parents about the latest knowledge, thereby assisting parents with the attachment process and specific parenting issues. In addition, nurses now have a solid foundation on which to create and implement care strategies that promote the healthy development of each multiple-birth infant and the intermultiple relationship.


Supported Palladium Catalyzed Carbonylative Coupling Reactions using Carbon Monoxide as C1 Source.
The carbonylative reactions of aryl halides, boronic acids, amines, activated alkene and alkynes under CO and supported palladium catalyzed conditions are very popular reactions for the synthesis of bioactive molecules, pharmaceuticals, polymers, peptides, intermediates and fine chemicals synthesis. Due to cost effectiveness and easy handling of recyclable supported palladium catalyst, it became more popular among researchers either working in academic institute or industry. In recent years, irrespective of poisoning effect of CO with palladium as major limitation, several advancements have been done through surface selection, designing and condition improvement to achieve high yield in the area of carbonylative coupling reactions. We hope this review will be helpful as a ready reference of last 20 years in the field of CO insertion reactions using diverse range of supported palladium catalysts under carbon monoxide or its sources as C1 source.


Primary non-Hodgkin's lymphoma of breast: a case report.
Primary breast lymphoma is a relatively uncommon neoplasm, majority being of B-cell origin. Mucosa associated lymphoid tissue (MALT) is one of the common types of breast lymphomas. Though cytologic diagnosis of breast lymphoma is an easy procedure and provides guidance for appropriate pre-operative management, it is often impossible to differentiate a low grade lymphoma from reactive proliferation. A similar difficulty was encountered in the present case, a 42 year old female with a breast lump. Fine needle aspiration cytology revealed a mixed lymphoid cell population. Lymphoepithelial lesions were identified histologically, and the majority of the cell population were confirmed as lymphoma cells of B-cell origin on immunohistochemistry. This case highlights the limitations of cytology and the importance of histological examination supported by immunohistochemistry for making a diagnosis of low grade primary breast lymphoma.


Effect of health insurance on direct hospitalisation costs for in-patients with ischaemic stroke in China.
Objectives The aim of the present study was to determine the direct medical costs of hospitalisations for ischaemic stroke (IS) in-patients with different types of health insurance in China and to analyse the demographic characteristics of hospitalised patients, based on data supplied by the China Health Insurance Research Association (CHIRA). Methods A nationwide and cross-sectional sample of IS in-patients with International Classifications of Diseases 10th Revision (ICD-10) Code I63 who were ensured under either the Basic Medical Insurance Scheme for Employees (BMISE) or the Basic Medical Insurance Scheme for Urban Residents (BMISUR) was extracted from the CHIRA claims database. A retrospective analysis was used with regard to patient demographics, total hospital charges and costs. Results Of the 49588 hospitalised patients who had been diagnosed with IS in the CHIRA claims database, 28850 (58.2%) were men (mean age 67.34 years) and 20738 (41.8%) were women (mean age 69.75 years). Of all patients, 40347 (81.4%) were insured by the BMISE, whereas 8724 (17.6%) were insured by the BMISUR; the mean age of these groups was 68.55 and 67.62 years respectively. For BMISE-insured in-patients, the cost per hospitalisation was RMB10131 (95% confidence interval (CI) 10014-10258), the cost per hospital day was RMB787 (95% CI 766-808), the out-of-pocket costs per patient were RMB2346 (95% CI 2303-2388) and the reimbursement rate was 74.61% (95% CI 74.48-74.73%). For BMISUR-insured in-patients the cost per hospitalisation was RMB7662 (95% CI 7473-7852), the cost per hospital day was RMB744 (95% CI 706-781), the out-of-pocket costs per patient were RMB3356 (95% CI 3258-3454) and the reimbursement rate was 56.46% (95% CI 56.08-56.84%). Conclusions Costs per hospitalisation, costs per hospital day and the reimbursement rate were higher for BMISE- than BMISUR-insured in-patients, but BMISE-insured patients had lower out-of-pocket costs. The financial burden was higher for BMISUR- than BMISE-insured in-patients. For BMISUR-insured in-patients, the out-of-pocket payment was 43.54% of total expenses, which means the government should increase the financial investment, raise reimbursement rates and set up differential reimbursements to meet the health needs of in-patients with different income levels. What is known about the topic? Cardiovascular and cerebrovascular diseases are major non-communicable diseases affecting the health of the Chinese population. The China Health Statistics Yearbook (2013) reported that across all in-patients, 195million (5.82%) had been discharged with a diagnosis of cerebrovascular disease. Of these, 118million had IS, accounting for 60.51% of all in-patients with cerebrovascular disease and 54.97% of hospitalisation costs for all cerebrovascular disease in-patients. After the two basic insurance systems, namely the BMISE and BMISUR, had been established, the out-of-pocket expenses for patients were reduced. However, to date there have been no studies investigating how the different types of health insurance (i.e. the BMISE and the BMISUR) affected the costs of treatment of IS in-patients in China. What does this paper add? This paper reports the direct costs for patients diagnosed with IS based on data supplied by the CHIRA. Direct hospitalisation costs depending on the type of insurance cover, age and gender were also evaluated. What are the implications for practitioners? The present study found that the personal financial burden of disease treatment was higher for in-patients insured under the BMISUR than BMISE. For in-patients insured under the BMISUR, the out-of-pocket payment was 43.54% of total expenses, which means the government should increase the financial investment, raise reimbursement rates and set up differential reimbursement rates to meet the health needs of patients with different incomes.


