Improving performance of a tandem simulated moving bed process for sugar separation by making a difference in the adsorbents and the column lengths of the two subordinate simulated moving bed units.
A tandem simulated moving bed (SMB) process for removal of sulfuric acid and acetic acid from sugars has been developed previously. This process consisted of two four-zone SMB units (Ring I and Ring II), in which the same adsorbent (Dowex99 resin) and the same column length were used. To improve the performance of such a tandem SMB process for sugar separation, it is worth adopting the strategy of making a difference between the column lengths of Ring I and Ring II. The results showed that such strategy could allow the adsorbent beds of both Ring I and Ring II to be fully utilized at the same time, which was impracticable in the previous tandem SMB mode. As a result, the tandem SMB based on such strategy could achieve higher productivity than the previous tandem SMB mode. In addition, the use of different adsorbents (Amberchrom-CG161C in Ring I and Dowex99 in Ring II) was proposed as the second strategy, which was confirmed to be highly effective in improving the productivity of the tandem SMB for sugar separation. Finally, a third strategy was proposed by combing the first and the second strategies. It was found that compared to the previous tandem SMB mode, the third strategy led to more than eleven times the productivity under the constraint of pressure drop ≤100 psi. This was mostly because the third strategy had a remarkable advantage over the previous tandem SMB mode in the aspects of bed utilization and selectivities, which stemmed from the use of different column lengths and the use of different adsorbents respectively.


Interactive effects of peptidoleukotrienes and histamine on microvascular permeability and their involvement in experimental cutaneous and conjunctival immediate hypersensitivity.
The involvement of peptidoleukotrienes (LTs) in mediating the increase in microvascular permeability associated with experimental cutaneous immediate hypersensitivity was studied by examining the effect of SK&F 104353, a potent and selective LT-antagonist, on the response evoked by graded, intradermal injections of antigen. SK&F 104353, employed at doses that profoundly blocked LTC4, LTD4 and LTE4 responses, significantly reduced the response produced by experimental cutaneous immediate hypersensitivity. The response to the lowest antigen dose (0.1 microgram) was, however, entirely insusceptible to SK&F 104353. The effect of SK&F 104353 was also examined in combination with a pyrilamine-cimetidine dosing regimen sufficient to remove the histaminergic component of cutaneous immediate hypersensitivity. The non-histaminergic component associated with higher antigen doses (10 and 100 micrograms) was significantly reduced but not abolished by SK&F 104353; the non-histaminergic component associated with low antigen doses (0.1 and 1 microgram) was not susceptible to SK&F 104353. Thus, the increase in cutaneous microvascular permeability evoked by immediate hypersensitivity appears to comprise three components: (1) A histaminergic response apparent for all antigen doses; (2) a LT-mediated component which is manifest in response to high antigen doses; (3) a third, unidentified component that is present for the entire antigen dose-range but contributes less to the overall response when high antigen doses are used. A distinct non-histaminergic, non-leukotriene mediated component was not a feature of conjunctival immediate hypersensitivity. SK&F 104353 administered in combinatio with pyrilamine-cimetidine virtually abolished the response with a small residual remaining only for the highest antigen dose. In further contrast to cutaneous immediate hypersensitivity, SK&F 104353 alone was comparatively ineffective in type 1 allergic conjunctivitis. This difference in susceptibility to SK&F 104353 appears to reflect the type of histamine-LTD4 interactive effect on microvascular permeability. Histamine and LTD4 were additive in terms of cutaneous microvascular permeability. In the conjunctiva, histamine and LTD4 appeared mutually exclusive in that the level of response produced by the combination tended not to exceed that of the single component which caused the greater effect.


[Immortalization of human dental pulp stem cells caused by transferring hTERT gene].
To establish an immortalized human dental pulp stem cell line used for basic and clinical research of oral science. Human telomerase reverse transcriptase (hTERT) cDNA was transferred into human dental pulp stem cells (hDPSCs) by lentivirus. The resultant stable clones reproduced successively and the expression of hTERT was identified. The hTERT gene was transferred into human dental pulp stem cells successfully. The transformed cells expressed telomerase activity and divided vigorously. p35 had been obtained so far. The hDPSCs can be immortalized by transferring exogenous hTERT gene to constitute telomerase activity.


Simulation of psychosis by continuous delivery of phencyclidine from controlled-release polymer implants.
To simulate psychosis in rats we have developed a method for the continuous delivery of phencyclidine (PCP) using implantable controlled-release polymers. PCP polymer implants produced deficits in latent inhibition which do not occur after repeated bolus injections. PCP implanted rats were also devoid of any anxiogenic signs, motoric hyperactivity and learning acquisition which can be seen in rats receiving daily bolus injections of a comparable PCP dose. This behavioral double-dissociation of the two modes of PCP application was accompanied by respective neurochemical changes. PCP binding sites were reduced in both striatum and hippocampus, but in the hippocampus, loss of PCP binding sites was more severe following pulsatile PCP administration. Morphological assessment revealed a significant shrinkage of the CA3 region in hippocampus in both groups. Pharmacokinetic analysis showed that the maximum PCP concentration in the brain after bolus injections was 10-fold above the PCP implants.


Spinal cord injury or spinal anesthesia eliminates seizures in myelin-deficient rats.
The generalized tonic seizures that occur in myelin-deficient rats can be eliminated temporarily by spinal cord injury or spinal anesthesia. These observations imply that the seizures in this mutant can be triggered by activity in the spinal cord. The results are consistent with an earlier proposal that axons in myelin-deficient CNS fiber tracts can interact to produce abnormal excitation.


The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.
DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occurs by homologous recombination, which relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution.


[Influence of disease prognosis and age on the radiation risk from diagnostic nuclear medicine (bone scintigraphy as an example)].
Of the study was to assess the influence of the patient age and the survival of patients undergoing bone scintigraphy on the calculations of the theoretical lifetime loss. The evaluated data set included 216 patients undergoing a bone scan for the first time in 1980. From 182 patients a study end point (either the date of death, or existing registration in the German resident office on the 31.12.1995) was obtained. The theoretical life time loss was based on the formalism previously presented by Schicha und Wellner (13). In 74% of the examined patients a malignant disease was present. 28% of the patients had died within one year of the examination. At the end of the follow-up period, of at least 15 years, 58% of the patients were deceased. The theoretical lifetime loss due to radiation exposure within this specified patient group was estimated to be 0.152 d/mSv. Assuming an age distribution of the general population and statistically derived life expectancy, this value should be 0.437 d/mSv. The estimates regarding the risk of diagnostic procedures using ionizing radiation should take into account the limited life expectancy of patients in hospitals.


Angiolipoma of the spinal cord. Magnetic resonance imaging and microsurgical management.
Radiologic diagnosis of intramedullary lipomas has been unreliable for a long time and many of these tumors have not been recognized. The introduction of computed tomography, and lately of magnetic resonance imaging, has led to great progress in the accurate identification of spinal cord tumors as well as in the recognition of type specificity of these lesions. An evaluation of the diagnostic value of magnetic resonance imaging and microsurgical technique for the optimal therapeutic outcome is discussed.


A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes.
This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented. Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks. For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments. IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.


Effect of dose and route of administration of thyroid releasing hormone (TRH) on the concentration of prolactin (PRL) and thyroxine (T4) in cyclic gilts.
Our objective was to examine the ability of thyroid releasing hormone (TRH) to stimulate not only the release of the thyroid hormones, but also prolactin (PRL) in the female pig. An experiment was conducted to determine the effect of dose and route of administration of TRH on the concentration of PRL and thyroxine (T4) in cyclic gilts. Six gilts were injected with 0, 5, 25, 125, and 625 micrograms TRH and fed 0, 5, 2.5, 12.5 and 62.5 mg TRH. Gilts received TRH once daily. During the 10-day treatment period, route of TRH administration alternated between i.v. injection and feeding. The dose of TRH progressed from the lowest to the highest. Blood samples were taken prior to TRH injection and thereafter at 15-min intervals for 3 hr. Sampling continued for an additional 3 hr at 30-min intervals when TRH was fed. Concentrations of PRL and T4 were determined by radioimmunoassay. Intravenous injection of gilts with 125 and 625 micrograms TRH resulted in an increase in PRL from 0 to 15 min (P less than .05). All doses of TRH given i.v. elevated T4 over a 2-hr period (P less than .01). TRH failed to increase PRL when TRH was fed (P greater than .5). The feeding of 62.5 mg TRH elevated T4 from 0 to 6 hr (P less than .01). Thus, TRH injection increased PRL rapidly and T4 gradually. When TRH was fed, only a gradual elevation in T4 was observed. We conclude that TRH can elicit the release of both PRL and T4 in the cyclic gilt, but magnitude and duration of the PRL and T4 response depends on the dose and route of TRH administration.


Leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury.
LTB4 is classified as a leukotriene (LT), a group of lipid mediators that are derived from arachidonic acid. It is recognized that leukotrienes are involved in the pathogenesis of many diseases, including peripheral inflammatory pain. However, little is known about the effects of leukotrienes on the spinal dorsal horn during neuropathic pain. Previously, we reported that there was increased expression of 5-lipoxygenase (5-LO) at spinal microglia, and the leukotriene B4 receptor 1 (BLT1), a high affinity receptor of LTB4, in spinal neurons in spared nerve injury (SNI) model rats. In the present study, we examined the effects of LTB4 on spinal dorsal horn neurons in both naïve and SNI model rats using patch-clamp methods. Bath application of LTB4 did not change AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) or membrane potentials. However, we found that LTB4 enhanced the amplitude of NMDA receptor-mediated sEPSCs and significantly increased exogenous NMDA-induced inward currents in SNI model rats. This increase of inward currents could be inhibited by a selective LTB4 antagonist, U75302, as well as a GDP-β-S, a G-protein inhibitor. These results indicate that both increased LTB4 from spinal microglia or increased BLT1 in spinal neurons after peripheral nerve injury can enhance the activity of NMDA receptors through intracellular G-proteins in spinal dorsal horn neurons. Our findings showed that LTB4, which may originate from microglia, can activate BLT1 receptors which are expressed on the membrane of spinal dorsal horn neurons during neuropathic pain. This glia-neuron interaction induces the enhancement of NMDA currents through intracellular G-proteins. The enhancement of NMDA receptor sensitivity of dorsal horn neurons may lead to central sensitization, leading to mechanical pain hypersensitivity.


