Hybrid Nanoassemblies from Viruses and DNA Nanostructures.
Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as "structured" genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.


Laparoscopic management of an internal double omental hernia: a rare cause of intestinal obstruction.
Internal hernia is a very rare cause of intestinal obstruction (0.2-0.9% of cases), associated with 45% mortality. A review of the literature revealed just eight reported cases of double omental hernia since 1950 of which our patient is the first case successfully treated laparoscopically. We report on a 29-year-old man who presented with signs and symptoms of intestinal obstruction. The patient underwent emergent exploratory laparoscopy. This revealed herniation of a 20-cm jejunal loop through the gastrocolic ligament and reemergence through a defect in the gastrohepatic ligament. The strangulated loop was reduced with slight traction, and the defect was repaired. The patient was discharged from hospital in just 5 days' time, and after 6 months of follow-up, the general condition of the patient was normal. Laparoscopy is a good technique with minimal complications compared with laparotomy. As many cases are missed due to nonspecific signs and symptoms, an urgent laparoscopy or laparotomy is highly recommended in such a situation.


Magnetic Properties of CeMn2-xCoxGe4O12 (0 ≤ x ≤ 2) as a Function of Temperature and Magnetic Field.
Polycrystalline samples, prepared by a solid-state route, of compositions in the solid solution CeMn2-xCoxGe4O12 (x = 0.0, 0.5, 1.0, 1.5, and 2.0) were characterized by X-ray diffraction, neutron diffraction, and magnetometry. They adopt space group P4/nbm with a ≈ 9.78 and c ≈ 4.85 Å and become anti-ferromagnetic (x = 0.0, 1.5, 2.0) or weakly ferromagnetic (x = 0.5, 1.0) at 4.2 ≤ T ≤ 7.6 K. The ordered moments lie along [001] when x = 0.0 and in the (001) plane otherwise. The unit cell doubles along [001] when x = 1.5 and 2.0 order anti-ferromagnetically, but the doubling is lost when a first-order metamagnetic transition to weak ferromagnetism occurs on the application of a 10 kOe magnetic field. The ordered moments at 1.6 K for x = 0.0 and 2.0 are 4.61(2) and 2.58(2) μB, respectively; the corresponding effective moments in the paramagnetic phase are 5.91 and 5.36 μB.


Difluorocarbene as a Building Block for Consecutive Bond-Forming Reactions.
Compounds containing a difluoromethylene unit have gained increasing attention due to their utility in drug design. Classic methods for the synthesis of these compounds rely on either harsh deoxofluorination reactions or laborious functional group manipulation sequences. In 2013, we proposed a method for assembling gem-difluorinated molecules from a difluorocarbene, a nucleophile, and an electrophile. In this process, a difluorocarbene can be considered an equivalent of a bipolar CF2 unit. Performing consecutive bond-forming reactions by sequential attachment of a nucleophile and an electrophile to a difluorocarbene provides the opportunity for the synthesis of a wide variety of organofluorine compounds. Silicon reagents were the most effective sources of the difluoromethylene fragment, and among them (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br) is the reagent of choice. Mildly basic activators such HMPA, DMPU, bromide and acetate ions can initiate the decomposition of the silane with concomitant generation of a difluorocarbene. Organozinc reagents can be employed as nucleophiles, and the CF2 fragment can insert into the carbon-zinc bond. Primary and secondary benzyl and alkyl organozinc compounds work well. Generally, organozinc reagents tolerate a variety of functional groups. The resulting fluorinated organozinc species can be coupled with heteroatom- or carbon-centered electrophiles. Halogenation of the carbon-zinc bond leads to compounds with bromo- or iododifluoromethyl fragments, which are difficult to access by other means, whereas protonation of that bond generates a valuable difluoromethyl group. Despite the decrease in the reactivity of the carbon-zinc bond caused by the adjacent fluorines, organozinc compounds can effectively participate in copper-catalyzed cross-couplings with allylic and propargyl halides, 1-bromoalkynes, and S-acyl dithiocarbamates. Difluorocarbene can be inserted into the carbon-silicon bond of trimethylsilyl cyanide, and the resulting silane can react with aldehydes and imines to furnish difluorinated nitriles. Interactions of difluorocarbene with heteroatom nucleophiles, such as phosphines or halide ions, are reversible, but the adduct can be trapped by an electrophile. The use of halide ions allows the direct nucleophilic bromo- and iododifluoromethylation of aldehydes and iminium ions. The combination of triphenylphosphine with difluorocarbene generates a difluorinated phosphorus ylide, which can interact with a wide range of π-electrophiles (aldehydes, ketones, acyl chlorides, azomethines, and Michael acceptors) to provide gem-difluorinated phosphonium salts. In the latter species, the carbon-phosphorus bond can be readily cleaved under basic conditions, affording the difluoromethylation products. Primary products resulting from three-component couplings can subsequently be used for further transformations. Single-electron reduction of carbon-phosphorus or carbon-iodine bonds can be conducted under photocatalytic conditions to generate gem-difluorinated radicals. These radicals can be trapped by silyl enol ethers leading to β,β-difluorinated ketones as the primary products. Fluorinated radicals can also undergo intramolecular attacks adjacent to an aromatic ring or a double bond.