The effect of granulocyte colony-stimulating factor on engraftment in patients with lymphoproliferative malignancies and solid tumors undergoing autologous peripheral stem cell transplantation.
The effects of granulocyte colony-stimulating factor (G-CSF) and engraftment quality on the rate of hematopoietic system recovery were assessed in patients with solid tumors and lymphoproliferative diseases after autologous hematopoietic stem cell ransplantation. Treatment with autologous hematopoietic stem cell transplantation was performed in 40 patients for non- Hodgkin's lymphoma (n= 20), Hodgkin's lymphoma (n= 8), multiple myeloma (n= 8), and breast cancer (n=4). In 20 patients with solid tumors and ymphoproliferative diseases, treatment with autologous hematopoietic stem cell transplantation was followed by G-CSF therapy (experimental group). Another 20 patients with solid tumors and lymphoproliferative diseases were treated with autologous hematopoietic stem cell transplantation without G-CSF therapy (control group). The two patient groups were matched for age, sex, diagnosis, number of chemotherapy courses, and engraftment quality (nucleated cells or CD34+ cells). The experimental group received G-CSF in a dose of 5 μg/kg body weight subcutoneous from day 1 of autologous hematopoietic stem cell transplantation until leukocyte count increase to > 1.0 x 109/L over three consecutive days. Nonparametric tests (x2-test, median test, extended median test) were used in statistical analysis. The hematopoietic system showed rapid recovery. Leukocyte count > 1.0 x 109/L was recorded on median day 11 (range 8-21) in the experimental group vs median day 12 (range 9-16) in the control group; gra-nulocyte count > 0.5 x 109/L on median day 12 (range 8-23) vs day 14 (range 10-16) in the control group; and platelet count > 20 x 109/L on median day 13 (range 8-80) vs day 11 (range 7-15) in the control group. Differences between the two patient groups were not statistically significant. G-CSF therapy administered after autologous hematopoietic stem cell transplantation did not result in faster leukocyte, granulocyte or platelet recovery. The patients receiving a relatively lower number of cells showed the same rate of recovery as those who received a higher cell number. The number of CD34+ cells per kg body weight did not correlate with the rate of leukocyte, granulocyte or platelet recovery.


Strain Lattice Imprinting in Graphene by C60 Intercalation at the Graphene/Cu Interface.
Intercalation of C60 molecules at the graphene-substrate interface by annealing leads to amorphous and crystalline structures. A comparison of topography and electronic structure with wrinkles and moiré patterns confirms intercalation. The intercalated molecules imprint a local strain/deformation on the graphene layer whose magnitude is controlled by the intermolecular distance. The crystalline intercalated structure exhibits a superlattice peak in the local density of states. This work provides control of local strain in graphene.


Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis.
Forty two infants below the age of 2 years presenting with chronic non-infective diarrhoea and shown to have histologically proved colitis were investigated over a five year period. Allergic colitis was the most common cause of colitis, accounting for 62% of the cases. Other colitides diagnosed included: non-specific colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10% each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive family history and a personal history of atopy were obtained in 48% and 29% of the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in over 50% of the entire cohort of infants with colitis; 66% of those with severe combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two thirds of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. Thus infants with proved non-infective colitis as a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely that this minor deficiency of mucosa associated immunoglobulin production has a role in the pathogenesis of the colitic process.


Shape retaining injectable hydrogels for minimally invasive bulking.
Particle migration, poor shape definition and/or rapid resorption limit the success of current urethral bulking agents. We propose that shape defining porous scaffolds that allow cell infiltration and anchoring, and may be delivered in a minimally invasive manner may provide many advantageous features. Alginate hydrogels were prepared with varying degrees of covalent cross-linking and different pore characteristics. Dehydrated scaffolds were compressed into smaller, temporary forms, introduced into the dorsal subcutaneous space of CD-1 mice by minimally invasive delivery through a 10 gauge angiocatheter and rehydrated in situ with a saline solution delivered through the same catheter. Ionically cross-linked calcium alginate gel served as a control. Specimens were harvested at 2, 6, 12 and 24 weeks to evaluate implant shape retention and volume, cell infiltration and calcification, and the presence of an inflammatory response. A total of 90 scaffolds were implanted and 95% were recovered at the site of injection. All of these scaffolds successfully rehydrated and 80% recovered and maintained their original 3-dimensional shape for 6 months. Scaffold volume and tissue infiltration varied depending on the degree of alginate cross-linking. Highly cross-linked materials (20% and 35%) demonstrated the best volume maintenance with the latter facilitating the most tissue infiltration. The inflammatory response was minimal except with the 80% cross-linked material. Calcification was not observed in covalently cross-linked scaffolds. In contrast, 98% of calcium alginate implants were calcified. Shape retaining porous hydrogels meet many of the requirements necessary for a successful injectable bulking agent and offer advantages over currently used agents.


Biological attenuation of arsenic and iron in a continuous flow bioreactor treating acid mine drainage (AMD).
Passive water treatments based on biological attenuation can be effective for arsenic-rich acid mine drainage (AMD). However, the key factors driving the biological processes involved in this attenuation are not well-known. Here, the efficiency of arsenic (As) removal was investigated in a bench-scale continuous flow channel bioreactor treating As-rich AMD (∼30-40 mg L-1). In this bioreactor, As removal proceeds via the formation of biogenic precipitates consisting of iron- and arsenic-rich mineral phases encrusting a microbial biofilm. Ferrous iron (Fe(II)) oxidation and iron (Fe) and arsenic removal rates were monitored at two different water heights (4 and 25 mm) and with/without forced aeration. A maximum of 80% As removal was achieved within 500 min at the lowest water height. This operating condition promoted intense Fe(II) microbial oxidation and subsequent precipitation of As-bearing schwertmannite and amorphous ferric arsenate. Higher water height slowed down Fe(II) oxidation, Fe precipitation and As removal, in relation with limited oxygen transfer through the water column. The lower oxygen transfer at higher water height could be partly counteracted by aeration. The presence of an iridescent floating film that developed at the water surface was found to limit oxygen transfer to the water column and delayed Fe(II) oxidation, but did not affect As removal. The bacterial community structure in the biogenic precipitates in the bottom of the bioreactor differed from that of the inlet water and was influenced to some extent by water height and aeration. Although potential for microbial mediated As oxidation was revealed by the detection of aioA genes, removal of Fe and As was mainly attributable to microbial Fe oxidation activity. Increasing the proportion of dissolved As(V) in the inlet water improved As removal and favoured the formation of amorphous ferric arsenate over As-sorbed schwertmannite. This study proved the ability of this bioreactor-system to treat extreme As concentrations and may serve in the design of future in-situ bioremediation system able to treat As-rich AMD.