Mesenchymal stromal cells for tissue-engineered tissue and organ replacements.
Mesenchymal stromal cells (MSCs), a rare heterogeneous subset of pluripotent stromal cells that can be easily isolated from different adult tissues, in vitro expanded and differentiated into multiple lineages, are immune privileged and, more important, display immunomodulatory capacities. Because of this, they are the preferred cell source in tissue-engineered replacements, not only in autogeneic conditions, where they do not evoke any immune response, but especially in the setting of allogeneic organ and tissue replacements. However, more preclinical and clinical studies are requested to completely understand MSC's immune biology and possible clinical applications. We herein review the immunogenicity and immunomodulatory properties of MSCs, their possible mechanisms and potential clinical use for tissue-engineered organ and tissue replacement.


Primary immunodeficiencies: a 27-year review at a tertiary paediatric hospital in Cape Town, South Africa.
The epidemiology of primary immunodeficiencies (PID) is not well documented in Africa. The objective of this study was to describe the spectrum of PID at a tertiary paediatric centre in South Africa. A retrospective study was conducted on 168 patients diagnosed with PID from 1983 to 2009. Over the study period, antibody deficiencies predominated (51%) followed by well-defined syndromes (24%). Common variable immunodeficiency was the commonest antibody deficiency. The mean age of diagnosis was 51 months overall but decreased significantly to 35 months over the last 9 years. Recurrent infections were the most common presenting complaint (74%). The overall mortality rate was 25% while combined immunodeficiencies accounted for 40% of the deaths. The spectrum of PID in South Africa was similar to international trends. The declining mean age of diagnosis indicated improved recognition of PID. Future research should focus on identifying children with PID more effectively.


BraneMF: integration of biological networks for functional analysis of proteins.
The cellular system of a living organism is composed of interacting bio-molecules that control cellular processes at multiple levels. Their correspondences are represented by tightly regulated molecular networks. The increase of omics technologies has favored the generation of large-scale disparate data and the consequent demand for simultaneously using molecular and functional interaction networks: gene co-expression, protein-protein interaction (PPI), genetic interaction and metabolic networks. They are rich sources of information at different molecular levels, and their effective integration is essential to understand cell functioning and their building blocks (proteins). Therefore, it is necessary to obtain informative representations of proteins and their proximity, that are not fully captured by features extracted directly from a single informational level. We propose BraneMF, a novel random walk-based matrix factorization method for learning node representation in a multilayer network, with application to omics data integration. We test BraneMF with PPI networks of Saccharomyces cerevisiae, a well-studied yeast model organism. We demonstrate the applicability of the learned features for essential multi-omics inference tasks: clustering, function and PPI prediction. We compare it to the state-of-the-art integration methods for multilayer networks. BraneMF outperforms baseline methods by achieving high prediction scores for a variety of downstream tasks. The robustness of results is assessed by an extensive parameter sensitivity analysis. BraneMF's code is freely available at: https://github.com/Surabhivj/BraneMF, along with datasets, embeddings and result files. Supplementary data are available at Bioinformatics online.


[Quantitative description of the process of cellular radiation inactivation. IX. Remarks on the relative biological effectiveness of ionizing radiations in the reproductive death of diploid and polyploid cells].
The relative biological effectiveness (RBE) has been considered for three kinds of cell radiation damages: subdamages (sublethals), one-track, and two-track lethal damages. In contrast to the "dual theory", which postulates the square relation between the lethal damage yield and the specific energy, it is assumed that the one-track lethal yield is linearly related to the specific energy per cell nucleus. As a result, the identical dependence has been obtained of both one-track lethals and subdamages on specific energy and absorbed dose. It is established that RBE for all three kinds of damages does not depend on the radiation dose. It is shown that RBE for subdamages and one-track lethals depends on LET of radiation only, and involves molecular parameters of sensitive cell structures. Within the limits of this assumption, the relations are general for all the types of eukaryotic cells. These can be used for a further development of the RBE theory, with spectra of LET, the track structure of charged particles, the contribution of delta-electrons etc being taken into consideration.


Variations in chemical composition of common buckwheat (Fagopyrum esculentum Moench) as a result of different environmental conditions.
Common buckwheat (Fagopyrum esculentum Moench) is a pseudo cereal that is gaining interest in the world. The chemical profile of common buckwheat determines its high nutritional and health-promoting value. The accumulation of these valuable ingredients depends on many factors, such as: variety, location of cultivation and related weather and agrotechnical conditions. Due to the growing interest in common buckwheat as a natural plant material for food production, it is important to know the factors affecting the quantitative and qualitative composition of its grains. The aim of the research was to determine the effect of the genotype (G), environment (E) and G × E interaction on the content of nutrients (protein, starch, ash, lipids) and bioactive components [dietary fiber (DF), total phenolic content (TPC)] in the common buckwheat grains. The study covered four cultivars grown in three locations for three consecutive vegetation seasons (2016/2017, 2017/2018, 2018/2019). Based on the obtained results, a significant influence of the environment and G × E interaction on the content of the studied parameters was found. The greatest impact on the diversity of the content of nutrients had environmental conditions, which in the case of protein and ash determined these features in more than 80%, and in the case of starch, 70%. With regard to bioactive compounds, the greatest influence of the environment was observed for the amount of TPC (78%), lignin (51%) and the DF complex (56%). The obtained results are useful for breeders working on expanding the pool of common buckwheat genotypes, stable in changing environmental conditions. © 2023 Society of Chemical Industry.


Validation the use of refractometer and mathematic equations to measure dietary formula contents for clinical application.
Gastric residual volumes are widely used to evaluate gastric emptying for patients receiving enteral feeding, but controversy exists about what constitutes gastric residual volume. We have developed a method by using refractometer and derived mathematical equations to calculate the formula concentration, total residual volume (TRV), and formula volume. In this study, we like to validate these mathematical equations before they can be implemented for clinical patient care. Four dietary formulas were evaluated in two consecutive validation experiments. Firstly, dietary formula volume of 50, 100, 200, and 400 ml were diluted with 50 ml water, and then the Brix value (BV) was measured by the refractometer. Secondly, 50 ml of water, then 100 ml of dietary formula were infused into a beaker, and followed by the BV measurement. After this, 50 ml of water was infused and followed by the second BV measurement. The entire procedure of infusing of dietary formula (100 ml) and waster (50 ml) was repeated twice and followed by the BV measurement. The formula contents (formula concentration, TRV, and formula volume) were calculated by mathematical equations. The calculated formula concentrations, TRVs, and formula volumes measured from mathematic equations were strongly close to the true values in the first and second validation experiments (R2>0.98, P<0.001). Refractometer and the derived mathematical equations may be used to accurately measure the formula concentration, TRV, and formula volume and served as a tool to monitor gastric emptying for patients receiving enteral feeding.


Employing Mobile Learning in Music Education.
This study sought to evaluate the effectiveness of introducing digital software in music education to improve academic performance and solfeggio class attendance. To assess academic performance, a test consisting of 25 theoretical questions and 25 practical tasks was developed. The Bologna model was used as an assessment system. The groups were compared by calculating the Student's t-test in terms of the "Test Score" and "Missed Classes" parameters. The collected data revealed that the mean score for the experimental group was 87.50 out of 100, while in the control group, it was much lower, namely 65.37. Likewise, the control group was characterized by satisfactory (D) performance in mastering solfeggio, with the mean score ranging between 64 and 73, whereas experimental group participants had an average of 82-89. The statistical data processing results showed that the six-month use of the ChordIQ app contributed to more effective mastering of solfeggio by amateur musicians. At the same time, the difference between the groups turned out to be significant in both cases, so the research hypothesis was confirmed for both of them (p < 0.05). Overall, the results showed that ChordIQ is a useful mobile app teaching the user music in an exciting and interactive way. The findings collected can be used to update traditional solfeggio curricula, conduct scientific studies in the field of interactive music education, as well as create new dedicated software.


Transfer and transport of aluminum in filtration unit.
Aluminum salt coagulants were used prevalently in various water works. In this article, the effects of filtration on residual aluminum concentration and species distribution were researched by determining the concentration of different aluminum species before and after single layer filter, double layer filter, and membrane filtration units. In the research, size exclusion chromatography (SEC) was used to separate colloidal and soluble aluminum, ion exchange chromatography (IEC) was used to separate organic and inorganic aluminum, and inductivity coupled plasma-atomic emission spectrometry (ICP-AES) was used to determine the aluminum concentration. The results showed that the rapid filtration process had the ability of removing residual aluminum from coagulant effluent water, and that double layer filtration was more effective in residual aluminum removal than single layer filtration, while nano filtration was more effective than micro filtration. It was found that when the residual aluminum concentration was below 1 mg/L in sediment effluent, the residual aluminum concentration in treated water was above 0.2 mg/L. The direct rapid filtration process mainly removed the suspended aluminum. The removal of soluble and colloidal aluminum was always less than 10% and the natural small particles that adsorbed the amount of soluble or small particles aluminum on their surface were difficult to be removed in this process. Micro filtration and nano filtration were good technologies for removing aluminum; the residual aluminum concentration in the effluent was less than 0.05 mg/L.