Health status and public health education for internal older migrants in China: Evidence from a nationally representative survey.
Self-rated health has been widely used as a useful screening tool to subjectively evaluate individuals' health status. Under the context of the rapid growth of aging, there was a dramatic rapid expansion in internal older migrants in China. Serious concerns on the issues of health status continue to attract quite a lot of attention over the past decades. Public health education is one of the most important health care services and methods to improve individuals' health status. However, most previous studies focus on the utilization of public health services such as visiting to doctors, physical examination, and hospitalization. There was limited evidence on the self-rated health and public health education of older migrants. The study aimed to evaluate self-rated health and the associated determinants in older migrants, as well as to gain a deeper insight into the current status of public health education received by older migrants. We derived the data from the National Migrants Population Health and Family Planning Dynamic Monitor Survey 2018, a cross-sectional study, for secondary analysis. Internal migrants aged 60 years old or over were included in the study. Self-rated health was the dependent variable, while sociodemographic characteristics were the independent variable. The univariate and multivariate analyses were performed by Stata 15.1. A total of 5,589 older migrants were included in the study. Eighty-two percentage of older migrants reported healthy self-rated health. There was a significant association between age, gender, minzu, education level, monthly income, public health education, and self-rated health (P < 0.5). However, the proportion of older migrants that received specific public health education was <50%. The most common approach to receiving public health education was through the leaflet, while <20% of older migrants received public health education through public consultation and one-to-one education. It was necessary to promote the publicity of public health education in older migrants through easy access and diverse approaches in order to effectively spread health-related knowledge to older migrants to satisfy their health needs and maintain their health.


Selective inhibition of monoamine oxidase A by purpurin, an anthraquinone.
Monoamine oxidase (MAO) catalyzes the oxidation of monoamines that act as neurotransmitters. During a target-based screening of natural products using two isoforms of recombinant human MAO-A and MAO-B, purpurin (an anthraquinone derivative) was found to potently and selectively inhibit MAO-A, with an IC50 value of 2.50μM, and not to inhibit MAO-B. Alizarin (also an anthraquinone) inhibited MAO-A less potently with an IC50 value of 30.1μM. Furthermore, purpurin was a reversible and competitive inhibitor of MAO-A with a Ki value of 0.422μM. A comparison of their chemical structures suggested the 4-hydroxy group of purpurin might play an important role in its inhibition of MAO-A. Molecular docking simulation showed that the binding affinity of purpurin for MAO-A (-40.0kcal/mol) was higher than its affinity for MAO-B (-33.9kcal/mol), and that Ile 207 and Gly 443 of MAO-A were key residues for hydrogen bonding with purpurin. The findings of this study suggest purpurin is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a new potential lead compound for development of novel reversible inhibitors of MAO-A (RIMAs).