Near-perfect (>99%) dual-band absorption in the visible using ultrathin semiconducting gratings.
Electromagnetic perfect absorption entails impedance-matching between two adjacent media, which is often achieved through the excitation of photonic/plasmonic resonances in structures such as metamaterials. Recently, super absorption was achieved using a simple bi-layer configuration consisting of ultrathin lossy films. These structures have drawn rising interest due to the structural simplicity and mechanical stability; however, the relatively broadband absorption and weak angular dependence can limit its versatility in many technologies. In this work, we describe an alternative structure based on an ultrathin semiconducting (Ge) grating that features a dual-band near-perfect resonant absorption (99.4%) in the visible regime. An angular-insensitive resonance is attributed to strong interference inside the ultrathin grating layer, akin to the resonance obtained with a single ultrathin planar film, while an angular-sensitive resonance shows a much narrower linewidth and results from the diffraction-induced surface mode coupling. With an appropriately designed grating period and thickness, strong coherent coupling between the two modes can give rise to an avoided-crossing in the absorption spectra. Further, the angular-insensitive resonance can be tuned separately from the angularly sensitive one, yielding a single narrow-banded absorption in the visible regime and a broadband absorption resonance that is pushed into the near-infrared (NIR). Our design creates new opportunities for ultra-thin and ultra-compact photonic devices for application in technologies including image sensing, structural color-filtering and coherent thermal light-emission.


Safety and the probiotic potential of Bifidobacterium animalis CP-9.
Bifidobacterium animalis CP-9 was a commensal strain isolated from human breast milk. In this study, genetic and 90-day oral toxicity were assessed in rodents for its safety. Ames test as well as in vivo bone marrow micronucleus and spermatocyte chromosomal aberration were surveyed in mice. B. animalis CP-9 exhibited no mutagenic activity in the Ames test at the highest tested dosage (5000 µg/plate) with or without metabolic activation. No evidence of in vivo genetic toxicity was observed at the maximum tested dosage of 10 g/kg body weight (BW). Furthermore, there was no statistically significant difference of the biochemical and histological parameters in the rats administrated with B. animalis CP-9 at dosages of 0, 0.25, 0.5, or 1.5 g/kg BW/day. No indication of concern for pathogenicity was exhibited during evaluation of Bifidobacterium ssp. generally, or B. animalis specifically. It was noted that B. animalis CP-9 was able to survive in gastric acid-like and high bile salt environment, and showed strong adhesion to the intestinal epithelial cells, Caco-2. Intriguingly, B. animalis CP-9 decreased olic acid-induced triglyceral (TG) accumulation in the Caco-2 cells, and viable B. animalis CP-9 had a better bacteriostatic activity compared to another well-documented B. animalis ssp. lactis, BB-12. Based on the present study, B. animalis CP-9 can be a safe probiotic supplement and may improve the health of host. PRACTICAL APPLICATION: Although the health benefits of probiotics are well known, the safety of a probiotic product is acquired particularly for a long-term consumption. We conduct the safety of B. animalis CP-9 isolated from human breast milk, and demonstrate no toxicity concern in vitro and in vivo. Hence, B. animalis CP-9 powder can be used as a commercial and safe probiotic supplement with some health benefits.


Ratiometric Phosphorescent Probe for Thallium in Serum, Water, and Soil Samples Based on Long-Lived, Spectrally Resolved, Mn-Doped ZnSe Quantum Dots and Carbon Dots.
Thallium (Tl) is an extremely toxic heavy metal and exists in very low concentrations in the environment, but its sensing is largely underexplored as compared to its neighboring elements in the periodic table (especially mercury and lead). In this work, we developed a ratiometric phosphorescent nanoprobe for thallium detection based on Mn-doped ZnSe quantum dots (QDs) and water-soluble carbon dots (C-dots). Upon excitation with 360 nm, Mn-doped ZnSe QDs and C-dots can emit long-lived and spectrally resolved phosphorescence at 580 and 440 nm, respectively. In the presence of thallium, the phosphorescence emission from Mn-doped ZnSe QDs could be selectively quenched, while that from C-dots retained unchanged. Therefore, a ratiometric phosphorescent probe was thus developed, which can eliminate the potential influence from both background fluorescence and other analyte-independent external environment factors. Several other heavy metal ions caused interferences to thallium detection but could be efficiently masked with EDTA. The proposed method offered a detection limit of 1 μg/L, which is among the most sensitive probes ever reported. Successful application of this method for thallium detection in biological serum as well as in environmental water and soil samples was demonstrated.


Immunogenicity of a Candidate Ebola Hemorrhagic Fever Vaccine in Mice Based on Controlled In Vitro Expression of Ebolavirus Glycoprotein.
Ebolavirus (EBOV) is the etiology of Ebola hemorrhagic fever (EHF). A major EHF outbreak in 2014-2015 in West Africa claimed >11,000 lives. A licensed vaccine is not available for EHF, although several vaccines have undergone clinical trials. We developed a human adenovirus (Ad) serotype 5-based candidate EHF vaccine based on controlled expression of the EBOV (Makona strain) glycoprotein (GP) as the immunogen. Two clones, AdGP72 and AdGP75, and a control Ad515 vector, were generated and tested for protein expression in vitro and immunogenicity in mice. Eight groups of mice were immunized with three doses of buffer, Ad515, AdGP72, and AdGP75, by two different dose regimens. Three different antigens (AdGP75-infected Vero E6 cell extract and two baculovirus expressed EBOV GP antigens, namely, GP alone or GP with EBOV VP40) were used to evaluate the immune response. Expression studies indicated that full-length GP was cleaved into its component subunits when expressed in mammalian cells through the Ad vectors. Moreover, in coimmunoprecipitation studies, EBOV GP was found to be associated with VP40 when expressed in baculoviruses. The candidate vaccines were immunogenic in mice, as evaluated by enzyme-linked immunosorbent assay using mammalian- or baculovirus-derived antigens. Further characterization and development of the candidate vaccines are warranted.


Surgical prophylaxis with gentamicin and acute kidney injury: a systematic review and meta-analysis.
Gentamicin has been increasingly used instead of cephalosporins for surgical prophylaxis in an attempt to reduce the rate of "Clostridium difficile" infection. There are limited data regarding nephrotoxicity related to gentamicin in these patients. We have conducted a systematic review and meta-analysis to evaluate the risk of acute kidney injury (AKI) in gentamicin-containing surgical prophylactic regimens, compared to regimens without gentamicin, in several types of surgery. Electronic searches were performed using PubMed and Embase, including terms for "AKI, gentamicin, and surgical prophylaxis" with and without MeSH/EMTREE functions. Statistical analysis was then performed using a random-effect model; risk ratios (RR), risk differences (RD) and heterogeneity (I2) were calculated. Funnel plot was used for assessment of publication bias. Eleven studies with fifteen cohorts with 18,354 patients were included in the analysis. Subgroup analysis was performed according to surgery type. We have found that antibiotic prophylaxis with gentamicin containing regimen has significant risk for developing postoperative AKI in orthopedic surgery (RR 2.99; 95% CI: 1.84, 4.88). The results were inconclusive in other types of surgery. Funnel plot indicates potential publication bias. Gentamicin-induced AKI is significant in patients undergoing orthopedic surgery. Physicians should consider risks and benefits of using this regimen in individual patients.