Nanomaterials 2021 Best Paper Awards: Announcement and Interview with the Winner.
After an extensive voting period, we are proud to present the Best Paper Award to "Carbon Dots and Graphene Quantum Dots in Electrochemical Biosensing [...].


Modern Gamma Knife radiosurgery for management of psychiatric disorders.
Psychiatric disorders result in great suffering of affected patients, who often have rather limited treatment options. In cases refractory to standard medical and behavioral therapy, interventional procedures may be the only feasible solution. The authors experience with Gamma Knife bilateral cingulotomy for treatment-resistant major depression disorder (5 cases) and anorexia nervosa (6 cases), and bilateral anterior capsulotomy for severe obsessive-compulsive disorder (10 cases) shows that such radiosurgical techniques may be applied both effectively and safely. During post-treatment follow-up, the vast majority of patients demonstrated gradual reduction of psychiatric symptoms and improvement of the quality of life, which was confirmed by results of regular neuropsychological testing and imaging examinations. No major side effect was observed in any case. More active application of radiosurgery (using standardized technique) for management of mental illnesses in various Gamma Knife centers worldwide should be encouraged.


Exploratory study on the influence of climatological parameters on Mycoplasma hyopneumoniae infection dynamics.
The objective of the present work was to elucidate the potential relationship between Mycoplasma hyopneumoniae infection and seroconversion dynamics and climatological conditions in four groups of pigs from the same farm born in different seasons of the year. Nasal swabs and blood samples were taken from 184 pigs at 1, 3, 6, 9, 12, 15, 18, 22 and 25 (slaughter age) weeks of age. Outside climatologic parameters, including temperature (°C), relative humidity (%), precipitation (l/m(2)) and wind speed (m/s) were recorded weekly from January 2003 to June 2004. Percentage of nPCR detection of M. hyopneumoniae in nasal swabs was associated significantly with the weekly precipitation rate [P = 0.0018, OR = 1.31 (IC = 1.11-1.55)]; the higher the precipitation rate, the higher the probability of being M. hyopneumoniae nPCR-positive. On the other hand, the percentage of seropositive pigs had a significant association with mean weekly temperature rate [P = 0.0012, OR = 0.89 [IC = 0.84-0.95]); the lower the temperature, the higher the probability of being M. hyopneumoniae seropositive. Animals born in autumn (when higher precipitations rates were recorded), entering finishing units in winter (when lower temperatures were recorded), and reaching slaughter in spring, had the highest probability of being infected by M. hyopneumoniae and the highest probability of being M. hyopneumoniae seropositive.


An impact assessment of the use of aerial logistics to improve access to vaccines in the Western-North Region of Ghana.
Prevention of infectious diseases among children is crucial to improve child health and survival. However, many countries in Sub-Saharan Africa struggle to achieve vaccination targets due to supply chain challenges, which lead to vaccine shortages, stockouts, and increased costs. We evaluated the effects of aerial logistics (centralized storage and delivery by drones) on vaccine stock, stockouts, vaccination coverage and vaccine preventable outcomes in the Western North Region of Ghana. The study combined retrospective quasi-experimental and cross-sectional designs to evaluate supply chain, programmatic, and clinical outcomes. Surveys to health providers were used to collect information from a random sample of 156 facilities, and secondary data on vaccination coverage and clinical outcomes was analyzed at the district level for the years 2017-2021. Facilities served by aerial logistics reported significant reductions in the duration of vaccine stockouts (30 %, p-value < 0.05), as well as in the frequency of missed opportunities for vaccination (44 %, p-value < 0.05). Being served by aerial logistics was associated with increased satisfaction with access to vaccines. Significant differences in vaccination coverage were found for most vaccines, in a range between 13.1 and 37.5 percentage points in vaccination coverage for served districts. Infectious diarrhea cases in children between 5 and 9 years old were reduced by 41.6 % (p-value < 0.05). End-to-end aerial logistics appears as an effective tool to improve the performance of the supply chain for vaccines. The strategy potentially increases the resilience of the health system and contributes to increased vaccination coverage and higher levels of satisfaction among providers in the Western North Region of Ghana.


Cytochrome c peroxidase. Interconversion of chemically and enzymatically reactive and unreactive forms of the ferric protein.
Ferric yeast cytochrome c peroxidase in the presence of different anions may assume a number of forms which differ in optical spectra and chemical properties. In solutions whose only anion is acetate, two spectral forms are present together in an equilibrium. Each of these spectral species is believed to bear bound acetate anion. A form characterized by an intense absorption maximum at 620 nm is unreactive enzymatically and does not react with hydrogen peroxide or with dithionite. A form characterized by a less intense absorption near 645 nm is enzymatically and chemically reactive. Increasing temperature and increasing pH displace the equilibrium toward the 645 nm form. Increasing cytochrome c peroxidase concentration favors the 620 nm form. In kinetic experiments in which the 645 nm form is removed by rapid reaction with H2O2 or dithionite, the 620 nm form is converted in a first order reaction (k = 0.36 s-1, 15 degrees C) to the 645 nm form. In solutions whose sole anion is phosphate a 645 nm form is the only demonstrable spectral species. The enzymatic activity and rates of chemical reaction of 645 nm spectral forms occurring in acetate and in phosphate buffers are the same.


Surface attachment of Listeria monocytogenes is induced by sublethal concentrations of alcohol at low temperatures.
Sublethal concentrations of ethanol or isopropanol increased attachment of Listeria monocytogenes at 10, 20, or 30 degrees C; no induction occurred at 37 degrees C. The alcohol induction phenotype was retained in sigB and cesRK mutants; however, the degree of induction was affected. These results suggest that alcohol may contribute to the persistence of L. monocytogenes.


The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25.
Partial cDNAs of the human TYRO3 gene, encoding a putative receptor tyrosine kinase, and its processed pseudogene (TYRO3P) were cloned from human teratocarcinoma cell, bone marrow and melanocyte cDNA libraries. The tyrosine kinase homologous domains of TYRO3 and TYRO3P were sequenced and compared with each other and with the mouse TYRO3 gene. Abundant levels of the 4.2-kb TYRO3 mRNA were detected in human brain, and lower levels in other human tissues. TYRO3 and TYRO3P were both assigned to human chromosome 15q14-q25 by analysis of DNAs from somatic cell hybrids.


[Microphonic cochlear potentials in the cat during exposure to 2-tons harmonic signals with different phase spectra].
Cochlear microphonic potentials (CM), i. e. the round window responses, evoked by the two-tone sound complexes consisting of the 1st and 2nd harmonics with different phase relation between the components were studied in cats. The spectral analysis of the CM responses showed high sensitivity of the CM potentials to phase changes in the complex sound stimuli. The 1st harmonic in the range of 350--750 Hz could be reduced at a certain phase shift of the 2nd harmonic in the complex signal. The phase and frequency limits of this phenomenon are described.


Synthesis of 1-Aminoisoquinolines and Their Application in a Host-Guest Doped Strategy To Construct Ultralong Room-Temperature Phosphorescence Materials for Bioimaging.
Organic ultralong room-temperature phosphorescence (RTP) materials have attracted great attention for their wide applications in optoelectronic devices and bioimaging. However, the development of these materials remains a challenging task, partially due to the lack of rational molecular design strategies and unclear luminescence mechanisms. Herein, we present a method for facile access to structurally diverse substituted 1-aminoisoquinoline derivatives through a copper-catalyzed one-pot three-component coupling reaction that provides a promising approach to rapidly assemble a library of 1-aminoisoquinolines for exploring the regularity of the host-guest doped system. A series of host-guest RTP materials with wide-ranging lifetimes from 4.4 to 299.3 ms were constructed by doping various substituted isoquinolines derivatives into benzophenone (BP). Furthermore, 4 r/BP nanoparticles could be used for in-vivo imaging with a signal-to-noise ratio value as high as 32, revealing the potential of the isoquinoline framework for the construction of high-performance RTP materials.


Randomized controlled study on the effectiveness of animal-assisted therapy on depression, anxiety, and illness perception in institutionalized elderly.
The aim of this study was to verify dog-assisted therapy's effectiveness on depression and anxiety in institutionalized elderly. Patients' illness perception was examined to identify core beliefs regarding mood, personal control, and illness coherence because they can affect treatment compliance. Subjective perception of pain, social interaction, and setting-bound observable variables were also studied. This study involved a randomized sample of institutionalized patients 65 years of age and older; the treatment group had 17 subjects and the control group had 14 subjects. All patients were administered the Mini-Mental State Examination, 15-item Geriatric Depression Scale, Positive and Negative Affect Schedule, Generalized Anxiety Disorder 7, Illness Perception Questionnaire, and Numeric Pain Rating Scale. Intra- and inter-group data analysis was performed before and after treatment. Over the course of 10 weeks, patients participated in individual 30-min sessions. An observational methodology was developed to record verbal and non-verbal interactions between the elderly, the dog, and the dog handler. A large effect size and a statistically significant decrease in 15-item Geriatric Depression Scale scores were identified in the treatment group. No significant differences were detected in the Generalized Anxiety Disorder 7, Positive and Negative Affect Schedule, and Numeric Pain Rating Scale. However, the Positive and Negative Affect Schedule and the Numeric Pain Rating Scale showed a moderate decrease. The Illness Perception Questionnaire's timeline (acute/chronic) and treatment control subscales showed a clinically relevant, large effect size. Dog-assisted therapy has proved to be effective in reducing symptoms of depression in institutionalized elderly. The increase in verbal interactions with the handlers throughout the study suggests the dog acts as a facilitator of social interaction, eliciting positive emotional responses. Dog-assisted therapy shows promising results in the perception of illness timeline and treatment control, indicating potential enhancement of the sense of treatment-related empowerment. However, further study is required.