HIV and cardiovascular disease: the role of inflammation.
HIV and antiretroviral therapy (ART) use are linked to an increased incidence of atherosclerotic cardiovascular disease (ASCVD). Immune activation persists in ART-treated people with HIV (PWH), and markers of inflammation (i.e. IL-6, C-reactive protein) predict mortality in this population. This review discusses underlying mechanisms that likely contribute to inflammation and the development of ASCVD in PWH. Persistent inflammation contributes to accelerated ASCVD in HIV and several new insights into the underlying immunologic mechanisms of chronic inflammation in PWH have been made (e.g. clonal haematopoiesis, trained immunity, lipidomics). We will also highlight potential pro-inflammatory mechanisms that may differ in vulnerable populations, including women, minorities and children. Mechanistic studies into the drivers of chronic inflammation in PWH are ongoing and may aid in tailoring effective therapeutic strategies that can reduce ASCVD risk in this population. Focus should also include factors that lead to persistent disparities in HIV care and comorbidities, including sex as a biological factor and social determinants of health. It remains unclear whether ASCVD progression in HIV is driven by unique mediators (HIV itself, ART, immunodeficiency), or if it is an accelerated version of disease progression seen in the general population.


Effect of retinoic acid on gene expression profiles of bovine intramuscular preadipocytes during adipogenesis.
To investigate genes involved in intramuscular adipogenesis in ruminants, 16 genes with dramatic variable expression were selected. These were selected from the differentiation- and proliferation-phase libraries of our previous serial analysis of gene expression (SAGE) studies of a clonal bovine intramuscular preadipocyte (BIP) cell line. We harvested the BIP cells over 12 days after adipogenic stimulation with all-trans retinoic acid (ATRA). Quantitative real-time PCR confirmed the earlier SAGE study results of the expression patterns of 15 of the genes. On day 6, TG accumulation increased significantly in the BIP cells but was completely inhibited in the 3T3-L1 cells (the monogastric reference). ATRA enhanced expression levels of six genes whereas it suppressed expression of eight genes on day 3 of adipogenesis in the BIP cells. Forty-eight hours after transfection, the messenger RNA expression level of the adipose differentiation-related protein (ADFP), encoded by one of the upregulated genes, in the ADFP small interference RNA (siRNA)-transfected cells was 3.5% of that in negative control-transfected cells. Also, 6 days after induction the TG level in the ADFP siRNA-transfected cells was 21.8% lower than that in negative control-transfected cells. This analysis of gene expression profiles after ATRA treatment will contribute to our understanding of the molecular mechanisms involved in bovine intramuscular adipogenesis.


Combination drug strategies for biofilm eradication using synthetic and natural agents in KAPE pathogens.
Antibiotic resistance is a global threat caused by factors such as overuse of antibiotics, lack of awareness, development of biofilms etc. World Health Organization released a list of global priority pathogens which consisted of 12 species of bacteria categorized as expressing critical, high and medium resistance. Several Gram-negative and Gram-positive species are known to cause wide varieties of infections and have become multidrug or extremely drug resistant. Pathogens causing infections associated with invasive medical devices are biofilm producers and hence their treatment becomes difficult due to a structurally stable matrix which prevents antibiotics from penetrating the biofilm and thereby showing its effects. Factors contributing to tolerance are inhibition of penetration, restricted growth and activation of biofilm genes. Combination drug therapies has also shown potential to eradicate biofilm infections. A combination of inhaled Fosfomycin/tobramycin antibiotic strategy has been effective against Gram-negative as well as Gram positive organisms. Along with antibiotics, use of natural or synthetic adjuvants shows promising effects to treat biofilm infections. Fluroquinolone activity on biofilms is disrupted by low oxygen tension in the matrix, a strategy known as hyperbaric oxygen treatment that can enhance efficacy of antibiotics if well optimized. Adjuvants such as Ethylenediaminetetraacetic acid (EDTA), Sodium Dodecyl Sulphate (SDS) and chlorhexidine act by killing non-growing microbial cells aggregated on the inner layer of the biofilm. This review aims to list down current combination therapies used against Gram-negative and Gram-positive biofilm forming pathogens and brief about comparison of combination drugs and their efficacies.