SIMDOT-AbMe: microphysiologically based simulation tool for quantitative prediction of systemic and local bioavailability of targeted oral delivery formulations.
The purpose of this study was to develop a physiologically based simulation tool that is able to predict local as well as systemic bioavailability of 5-aminosalicylic acid (5-ASA)-targeted delivery formulations using the existing understanding of the transport and metabolism mechanisms of 5-ASA. The model accounts for active and passive transcellular transport (absorptive and efflux), passive paracellular transport, intestinal biotransformation, and systemic metabolism and clearance. The intestinal physiology was represented by transverse segments for ileum and proximal colon and longitudinal compartments for the microphysiology of the intestinal tissue. The tool, equipped with an optimization routine that enables tuning model parameters, was developed in Matlab and uses a user-friendly graphical interface for data input and output. Physiologic and kinetic model parameters were estimated either from literature monolayer transport studies using nonlinear curve fitting or obtained directly from the literature. 5-ASA clinical pharmacokinetic profiles of a once-daily (one 4-g/day dose) and twice-daily (two 2-g/day doses) dosing regimen were used to partially calibrate and validate the model, respectively. Simulation results showed that drug C(max) in the gut mucosal layers reached a higher level and was achieved sooner than in the systemic blood level. The computed relative local bioavailability with respect to the systemic bioavailability was 0.063. With use of the model, the relative local bioavailability of different formulations can be established for fast performance verification of new preparations based on measured systemic bioavailability. These types of models play a critical role in designing such preparations and rapidly assessing their effectiveness and will foster efficient experimental designs, saving time and resources.


Delaying of cataract through intervention of Hemidesmus indicus in STZ induced diabetic rats.
Hemidesmus indicus (L.) R. Br. was extensively used as hypoglycaemic agent and significance of this plant on secondary complications of diabetes remained unknown. The present study was to investigate the anti-cataractous activity of H. indicus against streptozotocin (STZ)-induced diabetic cataract in rodent model. Root extracts have been prepared and tested for inhibition of rat lens aldose reductase (AR) activity. In addition, its pharmacological potential has been investigated in STZ-induced diabetic cataract. Methanol extract of H. indicus-inhibited AR activity in vitro decreased the blood glucose levels, inhibited the AR activity and delayed the onset and progression of cataract in a dose-dependent manner in in vivo and the antioxidant markers have been normalised. Our results demonstrate that H. indicus has decrease the osmotic stress by inhibiting the AR activity and prevented the loss of antioxidants and delayed the progression of diabetic cataract in STZ-induced diabetic rats.


Hemodynamic effects of mebutamate in spontaneously hypertensive rats.
The acute hemodynamic effects of the antihypertensive agent mebutamate were evaluated in spontaneously hypertensive and normotensive Wistar rats. Arterial and venous pressures and cardiac output (electromagnetic flowmeter) were recorded in artificially ventilated, open-chest, ether-anesthetized animals before and after varying doses of mebutamate were injected intravenously. In both normotensive and hypertensive rats mebutamate produced a moderate decrease in arterial pressure which was associated with a reduction in both heart rate and cardiac output; total peripheral resistance remained unchanged. These data suggest that mebutamate may have therapuetic value in reducing arterial pressure in mild to moderately severe hypertensive patients.


On the pharmacokinetics of 2-chloro-2'-deoxyadenosine in humans.
The antitumoral effect of 2-chloro-2'-deoxyadenosine (CdA) in the treatment of lymphoproliferative diseases in general and of hairy cell leukemia in particular has recently been demonstrated. Detailed information on the pharmacokinetics of CdA, however, is lacking. The pharmacokinetics of CdA after 2- and 24-h infusions of 0.14 mg/kg was described in 12 patients with lymphoproliferative diseases using a newly developed high-performance liquid chromatography method. The plasma concentration data from individual patients were fitted to a two-compartment model with alpha- and beta-half-lives of 35 +/- 12 (mean +/- SD) min and 6.7 +/- 2.5 h, respectively. The volume of distribution was 9.2 +/- 5.4 liters/kg. The steady-state concentration of CdA during the 24-h infusion was 22.5 +/- 11.1 nM. The areas under the time versus concentration curves were 552 +/- 258 and 588 +/- 185 nM x h, respectively, for the 24- and 2-h infusions. The interindividual variability of the determinants of the plasma pharmacokinetics of CdA was small (the coefficients of variation were between 0.22 and 0.58). At 6.3 +/- 1.5 h after the start of the 2-h infusion, the concentration of CdA was the same as the steady-state concentration during the 24-h infusion. When the mean plasma concentrations of the 12 patients were fitted to a 3-compartment model, the half-lives of the alpha-, beta-, and tau-phases were 8 min, 1 h 6 min, and 6.3 h, respectively. The long terminal half-life of CdA after 2-h infusion supports the use of intermittent infusions.


Inhibition of P-TEFb by DRB suppresses SIRT1/CK2α pathway and enhances radiosensitivity of human cancer cells.
Positive transcription elongation factor-b (P-TEFb) is a complex containing CDK9 and a cyclin (T1, T2 or K). The effect of inhibition of P-TEFb by 5,6-dichloro-l-β-D-ribofuranosyl benzimidazole (DRB) on cell radiosensitivity and the underlying mechanisms were investigated. Six human cancer cell lines were subjected to (3)H-uridine incorporation, cell viability and clonogenic cell survival assays; cell-cycle redistribution and apoptosis assay; western blots and nuclear 53BP1 foci analysis after exposing the cells to DRB with/without γ-radiation. DRB suppressed colony formation and enhanced radiosensitivity of all cell lines. DRB caused a further increase in radiation-induced apoptosis and cell-cycle redistribution depending on p53 status. DRB prolonged the presence of radiation-induced nuclear p53 binding protein-1 (53BP1) foci and suppressed the expression of sirtuin-1 (SIRT1) and casein kinase 2-alpha (CK2α), suggesting an inhibition of DNA repair processes. Our findings indicate that DRB has the potential to increase the efficacy of radiotherapy and warrants further investigation using in vivo tumor models.