Sleep and stressor exposure in relation to circadian rhythms in catecholamine excretion.
12 healthy male volunteers spent 64 h of continuous waking under strictly controlled environmental conditions (light, food, drink, activity) in isolation from the external world. Before and after the vigil the subjects slept in the laboratory. An additional group of five participated only during day time and spent the intervening night period asleep at home. Measurements were carried out in 3 h intervals except for sleep periods. Shortly before the circadian trough and peak of adrenaline excretion respectively, the subjects were exposed to a performance stressor. Results from the vigil showed a very pronounced circadian rhythm for adrenaline excretion but none for noradrenaline excretion. For adrenaline, night-time sleep reduced excretion levels, causing an even more pronounced circadian pattern. For noradrenaline, night-time sleep caused a drop in excretion giving the impression of a circadian rhythm. These and previous results led to the conclusion that the excretion of adrenaline exhibits a self-sustained rhythm while a rhythm in noradrenaline excretion is found only when caused by external synchronizers such as sleep-wake alternation. No difference in magnitude of stress response between peak and trough was observed for any of the catecholamines. Night-time (trough) exposure completely obliterated the circadian rhythm of adrenaline excretion for the duration of the exposure. It was concluded that the normal pronounced night-time trough of adrenaline cannot be due to unavailability of adrenaline in the medulla. With respect to sleep deprivation, no effect was found on excretion levels during waking, during sleep, or in response to the stressor as deprivation progressed. Finally, there was also found to be a close temporal covariation between adrenaline excretion and both rectal temperature and self-rated fatigue (neg.).


Efficacy and safety of botulinum toxin a injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure: a prospective randomized study.
To evaluate the efficacy and safety of botulinum toxin A injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure (CAF). Fifty outpatients with CAF were randomized to receive either a single botulinum toxin injection (30 IU Botox) or topical nitroglycerin ointment 0.2% b.i.d. for 2 wk. If the initial therapy failed, patients were assigned to the other treatment group for a further 2 wk. If CAF still showed no healing at wk 4, patients received combination therapy of botulinum toxin and nitroglycerin for 4 additional wk. Persisting CAF at wk 8 was treated according to the investigator's decision. Healing rates, symptoms, and side effects of the therapy were recorded at wk 2, 4, 8, 12, and 24 after randomization. The group initially treated with nitroglycerin showed a higher healing rate of CAF (13 of 25, 52%) as compared with the botulinum toxin group (6 of 25, 24%) after the first 2 wk of therapy (p < 0.05). At the end of wk 4, CAF healed in three additional patients, all receiving nitroglycerin after initial botulinum toxin injection. Mild side effects occurred in 13 of 50 (26%) patients, all except one were on nitroglycerin. Nitroglycerin ointment was superior to the more expensive and invasive botulinum toxin injection for initial healing of CAF, but was associated with more but mild side effects.


The ruptured PIP breast implant.
Public concern erupted about the safety of Poly Implant Prothèse (PIP) breast implants when it was revealed in 2011 that they contained an inferior, unlicensed industrial-grade silicone associated with a high rate of rupture. There followed national guidance for UK clinicians, which led to a considerable increase in referrals of asymptomatic women for breast implant assessment. In this review we discuss possible approaches to screening the PIP cohort and the salient characteristics of a ruptured implant.


[Genetic structure of an isolated group of the native population of northern Sibiria, the Nganasani (Tavgi) of the Taimyr. III. A family analysis of blood groups].
Family analysis of ABO, MNSs, Rhesus, Duffy and Kell (Kp) in 50 families of nganasans is carried out. Segregation deviations are found in those families where the variation among the children is the widest. The proportion of children from unmarried persons is found to be very small, which supports the existence of traditional monogamic breeding structure in nganasans.


Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement.
Allogeneic hematopoietic stem cell transplantation is the only curative option for a variety of diseases. Despite advances, it is associated with considerable morbidity and mortality, often involving liver complications. Liver disease can be characterized using ultrasound-based liver stiffness measurement. To assess its prognostic value, consecutive patients undergoing allogeneic hematopoietic stem cell transplantation were prospectively evaluated in a single-center study. Endpoints included liver event-free survival and all-cause mortality at 1 year. Competing risk and Cox-regression were used for analysis. We evaluated 106 patients (42 female, age 57) and observed 33 life-threatening events (14 died) including 16 liver complications at 100 days. At 1 year, 36 patients had died, 20 with disease relapse. The hazard ratios for liver-related complications at 100 days were 3.2 (95% CI: 1.8-14.6, p = 0.0022) and 4.4 (95% CI: 1.6-11.9, p = 0.0042) for elevated transient elastography (n = 11) and shear-wave velocity (n = 31), respectively. Results were analogous for all-cause mortality at 1 year. Prior stem cell therapy and elevated gamma glutamyltransferase were also associated with outcome. This demonstrates that elastography is a promising and viable tool for risk prediction and should be included in upcoming multi-center trials to establish new means of guiding treatment and prophylaxis.


Treatment of pompholyx due to nickel allergy with chelating agents.
Ingestion of nickel is important for the chronicity of hand eczema in nickel-sensitive patients. We have tried the effect of chelating agents. Diethyldithiocarbamate (DDC) and tetraethyl thiuramdisulfide (TETD) have proved effective in the treatment of nickel carbonyl poisoning. A 66-year-old woman suffering from severe nickel dermatitis has been treated in three periods, first with DDC 100 mg Q. I. D. for 20 days, and later with TETD 100 mg T. I. D. for two periods. An improvement has been observed in all three experiments.


Objective measurements of nasal airway testing.
The objective measurement of nasal airway function has become increasingly important in the evaluation of both clinical responses and nasal challenge testing methodology when both the diagnosis and treatment of upper respiratory tract disease are assessed. Such measurements include the quantitation of nasal symptoms by use of symptom diaries, nasal physical examination, and scoring systems, and assessment of structural and functional changes of the nasal mucosa by light and electron microscopy and by other methods using radioisotopes. In addition, quantitation of nasal secretions along with qualitative analysis of various components of nasal secretions has recently shed new light on the pathologic picture of nasal disease. Various means of measuring changes in nasal blood flow and nasal airflow have enjoyed increasing use in both investigative and clinical application. Measurement of nasal cross-sectional area along with objective assessment of eustachian tube dysfunction and the use of various pharmacologic and immunologic probes have allowed varying approaches to the evaluation of nasal airway structure and function in both health and disease.


Transcriptional and Epigenetic Control of Regulatory T Cell Development.
The control of immune responses against self and nonharmful environmental antigens is of critical importance to the immune homeostasis. Regulatory T (Treg) cells are the key players of such immune regulation and their deficiency and dysfunction are associated with various immune disorders, such as autoimmunity and allergy. It is therefore essential to understand the molecular mechanisms that make up Treg cell characteristics; that is, how their unique gene expression profile is regulated at transcriptional and epigenetic levels. In this chapter, we focus on the components of molecular features of Treg cells and discuss how they are introduced during their development.


Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys.
Alterations of striatal glutamate receptors are believed to be responsible, at least in part, for the pathogenesis of L-dopa-induced dyskinesias (LID). To evaluate whether co-administration of CI-1041, a novel NMDA receptor antagonist selective for the NR1A/NR2B subtype, with L-dopa might prevent the appearance of this side effect, eight de novo parkinsonian monkeys were treated chronically orally with either L-dopa alone or L-dopa plus CI-1041 (n= 4 for each group). After 4 weeks of treatment with L-dopa alone, all four animals developed moderate dyskinesias either choreic or dystonic in nature. CI-1041 co-treatment completely prevented the induction of dyskinesias in three animals and only one monkey developed mild dyskinesias at the end of the fourth week of treatment in the L-dopa + CI-1041 group. The magnitude and duration of the antiparkinsonian action of L-dopa was similar in both groups. These results suggest that selective NMDA receptor antagonism may be interesting for managing LID in Parkinson's disease patients.


[AUDITORY OUTCOMES OF COCHLEAR IMPLANTATION IN MENIERE'S DISEASE].
Cochlear implants are valuable in the auditory rehabilitation of patients with severe to profound hearing loss. However, there is limited data on the outcomes of cochlear implantation in patients with Meniere's disease (MD). In this study, we aim to evaluate the auditory outcomes of cochlear implantation in patients with MD. A retrospective case series of patients with MD and severe to profound sensorineural hearing loss (SNHL), who underwent cochlear implantation at a tertiary academic center between 2006-2017. Patient's clinical characteristics and audiometric data were reviewed. The study included 20 ears in 19 patients with MD who underwent cochlear implantation with available pre- and postoperative audiometric data. There were 10 males and 9 females with a mean age of 63 years and a mean follow-up duration of 70.8 months. Pre- and post-implant CNC word recognition scores were 18.31% and 66.89%, respectively (p<0.001). Pre- and post-implant AzBio and/or HINT sentence recognition scores were 12.25% and 68.28% in quiet, respectively (p<0.001), and 18.25% and 63.43% in noise, respectively (p<0.001). Cochlear implantation resulted in an improvement of word and sentence recognition scores in MD patients. These results support the role of cochlear implants in the auditory rehabilitation of MD. Dr. Samy received research support from Cochlear Corporation.


Agreements and uncertainties in autologous haematopoietic stem cell mobilization and collection. A Spanish consensus document.
Although many experts position statements on autologous stem cell mobilization have been published, there are some aspects that are still under discussion. A Spanish Hematologist expert group was summoned to settle on agreements and uncertainties on PBSCs mobilization, including factors not always considered; as apheresis and cytometry key factors that determine a successful PBSC collection. This document reviews critical factors that define poor mobilizer patients and the tools to better collect the desired stem cells for a successful autologous haematopoietic stem cell transplant.