Cervical Net: A Novel Cervical Cancer Classification Using Feature Fusion.
Cervical cancer, a common chronic disease, is one of the most prevalent and curable cancers among women. Pap smear images are a popular technique for screening cervical cancer. This study proposes a computer-aided diagnosis for cervical cancer utilizing the novel Cervical Net deep learning (DL) structures and feature fusion with Shuffle Net structural features. Image acquisition and enhancement, feature extraction and selection, as well as classification are the main steps in our cervical cancer screening system. Automated features are extracted using pre-trained convolutional neural networks (CNN) fused with a novel Cervical Net structure in which 544 resultant features are obtained. To minimize dimensionality and select the most important features, principal component analysis (PCA) is used as well as canonical correlation analysis (CCA) to obtain the best discriminant features for five classes of Pap smear images. Here, five different machine learning (ML) algorithms are fed into these features. The proposed strategy achieved the best accuracy ever obtained using a support vector machine (SVM), in which fused features between Cervical Net and Shuffle Net is 99.1% for all classes.


Role of nuclear receptor coactivator 3 (Ncoa3) in pluripotency maintenance.
Nuclear receptors, including Esrrb, Dax1, and Nr5a2, have been shown to be involved in pluripotency maintenance. Yet, the role of their coactivators in mouse embryonic stem cells remains unexplored. Here, we demonstrated that the nuclear receptor coactivator 3 (Ncoa3) is essential for pluripotency maintenance. Knockdown of Ncoa3 not only compromises the expression of pluripotency markers but also impairs in vitro and in vivo differentiation potential of mouse ESCs. Ncoa3 binds to the Nanog promoter and recruits the histone acetyltransferase CREB binding protein (CBP) and the histone arginine methyltransferase CARM1 to activate Nanog expression. Moreover, glycogen synthase kinase 3 GSK3 signaling down-regulates the Ncoa3 protein level to suppress Nanog expression. Thus, Ncoa3 not only contributes to self-renewal by activating Nanog but also facilitates ESC differentiation as a break point to disrupt the core transcriptional circuitry of pluripotency.


Disparities in access to and use of HIV-related health services in the Netherlands by migrant status and sexual orientation: a cross-sectional study among people recently diagnosed with HIV infection.
Migrants often face barriers to accessing healthcare. We examined disparities in access to and use of HIV-related health services between migrant and non-migrant people recently diagnosed with HIV living in the Netherlands, taken into account sexual orientation. Also, we examined differences in experiences in living with HIV between these groups. We used a questionnaire and clinical data collected between July 2013 and June 2015 among migrant and non-migrant participants of the European cross-sectional aMASE (Advancing Migrant Access to health Services in Europe) study in the Netherlands. Using univariable logistic regression analyses, we compared outcomes on between migrants and non-migrants, stratified by sexual orientation (with non-migrant men having sex with men [MSM] as the reference group). We included 77 migrant MSM, 115 non-migrant MSM, 21 migrant heterosexual men, 14 non-migrant heterosexual men and 20 migrant women. In univariable analyses, all heterosexual groups were less likely to ever have had an HIV-negative test before their diagnosis and were more likely to be diagnosed late than non-migrant MSM. All migrant groups were more likely to have experienced difficulties accessing general healthcare in the Netherlands and were less likely to have heard of post-exposure prophylaxis than non-migrant MSM. Migrants frequently reported uncertainty about their rights to healthcare and language barriers. Most (93%) participants visited a healthcare facility in the 2 years before HIV diagnosis but only in 41% an HIV test was discussed during that visit (no statistical difference between groups). Migrant heterosexuals were more likely to have missed appointments at their HIV clinic due to the travel costs than non-migrant MSM. Migrant MSM and women were more likely to have experienced HIV discrimination in the Netherlands than non-migrant MSM. Disparities in access to and use of HIV-related health services and experiences exist by migrant status but also by sexual orientation. Our data suggests heterosexual men and women may particularly benefit from improved access to HIV testing (e.g., through provider-initiated testing), while migrant MSM may benefit from improved access to HIV prevention interventions (e.g., pre-exposure prophylaxis).