Australian consumer awareness of health benefits associated with vegetable consumption.
The present study investigated the perceived health benefits of specific vegetable consumption to guide the use of nutrition and health claims on vegetable marketing collateral. Free elicitation and consumer ranking data were collected through an online survey of 1000 adults from across Australia and analysed for the perceived importance of vegetables in the daily diet, number of serves consumed per day, knowledge about health-related benefits of specific vegetables and perceived health benefits of vegetable consumption. The importance of vegetables in the diet and daily vegetable consumption was higher in people from an English-speaking background, females, people aged 45 years and over and people living in non-metropolitan areas. Digestion was selected as the major health benefit from consumption of specific vegetables. However, understanding of the health benefits of specific vegetable consumption was relatively low among consumers. Half of the respondents were not sure of the health benefits associated with specific vegetables, except for carrots and spinach. Some respondents volunteered nutrient content or other information. There was no clear indication that consumers understand the specific health benefits conferred by consumption of vegetables. Nutrient and health benefit labelling therefore has the capacity to enhance knowledge of vegetable consumers. It is recommended that health benefit labelling be tailored to promote greater consumption of vegetables in those demographic groups where vegetable consumption was lower. The present study assists the Australian vegetable industry in helping consumers make more informed consumption choices.


Transoperative intravitreal dexamethasone implantation in patients with proliferative vitreoretinopathy.
To compare the anatomical results in patients with rhegmatogenous retinal detachment, at least grade B of proliferative vitreoretinopathy, and with a trans-surgical dexamethasone implant vs the control group. We also assessed the diminution of proliferative vitreoretinopathy and the final visual acuity (VA). The patients were evaluated clinically and with optical coherence tomography for 10 months. Logistic regression analyses were performed to evaluate the effect of the dexamethasone implant on retinal detachment. Correlational analyses were explored depending on the variables' distribution, and an independent samples t-test was used to compare the VA in both groups. The study included 38 eyes of patients with proliferative vitreoretinopathy: 18 with the implant and 20 for the control group. The evaluation of the main objective showed significant differences (p < 0.05) in the anatomical success between the two groups (61.1% vs. 20%, treatment vs. control); odds ratio of 6.29; 95% confidence interval: 1.5- 26.8; p = 0.013; Nagelkerke's R2 = 0.225. The t-test showed a significant difference in the final VA of the patients (t = 2.047; df = 36; p = 0.048; Cohen's d = 0.66). Retinal redetachment was less frequent, and better VA was observed, in patients with the dexamethasone implant in comparison with the control group.


The role of plant mycorrhizal type and status in modulating the relationship between plant and arbuscular mycorrhizal fungal communities.
Interactions between communities of plants and arbuscular mycorrhizal (AM) fungi shape fundamental ecosystem properties. Experimental evidence suggests that compositional changes in plant and AM fungal communities should be correlated, but empirical data from natural ecosystems are scarce. We investigated the dynamics of covariation between plant and AM fungal communities during three stages of grassland succession, and the biotic and abiotic factors shaping these dynamics. Plant communities were characterised using vegetation surveys. AM fungal communities were characterised by 454-sequencing of the small subunit rRNA gene and identification against the AM fungal reference database MaarjAM. AM fungal abundance was estimated using neutral-lipid fatty acids (NLFAs). Multivariate correlation analysis (Procrustes) revealed a significant relationship between plant and AM fungal community composition. The strength of plant-AM fungal correlation weakened during succession following cessation of grassland management, reflecting changes in the proportion of plants exhibiting different AM status. Plant-AM fungal correlation was strong when the abundance of obligate AM plants was high, and declined as the proportion of facultative AM plants increased. We conclude that the extent to which plants rely on AM symbiosis can determine how tightly communities of plants and AM fungi are interlinked, regulating community assembly of both symbiotic partners.


Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.
Mucoactive substances such as ambroxol, available in several countries as over-the-counter (OTC) medicines, are used for the treatment of acute and chronic bronchitis. This study was designed to evaluate the "real life" behavior of consumers with non-prescription access to an ambroxol cough syrup with special focus on tolerability and the pattern of product usage. Customers who bought the ambroxol syrup were recruited in 300 community pharmacies in Germany. Baseline data were collected from the participants in the pharmacy. Completing a self-administered questionnaire, participants provided information on tolerability, self-perceived effectiveness and usage pattern. 2,707 participants were recruited in 266 pharmacies. 2,664 questionnaires were evaluable. At baseline, the respondents reported a complex pattern of symptoms. Productive cough, congested airways, dry cough, cough irritation in the throat and soreness in the throat were the most common ones. 67 patients (2.5%) reported a total of 81 adverse events (AE) which were usually mild in nature and mostly affecting the gastrointestinal tract (n = 53) followed by skin and subcutaneous tissue disorders (n = 9). No serious or unknown AE were reported. In general, 97% of the participants assessed the safety as "very good" (51%) or "good" (46%). Overall, the respondents complied with the indications for use and the recommended dosages, with only 0.7% of the participants using the maximum daily dose. 92% of the patients assessed the self-perceived effectiveness as "very good" (29%) or "good" (63%) and 89% were willing to purchase this ambroxol cough syrup again. This study confirms that ambroxol is used according to the advice given in the patients' leaflet and supports the already established safety and efficacy of this product in acute bronchitis. It also demonstrates that the use of an OTC cough medication can be successfully monitored in a pharmacy-based cohort study.


Historical, psychopathological, neurological, and neuropsychological aspects of deficit schizophrenia: a multicenter study.
This multicenter study aimed to verify whether the historical and psychopathological characteristics of a large group of patients with deficit schizophrenia were consistent with those reported in previous studies. The authors also tested the hypothesis that neurological and neuropsychological indices sensitive to frontoparietal dysfunction, but not those sensitive to temporal lobe dysfunction, are more impaired in patients with deficit schizophrenia than in those with non-deficit schizophrenia. For each patient with deficit schizophrenia enrolled in the study, a matched subject with non-deficit schizophrenia was recruited. Historical, psychopathological, neurological, and neuropsychological evaluations were carried out for all patients. Patients with deficit schizophrenia, compared with patients with non-deficit schizophrenia, had a similar severity of positive symptoms and disorganization and less hostility. They had poorer premorbid adjustment during childhood and early adolescence and exhibited more impairment in general cognitive abilities. The deficit state was associated with impairment in sequencing of complex motor acts, which suggests frontoparietal dysfunction. Previous reports of differences in historical, psychopathological, and neuropsychological characteristics between patients with deficit schizophrenia and those with non-deficit schizophrenia were mostly supported by the present findings. Neurological findings suggest that frontoparietal functioning is more impaired in patients with deficit schizophrenia. Deficit schizophrenia might represent a neurodevelopmental subtype of schizophrenia in which significant behavioral and cognitive impairment since childhood compromises the development of basic capacities relevant to subsequent cognitive and social functioning.