Analysis of Fear Post COVID in First-Year Students after the Incorporation to the Classroom: Descriptive Study in University Students of Health Sciences.
After the onset of the COVID-19 pandemic, social restriction measures were implemented, among them, the adaptation of university teaching to online modality until the end of the 2019-2020 school year in order to stop the spread of the SARS-CoV-2 virus. At the beginning of the 2020-2021 school year, the Spanish universities opted for face-to-face teaching. To that end, different special measures and adaptations were implemented in higher education facilities, aimed at minimizing the risk of infection and ensuring safe face-to-face learning. The objective was to explore and describe the level of fear of first-year students after the start of in-person classes in the context of the COVID-19 pandemic. The sample was 185 first-year students who were evaluated on the first day of class. For that purpose, an ad-hoc questionnaire was administered to collect demographic information and to find the level of fear and concern. The Fear of COVID-19 Scale was used to assess the severity of the participants' fear of the pandemic situation. The results indicate that participating university population does not report fear of the virus, but they describe various psychosomatic characteristics, such as increased pulse rate and heart palpitations (p = 0.008) and insomnia (p = 0.05) when they think about infection with coronavirus. Nevertheless, when data are disaggregated by gender, we observe differences specifically in women (83.2%), such as fear (p = 0.006) and sweaty hands when they think of the virus (p = 0.023). Incoming university freshmen do not express concern or fear of potential infection with COVID-19, but they are concerned about family transmission after beginning face-to-face classes.


Pain complaints in a sample of psychiatric inpatients.
We examined the prevalence of pain and pain severity in a sample of psychiatric inpatients. Currently, scant information exists about which patient groups are most affected by pain. Pain was assessed in 416 psychiatric inpatients using the brief pain inventory. Patients were characterized by applying DSM-IV criteria and obtaining self-reports of adverse childhood experiences. Of psychiatric inpatients, 31.0% reported having substantial pain. Women with posttraumatic stress disorder (PTSD) had the highest prevalence of substantial pain among all psychiatric inpatients and a significantly higher rate compared to women without PTSD (49% vs. 28%, P=.02). Pain was significantly associated with adverse childhood experiences in both men and women. Within a group of psychiatric inpatients, pain is associated with PTSD in women and with adverse childhood experiences in both men and women. Attention should therefore be paid towards such high-risk groups and the consequences that the pain might entail for physical and mental health.


[Chediak-Higashi syndrome].
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, high bleeding tendency, and various neurological symptoms. Onset in early childhood mostly leads to lymphohistiocytic infiltration into multiple organs, which is usually lethal without bone marrow transplantation. The adult form of CHS has a milder course, no lymphohistiocytic infiltration, and is characterized by neurological manifestations such as polyneuropathy, parkinsonism, dementia, and ataxia. In young adults, a combination of these defects with oculocutaneous albinism or recurrent infections should bring CHS into consideration. Diagnosis is established by the presence of characteristic eosinophilic peroxidase-positive giant granules in leukocytes. This article summarizes current knowledge about the pathogenesis, clinical course, and therapy of CHS and reports on experience with two adult CHS patients.


Modulation of cellular metabolism by protein crotonylation regulates pancreatic cancer progression.
Protein lysine crotonylation has been recently identified as a vital posttranslational modification in cellular processes, particularly through the modification of histones. We show that lysine crotonylation is an important modification of the cytoplastic and mitochondria proteins. Enzymes in glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, glutamine metabolism, glutathione metabolism, the urea cycle, one-carbon metabolism, and mitochondrial fusion/fission dynamics are found to be extensively crotonylated in pancreatic cancer cells. This modulation is mainly controlled by a pair of crotonylation writers and erasers including CBP/p300, HDAC1, and HDAC3. The dynamic crotonylation of metabolic enzymes is involved in metabolism regulation, which is linked with tumor progression. Interestingly, the activation of MTHFD1 by decrotonylation at Lys354 and Lys553 promotes the development of pancreatic cancer by increasing resistance to ferroptosis. Our study suggests that crotonylation represents a metabolic regulatory mechanism in pancreatic cancer progression.


The emergence of phosphate as a specific signaling molecule in bone and other cell types in mammals.
Although considerable advances in our understanding of the mechanisms of phosphate homeostasis and skeleton mineralization have recently been made, little is known about the initial events involving the detection of changes in the phosphate serum concentrations and the subsequent downstream regulation cascade. Recent data has strengthened a long-established hypothesis that a phosphate-sensing mechanism may be present in various organs. Such a phosphate sensor would detect changes in serum or local phosphate concentration and would inform the body, the local environment, or the individual cell. This suggests that phosphate in itself could represent a signal regulating multiple factors necessary for diverse biological processes such as bone or vascular calcification. This review summarizes findings supporting the possibility that phosphate represents a signaling molecule, particularly in bone and cartilage, but also in other tissues. The involvement of various signaling pathways (ERK1/2), transcription factors (Fra-1, Runx2) and phosphate transporters (PiT1, PiT2) is discussed.


IRF5 and IRF8 modulate the CAL-1 human plasmacytoid dendritic cell line response following TLR9 ligation.
Synthetic oligonucleotides (ODNs) containing CpG motifs stimulate human plasmacytoid dendritic cells (pDCs) to produce type-1 interferons (IFNs) and proinflammatory cytokines. Previous studies demonstrated that interferon regulatory factors (IRFs) play a central role in mediating CpG-induced pDC activation. This work explores the inverse effects of IRF5 and IRF8 (also known as IFN consensus sequence-binding protein) on CpG-dependent gene expression in the human CAL-1 pDC cell line. This cell line shares many of the phenotypic and functional properties of freshly isolated human pDCs. Results from RNA interference and microarray studies indicate that IRF5 upregulates TLR9-driven gene expression whereas IRF8 downregulates the same genes. Several findings support the conclusion that IRF8 inhibits TLR9-dependent gene expression by directly blocking the activity of IRF5. First, the inhibitory activity of IRF8 is only observed when IRF5 is present. Second, proximity ligation analysis shows that IRF8 and IRF5 colocalize within the cytoplasm of resting human pDCs and cotranslocate to the nucleus after CpG stimulation. Taken together, these findings suggest that IRF5 and IRF8, two transcription factors with opposing functions, control TLR9 signaling in human pDCs.


IFN-γ production downstream of NKT cell activation in mice infected with influenza virus enhances the cytolytic activities of both NK cells and viral antigen-specific CD8+ T cells.
Natural killer T (NKT) cell activation is responsible for eliminating pathogens. However, the biological functions of NKT cells against influenza virus are not fully understood. We therefore investigated the effects of NKT cells in viral infection using CD1d knockout (KO) mice. When CD1d KO or wild-type (WT) mice were infected with a sub-lethal dosage of the influenza virus, the survival rate of CD1d KO mice was significantly lower than for WT mice in association with delayed viral clearance in the lungs. Consistently, IFN-γ production in bronchoalveolar lavage fluid of CD1d KO mice was largely reduced compared to WT mice during infection. Moreover, the cytotoxic activities of NK cells and viral antigen-specific CD8(+) T cells were impaired in CD1d KO mice. It was concluded that activated NKT cell-induced IFN-γ release enhances both NK-cell activity and antigen-specific CD8(+) T cells to eliminate the influenza virus, thus leading to an enhanced survival.


Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells.
Previously, it has been demonstrated that HIF-1α has close connection with malignant tumor progression, aggressive behavior and prognosis. In addition, proton pump inhibitors (PPIs) have been reported to selectively induce tumor cell apoptosis, thus exerting its anticancer effects. In vitro and in vivo our study revealed that pantoprazole (PPZ) inhibited tumor cells proliferation, induced apoptosis and decreased the expression of HIF-1α protein. In summary, PPZ could suppress tumor growth acting as a HIF-1α protein inhibitor.


Epidemiology of Tuberculosis in the United States.
Although considerable progress has been made in reducing US tuberculosis incidence, the goal of eliminating the disease from the United States remains elusive. A continued focus on preventing new tuberculosis infections while also identifying and treating persons with existing tuberculosis infection is needed. Continued vigilance to ensure ongoing control of tuberculosis transmission remains key.


Rage attacks in children and adolescents with Tourette's disorder: a pilot study.
Sudden, explosive episodes of rage occur in a significant number of clinically referred children with Tourette's disorder and cause considerable psychosocial morbidity. The etiology of these symptoms is unknown. We conducted a pilot study of 12 consecutive children with Tourette's disorder and rage attacks to determine whether comorbidity of Tourette's-associated disorders is related to these symptoms. Twelve consecutive children with Tourette's disorder who presented with rage attacks were evaluated, including 2 females and 10 males. Tourette's disorder diagnosis, presence of comorbid disorders, and tic severity were assessed using DSM-IV diagnostic criteria and standardized rating scales. All 12 children met diagnostic criteria for Tourette's disorder, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). Two children were also diagnosed with comorbid oppositional defiant disorder, and 4 children were diagnosed with comorbid conduct disorder. None of the subjects met diagnostic criteria for a mood disorder. All subjects had only mild tic severity. The clinical phenomenon of rage attacks in children with Tourette's disorder resembles intermittent explosive disorder and may reflect specific underlying neurologic disturbances. This pilot study suggests that rage attacks in Tourette's disorder may be related to the presence of comorbid disorders.