The Synergistic Potential of Combining PD-1/PD-L1 Immune Checkpoint Inhibitors with NOD2 Agonists in Alzheimer's Disease Treatment.
Our research over the past decade has compellingly demonstrated the potential of Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor agonists in Alzheimer's disease (AD) treatment. These agonists facilitate the conversation of pro-inflammatory monocytes into patrolling monocytes, leading to the efficient clearance of amyloid-β (Aβ) in the AD-affected cerebrovascular system. This approach surpasses the efficacy of targeting Aβ formation, marking a significant shift in therapeutic strategies. Simultaneously, inhibitors of PD-1/PD-L1 immune check point or glycogen synthase kinase 3 beta (GSK3β), which modulates PD-1, have emerged as potent AD treatment modalities. PD-1 inhibitor exhibits a profound potential in monocytes' recruitment to the AD-afflicted brain. Recent evidence suggests that an integrated approach, combining the modulation of NOD2 and PD-1, could yield superior outcomes. This innovative combinatorial therapeutic approach leverages the potential of MDP to act as a catalyst for the conversion of inflammatory monocytes into patrolling monocytes, with the subsequent recruitment of these patrolling monocytes into the brain being stimulated by the PD-1 inhibitor. These therapeutic interventions are currently under preclinical investigation by pharmaceutical entities, underscoring the promise they hold. This research advocates for the modulation, rather than suppression, of the innate immune system as a promising pharmacological strategy in AD.


Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis.
Opioid-induced constipation (OIC) is a common problem in patients on chronic opioid therapy for cancer-related and non-cancer-related pain. Approved treatments for OIC are methylnaltrexone, naloxone, naloxegol, alvimopan, naldemedine, and lubiprostone. Since a meta-analysis performed in 2014, 2 new agents have been approved by the Food and Drug Administration for treatment of OIC (naloxegol and naldemedine). We conducted a search of the medical literature following the protocol outlined in the Cochrane Handbook for systematic review. We searched MEDLINE, EMBASE, EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials until March 2017 to identify randomized controlled trials of peripheral μ-opioid-receptor antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or naldemedine), lubiprostone, or prucalopride. Response to therapy was extracted in a dichotomous assessment as an overall response to therapy. The effect of pharmacologic therapies was pooled and reported as a relative risk (RR) of failure to respond to the treatment drug, with 95% CIs. We included 27 placebo-controlled trials in our meta-analysis (23 trials evaluated μ-opioid-receptor antagonists, 3 trials evaluated lubiprostone, and 1 trial evaluated prucalopride). In these trials, 5390 patients received a drug and 3491 received a placebo. Overall, μ-opioid-receptor antagonists, lubiprostone, and prucalopride were superior to placebo for the treatment of OIC, with a RR of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) and an overall number needed to treat of 5 (95% CI, 4-7). When restricted to only Food and Drug Administration-approved medications for OIC, the RR of failure to respond to therapy was 0.69 (95% CI, 0.62-0.77), with a number needed to treat of 5 (95% CI, 4-7). Sensitivity analyses and meta-regression performed to account for heterogeneity showed that treatment was more likely to be effective in study populations taking higher doses of opiates at baseline or refractory to laxatives. Study duration and prespecified primary outcome did not affect the RR of failure. Participants who received μ-opioid-receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo. In a systematic review and meta-analysis, we found μ-opioid-receptor antagonists to be safe and effective for the treatment of OIC. Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC.


Screening of some Tanzanian medicinal plants from Bunda district for antibacterial, antifungal and antiviral activities.
Extracts from 50 plant parts obtained from 39 different plants belonging to 22 families used to treat infectious diseases in Bunda district, Tanzania, were screened against twelve microorganisms, including the bacteria Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella typhimurium, the fungi Aspergillus niger, Candida albicans, and the viruses Herpes Simplex Virus type 1, Vesicular Stomatitis Virus T2, Coxsackie B2 and Semliki Forest A7. The highest activity was obtained for the n-hexane extract of Elaeodendron schlechteranum root bark against the Gram-positive bacteria Bacillus cereus (MIC 0.97 microg/ml and MBC 1.95 microg/ml) and Staphylococcus aureus (MIC 3.90 microg/ml and MBC 31.25 microg/ml). Gram-negative bacteria were less sensitive. Only Balanites aegyptiaca stem bark exhibited a high antifungal activity against Candida albicans (MIC 125 microg/ml and MFC 250 microg/ml). Extracts from four plants; Lannea schweinfurthii, Combretum adenogonium, Ficus sycomorus and Terminalia mollis showed strong antiviral activity with RF values of 10(3) and 10(4) against Herpes Simplex Virus type 1 at various concentrations. Our results support, at least in part, the use of most plants as claimed by traditional healers/informants especially against the Gram-positive bacteria Bacillus cereus and Staphylococcus aureus.