Therapeutic effects of interleukin-37 and induced cardiosphere on treating myocardial ischemia-reperfusion injury.
Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. In the current study, we investigated the therapeutic advantages of delivering Interleukin-37 (IL-37) by induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, in treating the mice model MI-RI. The mouse model of MI-RI was established and the iCS cells with IL-37 overexpression (iCS-IL37) were transplanted into the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography and hemodynamic assessment. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA). The LV function was significantly improved after the iCS-IL37 transplantation when compared to the vehicle control group and iCS group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS-IL37 transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were down-regulated by the iCS-IL37 transplantation. The present study indicated that the iCS with IL-37 overexpression had therapeutic effects on the mice model of MI-RI.


Evaluation of multidimensional (ion-exchange/reversed-phase) protein separations using linear and step gradients in the first dimension.
The performance characteristics of multidimensional liquid chromatographic protein separations were evaluated using on-line electrospray mass detection, and a novel workflow for automated LC/MS data processing. Two-dimensional ion exchange/reversed-phase LC separations of Escherichia coli cytosol were conducted using either a continuous linear or discontinuous step gradient in the first dimension. Chromatographic profiles of the top 100 most abundant components were characterized to assess overall separation reproducibility within each mode, and to characterize differences in component distribution between the two modes of operation. Analysis of the resulting data indicates that multidimensional separations of complex protein mixtures can be done reproducibly. Furthermore, under the conditions employed within this study, a linear first dimension gradient was more effective at fractionating the protein mixture, distributing fewer major components to multiple second dimension cycles than an equivalent step gradient. The application of on line mass spectrometry, and automated processing of the resulting data, proved valuable for producing component level analysis of multidimensional protein separations.


The prevalence of systemic sclerosis is increased among patients with alopecia areata: a population-based study.
Although the coexistence of alopecia areata (AA) and systemic sclerosis (SSc) has been anecdotally reported, the association between these conditions has been poorly investigated. We aimed to assess the association between AA and SSc using a large-scale real-life computerized database. A cross-sectional study was conducted comparing the prevalence of SSc among patients with AA and among age-, sex-, and ethnicity-matched control subjects. Chi-square and t tests were used for univariate analysis, and logistic regression model was used for multivariate analysis. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4.4 million subjects. A total of 51,561 patients with AA and 51,410 controls were included in the study. The prevalence of SSc was increased in patients with AA as compared with the control group (0.1% vs. 0.0%, respectively; OR, 2.30; 95% CI, 1.2-4.4; P = 0.010). The association was stronger among older and Jewish patients. In a multivariate analysis adjusting for sex, age, ethnicity, and other comorbidities, AA was still independently associated with SSc (OR, 2.3; 95% CI, 1.2-4.4; P = 0.012). In conclusion, a significant positive association was revealed between AA and SSc. Further studies are necessary to establish these findings in other study populations and to elucidate the mechanism underlying this association. Awareness of SSc may be of importance for physicians treating patients with AA, and screening for SSc in patients with relevant symptoms may be considered.


Arrhythmia prophylaxis after coronary artery surgery. A randomised controlled trial of intravenous magnesium chloride.
One hundred and thirty patients undergoing elective myocardial revascularisation were randomised to receive an intravenous infusion containing either 50 mmol magnesium chloride or placebo during the first 48 h following surgery. Magnesium was given to 66 patients and a placebo infusion to 64 patients. Postoperative serum magnesium concentrations fell in the placebo group (from 0.83 +/- 0.06 to 0.79 +/- 0.11 mmol/l) but were elevated in the magnesium group (from 0.82 +/- 0.05 to 1.2 +/- 0.25 mmol/l). In total, 35 patients (26.9%) had a supraventricular arrhythmia, of which 11 were in the magnesium group (16.7%) and 24 (37.5%) in the placebo group (P = 0.013). Three patients in the magnesium group had an episode of ventricular fibrillation and three patients in the placebo group had frequent ventricular ectopics. There was one death in the magnesium group associated with a perioperative myocardial infarction. This study shows that intravenous magnesium supplements reduce the incidence of supraventricular arrhythmias following coronary artery surgery.


More stereotypes, please! The limits of 'theory of mind' and the need for further studies on the complexity of real world social interactions.
I suggest that the Stereotype Rationality Hypothesis (Jussim 2012) is only partially right. I agree it is rational to rely on stereotypes, but in the complexity of real world social interactions, most of our individuating information invokes additional stereotypes. Despite assumptions to the contrary, there is reason to think theory of mind is not accurate, and social psychology's denial of stereotype accuracy led us toward mindreading/theory of mind - a less accurate account of how we understand other people.


Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal.
Fezolinetant is a neurokinin 3 receptor antagonist under investigation for treatment of menopausal symptoms. In a recent study, Lederman and colleagues1 reported the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.


[Distal and late ureteral obstruction: a rare complication following dextranomer/hyaluronic acid injection for vesicoureteral reflux in children].
Surgically relevant obstruction after dextranomer/hyaluronic acid injection (Dx/Ha, Deflux(®)) for the treatment of vesicoureteral reflux (VUR) is rare with a 0.6% incidence. It occurs usually during the early postoperative period. We report here the case of a 9-year-old boy with a history of VUR who was previously treated with Deflux(®) and was referred more than 2 years later with acute flank pain (as he already did 2 weeks after surgery with a spontaneous relief under medical treatment). Initial radiological investigations showed hydronephrosis caused by distal ureteral obstruction which required open surgery removal of the Dx/Ha and Cohen procedure. This is the second case of delayed symptomatic obstruction due to Dx/Ha reported in the literature.


Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models.
This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants' heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.


Chronic Subdural Hematoma: Epidemiology and Natural History.
This article discusses the epidemiology and natural history of chronic subdural hematoma (CSDH), a common disease prevalent in the elderly population. The incidence of CSDH ranges from 1.72 to 20.6 per 100,000 persons per year. Risk factors include advancing age, male gender, and antiplatelet or anticoagulant use. Clinical progression is separated into 3 distinct periods, including the initial traumatic event, the latency period, and the clinical presentation period. The recurrence of CSDH and nonsurgical predictive factors are described in detail to provide a comprehensive understanding of the outcome of this disease.


Randomized double-blind trial of injectable heptaminol for controlling spontaneous or bromocriptine-induced orthostatic hypotension in parkinsonians.
Heptaminol is a molecule with experimental cardiovascular analeptic properties. In this double-blind vs placebo trial, the potency, so far unproven, of the injectable form of a 626 mg dose of heptaminol chlorhydrate on spontaneous or induced orthostatic hypotension (OH), was assessed. Nineteen patients were included in the study: 7 displayed spontaneous OH, and in the other 12 OH was induced by bromocriptine, as monitored 103 min/after an oral intake of 6.6 mg on average. Neither spontaneous nor induced OH were recorded in 32% of the Parkinsonian population registered, with no obvious distinctive characteristics. Potency tilt-trials, performed 15, 30 and 45 min after parenteral administration of heptaminol, revealed a significant and expressive potency of the molecule on the systolic blood pressure after 15 min (P less than 0.05). Clinical and biological tolerance was excellent. Low plasma renin activity and the absence of response to orthostatism indicated, in this population of Parkinsonian extrapyramidal syndromes, a loss in positive tonus likely to be of sympathetic origin. The anti-hypotensive action of heptaminol does not seem to be related to any renal or even sympathetic interaction.


NS-398, a cyclooxygenase-2-specific inhibitor, delays skeletal muscle healing by decreasing regeneration and promoting fibrosis.
Nonsteroidal anti-inflammatory drugs are often prescribed after muscle injury. However, the effect of nonsteroidal anti-inflammatory drugs on muscle healing remains primarily controversial. To further examine the validity of using these drugs after muscle injury, we investigated the working mechanism of NS-398, a cyclooxygenase-2-specific inhibitor. In vitro experiments showed that NS-398 inhibited the proliferation and maturation of differentiated myogenic precursor cells, suggesting a detrimental effect on skeletal muscle healing. Using a mouse laceration model, we analyzed the in vivo effect of NS-398 on skeletal muscle healing at time points up to 4 weeks after injury. The in vivo results revealed delayed muscle regeneration at early time points after injury in the NS-398-treated mice. Compared to controls, lacerated muscles treated with NS-398 expressed higher levels of transforming growth factor-beta1, which corresponded with increased fibrosis. In addition, transforming growth factor-beta1 co-localized with myostatin, a negative regulator of skeletal muscle growth. We also found reduced neutrophil and macrophage infiltration in treated muscles, indicating that the delayed skeletal muscle healing observed after NS-398 treatment could be influenced by the anti-inflammatory effect of NS-398. Our findings suggest that the use of cyclooxygenase-2-specific inhibitors to treat skeletal muscle injuries warrants caution because they may interfere with muscle healing.


Novel synthesized aminosteroidal heterocycles intervention for inhibiting iron-induced oxidative stress.
The objective of this study was to elucidate the potential role of novel synthesized aminosteroidal heterocyclic compounds 2, 5, 9b and 10c against iron-induced oxidative stress with particular insight on erythrocyte ghosts in male rats. Chronic iron supplementation (3000 mg kg(-1) diet) for 6 weeks significantly increased plasma iron and ferritin levels. It also produced significant increase in plasma TNF-alpha and NO levels. Lipid metabolism was also affected by excess iron, so that plasma and erythrocyte membrane total cholesterol, triglycerides, phospholipids and total lipid levels were significantly elevated. In consequence, a significant increase in plasma leptin level was detected. Iron overload clearly induces oxidative stress as indicated by the significant increase in both plasma and erythrocyte membrane lipid peroxidation levels. Noteworthy, excess iron not only decreased the mean value of erythrocyte membrane protein but also caused marked alterations in the membrane protein fractions with concomitant inhibition in erythrocyte membrane ATPases activity. On the other hand, treatment with the aminosteriodal heterocyclic compounds especially compounds 5, 2, and 10c in an oral dose of 5 mg kg(-1) B.W. per day could ameliorate almost all of the changes in plasma and erythrocyte ghosts components induced by iron overload. The efficacious role of these novel synthesized aminosteriods in preventing iron-induced oxidative stress may be mediated through their iron chelating properties, anti-lipid peroxidation activities and membrane stabilizing actions. The encouraging results obtained in the present study lend credence to substantial investigation to assess the use of these compounds as a potent line of therapy to retard the pathogenesis of iron overload diseases.