Physician visits in the United States for constipation: 1958 to 1986.
Since 1958, the National Disease and Therapeutic Index (NDTI) has provided annual statistics summarizing the frequency physicians throughout the United States are visited for different disease conditions. In our present study, these data were used to examine the epidemiology of constipation. Since NDTI statistics are available for a longer time period than other U.S. statistics, they might confirm or disprove the relevance of recent environmental changes on the occurrence of this disorder. The average number of physician visits for constipation in the United States was 2.5 million per year, corresponding to a prevalence of 1.2%. The largest number of these patients (31%) was seen by general and family practitioners, followed in declining order by internists (20%) and pediatricians (15%). Only 4% of all these patients was seen by gastroenterologists. Eight-five percent of these patients received a prescription for medication, with laxatives and cathartics being the most frequently prescribed drugs. Among physician visits for constipation, female prevalence was 1.6% compared with 0.8% for males (P less than 0.001). In both sexes, there was a significant age-related increase in the rate of physician visits, with the steepest rise from 1.3% to 4.1% occurring between the age groups 60-64 and over 65. From 1958 to 1986, the rate of all physician visits for constipation remained unchanged. However, during this time period, there was a twofold rise in physician visits for those patients ages 0-9 years, while a smooth decline occurred in all of the older age groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Health impact of human rights testimony: harming the most vulnerable?
Current legal efforts to document human rights violations typically include interviews in which survivors are asked to provide detailed descriptions of their traumatic experiences during a single meeting. Research on similar interview techniques used as part of a mental health treatment (eg, debriefing) has raised concerns that they might worsen mental health-more than doubling the risk of post-traumatic stress disorder in some studies. While controversy over the mental health impact of debriefing continues, debriefing treatments have been discontinued in most clinics nearly 2 decades ago. The purpose of this article is to promote the development and integration of preventative measures to limit potential mental health damage associated with legal endeavours to address human rights violations and international crimes. Given the recent growth of the field of global mental health and its current capacity to provide feasible, acceptable, effective care in low-resource settings, we propose a research agenda to identify the mental health impact of current human rights legal practices and test a model of scalable medicolegal care that minimises risk by integrating mental health monitoring and applying up-to-date models of trauma treatment, including multiple meeting sessions, as indicated. As the fields of global health, human rights law, international criminal law and transitional justice increasingly overlap in their efforts to assist communities affected by grave violence, we propose that synchronising efforts may offer important opportunities to improve mental health for survivors.


High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage.
Red blood cell transfusion is a life-saving intervention, and storage is a logistic necessity to make ~110 million units available for transfusion every year worldwide. However, storage in the blood bank is associated with a progressive metabolic decline, which correlates with the accumulation of morphological lesions, increased intra- and extra-vascular hemolysis upon transfusion, and altered oxygen binding/off-loading kinetics. Prior to storage, red blood cells are suspended in nutrient formulations known as additive solutions to prolong cellular viability. Despite a thorough expansion of knowledge regarding red blood cell biology over the past few decades, only a single new additive solution has been approved by the Food and Drug Administration this century, owing in part to the limited capacity for development of novel formulations. As a proof of principle, we leveraged a novel high-throughput metabolomics technology as a platform for rapid data-driven development and screening of novel additive solutions for blood storage under both normoxic and hypoxic conditions. To this end, we obtained leukocyte-filtered red blood cells (RBCs) and stored them under normoxic or hypoxic conditions in 96 well plates (containing polyvinylchloride plasticized with diethylhexylphthalate to concentrations comparable to full size storage units) in the presence of an additive solution supplemented with six different compounds. To inform this data-driven strategy, we relied on previously identified metabolic markers of the RBC storage lesion that associates with measures of hemolysis and post-transfusion recovery, which are the FDA gold standards to predict stored blood quality, as well as and metabolic predictors of oxygen binding/off-loading parameters. Direct quantitation of these predictors of RBC storage quality were used here-along with detailed pathway analysis of central energy and redox metabolism-as a decision-making tool to screen novel additive formulations in a multiplexed fashion. Candidate supplements are shown here that boost-specific pathways. These metabolic effects are only in part dependent on the SO2 storage conditions. Through this platform, we anticipate testing thousands of novel additives and combinations thereof in the upcoming months.


Novel cryoprecipitate for wound healing and skin grafts in rats.
The authors sought to evaluate the ability of locally administered enhanced cryoprecipitate (eCryo) to improve the wound healing of split thickness skin grafts (STSG) and their donor sites. An STSG (5 x 5 cm) was harvested on the back of 30 rats and divided into four areas that were then treated in one of the following groups: A: 'standard' dressing without STSG; B: eCryo without STSG; C: eCryo with STSG coverage and D: STSG alone. Macroscopic and histological assessments (histomorphometric grading scale and cellular composition) were evaluated at days 7, 14, 21 and 28 for wound healing. All wound beds as well as STSGs healed well without any complications. Eighty per cent of the STSG showed a histological graft take of >75% after 28 days. There were no statistically significant differences of macroscopic or histological results between the groups at any time point. Preparation of eCryo is easy and effective. Its use as an adhesive for STSGs is safe and shows similar results as controls. The theoretical benefits of eCryo did not show significant differences. Possible reasons as well as important findings for future research on wound healing are discussed.


Somatic structural variations in pediatric brain tumors.
Pediatrics brain tumors are the second most frequent malignancy in children, and the most common cause of cancer-related deaths in both the 0-14-year and the 15-24-year age group. Although, pediatrics high-grade glioma (pHGG) is a histologically similar tumor to that arising in adults, these are distinct biological diseases, differing in copy number profiles and driver genetic alterations. Recent sequencing initiatives have conclusively shown the existence of subgroups of HGG marked by distinct driver mutations, which are significantly enriched in young children (H3F3A K27M), teenagers and young adults (H3F3A G34R/V), and middle- aged adults (IDH1/2). Structural rearrangements resulting in novel fusion genes are strongly associated with cancer, and numerous examples exist in both adult and childhood malignancies. Although, only few have been described in pHGG. Structural variants (SV) frequently result in chimeric proteins targetable by novel therapeutic approaches, an outcome desperately needed in pHGG.


Parsonage-Turner Syndrome Following COVID-19 Vaccination: MR Neurography.
Vaccination is one of the several known triggers of Parsonage-Turner syndrome (PTS). This case series describes two individuals with clinical presentations of PTS whose symptoms began 13 hours and 18 days following receipt of the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 COVID-19 vaccine, respectively. The diagnosis of PTS was confirmed by using both electrodiagnostic testing and 3.0-T MR neurography. Although research is needed to understand the association between PTS and COVID-19 vaccination, MR neurography may be used to help confirm suspected cases of PTS as COVID-19 vaccines continue to be distributed worldwide.