Postoperative Interventions in Pediatric Digital Replantation: A Tertiary Referral Center Case Review.
Although a few case series have been published describing the excellent outcomes of replantation and revascularization operations in children, there has been limited study of the hospital course that these patients experience and the number of potentially harmful interventions and treatments that occur. The purpose of this study was to detail the results of various postoperative interventions, including anticoagulation, transfusion, leeching, sedation, and additional anesthetic exposures. Twenty-nine patients aged less than 18 years had 34 digital revascularizations or replantations performed between January 2000 and May 2020. The details of each patient's presentation, surgery, and postoperative care were analyzed. Nine of 29 children underwent repeat anesthetics, including 6 revision amputations. No demographic, surgical, or postoperative variables consistently preceded revision amputation or additional anesthetic procedures. Only 5 patients had >1 hemoglobin (Hb) measurement. Two patients received blood transfusions; the average drop in Hb was 3.5 g/dL from before surgery to the lowest after surgery. Four patients underwent leech therapy. Only patients receiving leech therapy required postoperative transfusions. Anticoagulation regimens were prescribed on the basis of demographic and surgical factors, although no medication or regimen seemed to affect outcomes. Although the experience of digital replantation is essentially the same in pediatric patients as adults, there may be different ramifications for children. Specifically, postoperative management of pediatric digital replantation or revascularization can involve multiple interventions that carry their risks. Parents should be counseled about the risks of anticoagulants, transfusions, and repeat anesthetics, and clinicians should monitor Hb closely when using leech therapy. Case series, Therapeutic IV.


Inhibition of coronary circulatory failure and thromboxane A2 release during coronary occlusion and reperfusion by 2-phenylaminoadenosine (CV-1808) in anesthetized dogs.
The effects of potent coronary vasodilator, 2- phenylaminoadenosine (CV-1808), on coronary circulatory failure and thromboxane (TX) A2 release were studied during coronary occlusion (for 60 min) and subsequent reperfusion (for 60 min) in anesthetized dogs. During coronary reperfusion, reactive hyperemic response was attenuated, and coronary conductance decreased gradually with time, suggesting coronary circulatory failure. TXA2 release was markedly increased, as demonstrated by contraction of rabbit aortic strips perfused with coronary venous blood draining the ischemic myocardium, and by increased release of radioimmunologically assayable TXB2. CV-1808 (0.25 microgram/kg/min i.v. infusion throughout the experimental period, starting 10 min before coronary occlusion) inhibited coronary circulatory failure and TXA2 release. TXA2 synthetase of horse platelet microsomes was not significantly inhibited (-11.6 +/- 2.1%) by 10(-4) M CV-1808. The compound (10(-5) and 10(-4) M) inhibited collagen-induced TXB2 formation in a dose-dependent manner (-23.0 +/- 9.0 and -74.0 +/- 15.0%, respectively), but not arachidonic acid-induced TXB2 formation by dog platelets, suggesting that CV-1808 inhibited phospholipases. Myocardial infarct size determined 60 min after reperfusion was significantly reduced by CV-1808. Thus, CV-1808 appeared to be effective for salvaging ischemic myocardium. The effect might be related to improvement of coronary circulation and inhibition of release of vasoactive substances, including TXA2, from the ischemic myocardium.


Validation of four automatic devices for self-measurement of blood pressure according to the International Protocol of the European Society of Hypertension.
Four electronic devices for self-measurement of brachial blood pressure (BP): the Omron M1 Plus, the Omron M6 Comfort, the Spengler KP7500 D, and the Microlife BP A100 Plus, were evaluated in four separate studies according to the International Protocol of the European Society of Hypertension (ESH). The International Validation Protocol is divided into 2 phases: the first phase is performed on 15 selected subjects (45 pairs of BP measurements); if the device passes this phase, 18 supplementary subjects are included (54 pairs of BP measurements) making a total number of 33 subjects (99 pairs of BP measurements) on which the final validation is performed. The same methodology recommended by the ESH protocol was applied for the 4 studies. In each study and for each subject, 4 BP measurements were performed simultaneously by 2 trained observers using mercury sphygmomanometers alternately with 3 measurements by the tested device. The difference between the BP value given by the device and that obtained by the two observers (mean of the two observers) was calculated for each measure. The 99 pairs of BP differences were classified into 3 categories (< or =5, 10, < or =15 mmHg). The number of differences in each category was compared with the number required by the International Protocol. An individual analysis was then done to determine for each subject the number of comparisons < or =5 mmHg. At least 22 of the 33 subjects should have 2 of their 3 comparisons < or =5 mmHg. All 4 tested devices passed the first and the second phase of the validation process. The average differences between the device and mercury sphygmomanometer readings were -1.4 +/- 5.5 and -0.4 +/- 4.8 mmHg for SBP and DBP respectively for the Omron M1 Plus device, -2.1 +/- 7.4 and 0.1 +/- 4.9 mmHg for SBP and DBP respectively for the Omron M6 Comfort device, -1.4 +/- 8.6 and -0.1 +/- 3.5 mmHg for SBP and DBP respectively for the Spengler KP7500 D device, and 1.6 +/- 4.2 mmHg and 0.54 +/- 2.8 mmHg for SBP and DBP respectively for the Microlife BP A100 Plus device. For all devices, readings differing by less than 5, 10, and 15 mmHg for SBP and DBP values fulfill the recommendation criteria of the International Protocol as well as the individual analysis. Omron M1 Plus (HEM-401 1C-E), Omron M6 Comfort (HEM 7000-E), Spengler KP7500 D, and Microlife BP A100 Plus devices fulfilled the validation recommendations of the International Protocol.


Prospective study of perceived stress in cardiac patients.
Psychological stress is known to have a negative effect on the health and well-being of coronary artery disease (CAD) patients. Although the study of stress CAD samples has received considerable attention, few studies have examined the effects of gender and age, had multiple follow-ups over an extended period, and had extensive baseline assessment batteries. In this study, demographic, clinical, social, and personality variables were evaluated as predictors of nine repeated assessments of stress over a 2-year period in 322 CAD patients (33.2% female). At baseline, perceived social support, coping style, and social conflict were associated with stress ratings. Mixed models were used to evaluate predictors of reported stress during the subsequent 2 years. The results showed that higher stress was present in patients who were female and young. Follow-up stress was also found in patients with moderate income, congestive heart failure, high social conflict, low social support, and negative coping style. These findings may help clinicians identify patients who are likely to experience higher levels of stress over a prolonged period following a diagnosis of CAD and may also suggest which patients may benefit most from stress reduction interventions.


The effect of carbon surface chemical composition on the adsorption of acetanilide.
The study of acetanilide adsorption-desorption performed at three temperatures (300, 310, and 320 K) and at two pH levels (7.0 and 1.5) on the series of D43/1 carbons (initial and modified with HNO3, fuming H2SO4, and gaseous NH3) is reported. Sorption data are additionally supplemented with the results of thermal analysis and calorimetric and kinetic measurements. It is shown that, generally, acetanilide adsorption at the neutral pH level is reversible (only on the more acidic carbons and at the lowest temperature does hysteresis occur due to the formation of hydrogen bonds with surface OH groups), and it decreases for the chemically modified carbons. In contrast, at the acidic pH level acetanilide adsorption is irreversible. A mechanism of irreversibility is proposed and it is shown that hysteresis is caused by the chemical reaction between the nucleophile (carbon) and the protonized acetanilide molecules. For all studied carbons, at the acidic pH level, adsorption increases and this is caused by the weakly basic character of acetanilide molecule. Adsorption results are described applying adsorbability and Dubinin-Astakhov, quasi-Freundlich and solution analogue of the Toth adsorption isotherm equations. Using the kinetic data, the effective diffusion coefficients and the energy of diffusion are calculated. It is shown that the diffusion is mainly a surface process, and the contribution of the pore diffusion increases with the rise in temperature. By applying different correlations between the parameters obtained from the theoretical description of experimental data and those characterizing the chemical composition of the studied carbons, the role of the latter in the adsorption and kinetics of acetanilide adsorption is determined.


The Neuropilins and Their Ligands in Hematogenous Metastasis of Salivary Adenoid Cystic Carcinoma-An Immunohistochemical Study.
We investigated the expression of neuropilin-1 (NRP1), neuropilin-2 (NRP2), vascular endothelial growth factor-A (VEGF-A), semaphorin-3A (Sema-3A), and semaphorin-3F (Sema-3F) in normal salivary gland (NSG) tissue, nonmetastatic salivary adenoid cystic carcinoma (SACC), and metastatic SACC to better understand their role in intratumoral angiogenesis and hematogenous metastasis of SACC. The study included 60 SACC patients, equally divided between nonmetastatic SACC and metastatic SACC. We used 30 NSG samples as the control. The expression of cytokines was studied by immunohistochemistry and compared using the integrated optical density. The relationship between NRP1, NRP2, VEGF-A, and Sema-3A expression and microvessel density (MVD) was analyzed in the 3 groups. In metastatic SACC, the expression levels of NRP1 and VEGF-A were significantly greater than those in nonmetastatic SACC and NSG. The expression of Sema-3A and Sema-3F was significantly lower in metastatic SACC than that in nonmetastatic SACC and NSG (P < .0001). No significant differences were found in NRP2 expression among the 3 groups (P = .43). The MVD of metastatic SACC was significantly greater than that of nonmetastatic SACC and NSG (P < .0001). However, the lymphatic vessel density of the 3 groups was not significantly different statistically. The relationship between MVD and NRP1 or VEGF-A showed a significant positive correlation (P < .0001, for both). However, a significant negative correlation was found between the MVD and Sema-3A or Sema-3F expression (P < .0001, for both). Hematogenous metastasis of SACC is correlated with high expression of NRP1 and VEGF-A and low expression of Sema-3A and Sema-3F. The increased numbers of microvessels induced by VEGF-A signaling, combined with NRP1, could be one of the key reasons leading to the enhanced hematogenous metastasis in SACC.