[Evaluation of a Visually-Read Rapid Antigen Test Kit (SGA V-Chek) for Detection of SARS-CoV-2 Virus].
Although the reverse transcriptase polymerase chain reaction (RT-PCR) method has been accepted as the reference method in the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA, it requires special laboratory conditions, complicated and expensive laboratory instruments, competent laboratory staff and long testing duration. Antigen testing methods such as enzyme immunoassay, fluorescent antibody and visually-read immunochromatographic rapid antigen detection (RAD) tests eliminated the above mentioned disadvantages of the RT-PCR. The aim of this study was to determine the performance of a RAD test kit (V-Chek, SGA Ltd, Ankara, Turkey). Two paired nasopharyngeal swabs were collected from each patient, and one of them was used for the RAD test, while the other one (different swab) was used to perform the RT-PCR test. SARS CoV-2 Double Gene RT-PCR kit (Bioeksen, Turkey) was used for RNA amplification on the Light Cycler 480 plate-based RT-PCR instrument (Roche, Switzerland). The SARS-CoV-2 double gene RT-PCR kit targeting the SARS-CoV-2 specific N (nucleocapsid) and Orf1ab gene regions was used for RNA amplification. The human RNaseP gene was used for nucleic acid extraction and inhibition control. The shape of the growth curves was examined and the non-sigmoidal curves were recorded as "negative". Sigmoidal curves with cycle threshold (Ct) <38 were evaluated as "positive". The Ct values of all positive results were recorded. V-Chek RAD test kit uses a colloidal gold enhanced double antibody sandwich type antigen test kit. A SARS-CoV-2 positive specimen produces a distinct color band in the test region, formed by the specific antibody-antigen colored conjugate complex. A positive or negative result is indicated by a colored line appearance on the test region. A colored line appears in the control region, independent of the SARS-CoV-2 presence. The result is visually read 10 minutes after the last drop of the sample liquid is dispensed into the sample well. Specificity and sensitivity values were calculated accepting the RT-PCR results as a standard. Agreement between two different techniques was assessed using Cohen's kappa score. 110 patients were enrolled in this study; 34 (30.9 %) of these patients had positive RT-PCR samples, with the mean of Ct values of 25.8 (95% CI= 24.1-27.5), median of Ct values of 26. In our study population, the overall sensitivity was 61.8% (95% CI= 45.4-78.1), and specificity was 100%. Taking RT-PCR as reference, Cohen's kappa score for the antigen test was 0.691. Fisher's exact test was p<0.001. In conclusion, the RAD kit used in the study determined to be useful for the rapid identification of COVID-19 patients. However, a negative result does not eliminate the possibility of COVID-19 infection and should be confirmed by RT-PCR and clinical findings.


Zoledronic acid: monoclinic and triclinic polymorphs from powder diffraction data.
The crystal structures of the monoclinic and triclinic polymorphs of zoledronic acid, C5H10N2O7P2, have been established from laboratory powder X-ray diffraction data. The molecules in both polymorphs are described as zwitterions, namely 1-(2-hydroxy-2-phosphonato-2-phosphonoethyl)-1H-imidazol-3-ium. Strong intermolecular hydrogen bonds (with donor-acceptor distances of 2.60 Å or less) link the molecules into layers, parallel to the (100) plane in the monoclinic polymorph and to the (1-10) plane in the triclinic polymorph. The phosphonic acid groups form the inner side of each layer, while the imidazolium groups lie to the outside of the layer, protruding in opposite directions. In both polymorphs, layers related by translation along [100] interact through weak hydrogen bonds (with donor-acceptor distances greater than 2.70 Å), forming three-dimensional layered structures. In the monoclinic polymorph, there are hydrogen-bonded centrosymmetric dimers linked by four strong O-H...O hydrogen bonds, which are not present in the triclinic polymorph.


The effect of hypertonic ointments on corneal alkali burns.
Alkali-burned rabbit corneas were treated with 40% glucose or 5% sodium chloride ophthalmic ointments 3 times daily for 6 weeks and examined clinically and histologically. Treatment with hypertonic ointment as compared to untreated controls demonstrated decreased corneal neovascularization and ulceration. The possible nutritional advantage of hypertonic glucose did not prove beneficial compared to hypertonic sodium chloride.


Empirical Compression Model of Ultra-High-Performance Concrete Considering the Effect of Cement Hydration on Particle Packing Characteristics.
The mix design of UHPC has always been based on a large number of experiments; in order to reduce the number of repeated experiments, in this study, silica fume (SF), fly ash (FA), and limestone powder (LP) were used as the raw materials to conduct 15 groups of experiments to determine the particle size distribution (PSD) properties of UHPC. A model of multi-component hydration based on the SF, FA, and LP pozzolanic reactions was devised to quantify the rate and total heat release during the hydration process. Additionally, a microscopic pore development model, which was based on the accumulation of hydration products, was established to measure the effect of these products on the particle-packing properties. Utilizing this model, a UHPC strength prediction technique was formulated to precisely forecast the compressive strength based on a restricted experimental data set. The applicability of this prediction method was verified using 15 sets of existing experimental data along with the data collected from 4 research articles. The results show that the prediction method can predict the strength values of different mix proportions with an accuracy rate of over 80%.


Characterization and differential expression patterns of conserved microRNAs and mRNAs in three genders of the rice field eel (Monopterus albus).
MicroRNAs (miRNAs) are endogenous small RNAs that can regulate target mRNAs by binding to their sequences in the 3' untranslated region. The expression of miRNAs and their biogenetic pathway are involved in sexual differentiation and in the regulation of the development of germ cells and gonadal somatic cells. The rice field eel (Monopterus albus) undergoes a natural sexual transformation from female to male via an intersex stage during its life cycle. To investigate the molecular mechanisms of this sexual transformation, miRNAs present in the different sexual stages of the rice field eel were identified by high-throughput sequencing technology. A significantly differential expression among the 3 genders (p < 0.001) was observed for 48 unique miRNAs and 3 miRNAs*. Only 9 unique miRNAs showed a more than 8-fold change in their expression among the 3 genders, including mal-miR-430a and mal-miR-430c which were higher in females than in males. However, mal-miR-430b was only detected in males. Several potential miRNA target genes (cyp19a, cyp19b, nr5a1b, foxl2 amh, and vasa) were also investigated. Real-time RT-PCR demonstrated highly specific expression patterns of these genes in the 3 genders of the rice field eel. Many of these genes are targets of mal-miR-430b according to the TargetScan and miRTarBase. These results suggest that the miR-430 family may be involved in the sexual transformation of the rice field eel.


Milestones in the development of Nordic general practice*.
The common history and development of Nordic family medicine is important and interesting. This paper looks back on the aspects and factors influencing academic family medicine in the Nordic countries and especially the central position of the Nordic Congresses and the Scandinavian Journal of Primary Health Care. The importance of pioneers and bringing people together is emphasized. More than 30 years of Nordic academic family medicine has indeed had an incredible impact and has initiated development from only a few people to become world leading.