Nanofibrillated chitosan coated highly ordered titania nanotubes array/graphene nanocomposite with improved biological characters.
Designing multifunctional surfaces is key to develop advanced materials for orthopedic applications. In this study, we design a double-layer coating, assembled onto the completely regular titania nanotubes (cRTNT) array. Benefiting from the biological and topological characteristics of chitosan nanofibers (CH) and reduced graphene oxide (RGO) through a unique assembly, the designed material features promoted osteoblast cell viability, prolonged antibiotic release profile, as well as inhibited bacterial biofilm formation. The synergistic effect of RGO and CH on the biological performance of the surface is investigatSed. The unique morphology of the nanofibers leads to the partial coverage of RGO-modified nanotubes, providing an opportunity to access the sublayer properties. Another merit of this coating lies in its morphological similarity to the extracellular matrix (ECM) to boost cellular performance. According to the results of this study, this platform holds promising advantages over the bare and bulk biopolymer-modified TNTs.


Intellectual ability in adolescents with conduct disorder.
A U.K. population of young offenders show the typical deficits in Verbal IQ reported in conduct disordered populations. Performance IQs are generally lower than those of previous studies from the 1970s, raising a question about decline in intellectual ability.


Polymorphisms in the endothelin-1 (EDN1) are associated with asthma in two populations.
Endothelin-1 (EDN1) has been reported to be implicated in the pathophysiology of asthma. Literature results on the genetic association of EDN1 in asthma are inconsistent. Eleven single nucleotide polymorphisms in EDN1 were genotyped in 342 and 100 families from UK and Norway, respectively. Asthma, bronchial hyperreactivity (BHR) and atopic asthma phenotypes were analyzed for the family-based association. Five single nucleotide polymorphisms (SNPs) were associated with asthma (0.0017<or=P<or=0.0291), five with BHR (0.0026<or=P<or=0.0315) and three with atopic asthma (0.0016<or=P<or=0.041) in the UK population. Three SNPs were associated with asthma (0.0041<or=P<or=0.019), seven with BHR (0.0018<or=P<or=0.041) and two with atopic asthma (0.0123<or=P<or=0.0153) in the Norwegian population. A polymorphism (rs1800541) in the promoter region of EDN1 was replicated in the two populations. A nonsynonymous coding polymorphism (rs5370) resulting in a change of amino acid Asn to Lys at position 198 was also replicated. The results of haplotype-based association analyses strongly supported the ones of single SNP associations. This study demonstrates the significant evidence of association between polymorphisms in EDN1 and asthma.


An epidemiological model of rinderpest. I. Description of the model.
The development of an epidemiological model of rinderpest in cattle and wildlife populations is described. The model uses a state-transition structure, incorporating a stochastic element through the use of Monte-Carlo methods modified to allow large populations to be simulated. The potential applications include the estimation of "safe" host population immunity rates and the design of cost-effective rinderpest vaccination programmes.


The prevention of nasal liquorrhea caused by transphenoidal surgery for pituitary adenomas. Technical note.
The Authors report their experience in the surgical treatment of nasal liquorrhea in transphenoidal surgery. They suggest the use of clotting substances like the adhesive Tissucol in order to prevent this complication.


Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex.
Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs) activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh) and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode) and field potential recordings. CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M₁/M₄ mAChRs antagonist) but not by AF-DX 116 (M₂/M₄ mAChRs antagonist). Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP) but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABA(A) and GABA(B) receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M₁/M₄ mAChRs agonist), yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition. These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M₁ mAChR, decrease of inhibition by M₂ mAChR and depression of excitatory transmission by M₄ mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the concomitant depression of inhibition would facilitate long-term potentiation. Thus, this triade of effects may represent a "neuronal correlate" of attention and learning.


Clinical profile and outcome of infantile onset diabetes mellitus in southern India.
To study the etiology, clinical presentation and outcome of infantile onset diabetes mellitus (IODM). Descriptive cohort study. Retrospective study from 1999-2007 and prospective from 2008-2012. The diabetic clinic at a Pediatric tertiary care referral institute in Chennai. All infants diagnosed to have diabetes at less than one year of age were studied. Study variables were age at onset, gender, mode of presentation, birth weight, initial blood glucose, serum HbA1c, serum c peptide levels, outcome at initial presentation, insulin requirement, associated comorbid conditions, genetic analysis and outcome at the end of the study or until they were followed up. 40 infants with infantile onset diabetes were studied, constituting 8% of all children with onset of DM at less than 12 years of age. 67.5% of these children presented with diabetic keto acidosis (DKA), only 30% had a provisional diagnosis of DM or DKA at first physician contact. 63% of IODM with onset less than 6 months and 30% with onset more than 6 months were of low birth weight. Nearly 85% of the study group had low C-peptide levels. 84.5% of IODM with onset less than 6 months and 55% of those with onset more than 6 months were monogenic. Wolcott Rallison syndrome was the commonest type encountered. Genetic diagnosis aided switching over from insulin to oral sulphonylurea in 5 children with KCNJ11 and ABCC8 mutations. Missed diagnosis, recurrent admissions for metabolic instability and developmental delay were common problems in IODM. Mortality at 12.5 year follow up was 32.5%. IODM with onset at less than 6 months is predominantly monogenic and low birth weight is more common. 55% of IODM were misdiagnosed at onset. Developmental delay is the common co morbid condition in IODM. Genetic diagnosis aids change of therapy to oral sulphonylurea.


Estimating selective advantage of two alleles in discrete time.
A class of estimators for the selective advantage, s, in a Wright-Fisher model with two alleles, variable population size, and genic selection is derived via martingale theory. Explicit expressions are given for these estimators which only involve simple computation. The optimal estimate among this class of estimators is obtained. Asymptotic results are readily established by an application of a martingale central limit theorem. The performance of this optimal estimator is compared to known estimators by means of a simulation study.


Bilateral Foreign Body Bronchus.
Foreign body of aerodigestive tract is one of the most common emergency which all the otolaryngologists do come across in the pediatric patients. Among the airway and digestive tract foreign bodies, airway foreign bodies always possess major risk. Only 47% cases will give a probable positive history. Most of the time the airway foreign bodies are radiolucent. Apart from the indirect signs like hyperinflation, collapse or pneumothorax there are no direct evidences regarding the type and number of foreign bodies on radiographs. The chances of having multiple foreign bodies in the same bronchus or in both the bronchi are not remote. Babies presenting with foreign bodies in bilateral bronchus have graver prognosis than the babies with unilateral foreign bodies. Here we want to share our experience in managing 7 cases of bilateral foreign body bronchus.


The H-reflex in the encephalopathy due to ammonia intoxication.
Ammonia intoxication has been shown to decrease excitatory synaptic transmission in several regions of the central nervous system. To investigate the relation between an effect of ammonia on excitatory synaptic transmission and the behavioral depression in the encephalopathy due to ammonia intoxication, this study examined in the rat the effects of ammonia intoxication on the H-reflex, the behavioral and neurological signs of the encephalopathy due to ammonia intoxication, and correlated the effects on the H-reflex with the signs of encephalopathy. Ammonia intoxication abolished the H-reflex without affecting the M-response. This indicated that ammonia intoxication decreased spinal excitatory synaptic transmission without affecting neuromuscular excitatory synaptic transmission. In the encephalopathy due to ammonia intoxication, the H-reflex disappeared only during a very advanced stage of behavioral depression, i.e., coma. During early stages of behavioral depression, i.e., during a decrease of reactions to sensory stimuli, the H-reflex was not affected by ammonia intoxication. Therefore, mechanisms other than a decrease of excitatory synaptic transmission in the central nervous system may be responsible for the behavioral depression seen in early stages of the encephalopathy due to ammonia intoxication.


Comparison of the efficacy of a distal clavicular locking plate versus a clavicular hook plate in the treatment of unstable distal clavicle fractures and a systematic literature review.
The purpose of this study was to retrospectively compare and review the clinical outcomes between the distal clavicular locking plate and clavicular hook plates in the treatment of unstable distal clavicle fractures; moreover, the relevant literature of the two fixation methods was reviewed systematically to identify the non-union, complications, or functional scores, according to the treatment methods and determine which treatment method is better. Sixty-six patients with 66 unstable distal clavicle fractures who underwent open reduction and internal fixation with either a distal clavicular locking plate (36 patients) or a clavicular hook plate (30 patients ) were evaluated. The main outcome comparisons included Constant score, rate of non-union, rate of complication, and rate of returning to work three months postoperatively. No significant difference was found between locking plate and hook plate groups in union rate and Constant score (P > 0.05). However, the results indicated that the distal clavicular locking plate group had a significantly lower rate of complications (P < 0.05) and symptomatic hardware (P < 0.05). In addition, the distal clavicular locking plate facilitated the return to work better than the clavicular hook plate (P < 0.05). Both distal clavicular locking plate and clavicular hook plate achieved good results in the treatment of unstable distal clavicle fractures; however, internal fixation with a distal clavicular locking plate had greater ability to return to their previous work after surgery in three months and fewer complications than the clavicular hook plate.