Fluorescence polarization anisotropy to measure RNA dynamics.
RNA requires helical motion to fold and carry out its function. As RNA helical motion occurs on the nanosecond timescale, the timescale probed by fluorescence dyes, fluorescence polarization anisotropy (FPA) is a simple, yet powerful, technique to study helical dynamics in RNA. With the recent development of several fluorescent base analogs that have a nanosecond timescale lifetime in a duplex, FPA has begun to be used for characterizing RNA dynamics. Using the probe 6-methylisoxanthopterin (6-MI) as an example, we describe the procedure for carrying out FPA experiments on model oligonucleotide systems and in a complex RNA, the Tetrahymena group I intron. For smaller RNA systems, isolating the motion of the target helix from the overall tumbling of the whole RNA system is necessary, and nucleic acids binding proteins can be incorporated into the RNA system to increase the overall size of the system, slow the overall tumbling, and thereby reduce the anisotropy contribution from the overall tumbling to negligible. The procedure for incorporating one such protein, the Lac Repressor, is given as an example.


Effects of web-based interventions on cancer patients' symptoms: review of randomized trials.
Symptom management is of high priority in cancer care. Information and communication technology allows interventions to be provided through the internet to enhance the delivery of care. This study aimed to review the effects of web-based interventions on cancer patients' symptoms. MEDLINE, PSychINFO, PubMed, CINAHL, and Cochrane databases were systematically searched. Included were randomized controlled trials (RCTs), pilot RCTs, or quasi-experimental (QE) studies focusing on web-based interventions in adult cancer patients with at least one outcome primary or secondary, in terms of symptoms, treatment side effects, or distress. Data were analyzed study by study. Twenty studies were identified. All web interventions included information, 16 included self-management support, 14 included self-monitoring, 13 included feedback/tailored information, 12 used communication with health-care professionals, and eight used communication with other patients. Overall, 13 studies reported positive symptom outcomes. Psychological distress was reported in eight studies with positive intervention effects in three. Symptoms of anxiety/depression were reported in ten studies with positive intervention effects in five. Somatic symptom severity was reported in ten studies with intervention effects found in six, and symptom distress was reported in six studies with intervention effects found in all. This review shows the promising potential of web-based interventions for cancer symptom management, although it was limited by considerable heterogeneity in the interventions tested and targeted outcomes. The multidimensional nature of symptoms was partly addressed; only one study was guided by a comprehensive theoretical model of cancer symptom management. It can only be speculated which web elements are important for effective symptom outcomes. Further testing is needed for web-based cancer symptom management.


Tuberculosis, drug resistance, and HIV/AIDS: a triple threat.
The worldwide epidemics of tuberculosis (TB) and HIV/AIDS have been joined by an insidiously developing third epidemic of TB drug resistance. Fueled by the disruption of TB control programs and the explosive growth of HIV/AIDS, the presence of TB drug resistance, particularly multiple drug resistance, is worldwide and threatens the gains made in the past decades in the treatment of both TB and HIV. Although treatment success is possible, the diagnosis and treatment of drug-resistant TB is difficult. Advances in TB diagnosis and treatment have been minimal in the past 40 years, and there is an urgent need for wider distribution of available diagnostic technology and for the development and testing of newer rapid molecular diagnostic techniques and therapeutic agents. This review discusses current information about the distribution of multiple drug-resistant and newer extensively drug-resistant TB as well as available diagnostic and therapeutic strategies with an emphasis on the relationship between TB drug resistance and HIV/AIDS.


Establishment of a Successive Markerless Mutation System in Haemophilus parasuis through Natural Transformation.
Haemophilus parasuis, belonging to the family Pasteurellaceae, is the causative agent of Glässer's disease leading to serious economic losses. In this study, a successive markerless mutation system for H. parasuis using two sequential steps of natural transformation was developed. By the first homologous recombination, the target genes were replaced by a cassette carrying kanamycin resistance gene and sacB (which confers sensitivity to sucrose) gene using kanamycin selection, followed by the second reconstruction to remove the selection cassette, with application of sucrose to further screen unmarked mutants. To improve DNA transformation frequency, several parameters have been analyzed further in this work. With this method, two unmarked deletions in one strain have been generated successfully. It is demonstrated that this system can be employed to construct multi-gene scarless deletions, which is of great help for developing live attenuated vaccines for H. parasuis.


Acceleration of generalized replica exchange with solute tempering simulations of large biological systems on massively parallel supercomputer.
Generalized replica exchange with solute tempering (gREST) is one of the enhanced sampling algorithms for proteins or other systems with rugged energy landscapes. Unlike the replica-exchange molecular dynamics (REMD) method, solvent temperatures are the same in all replicas, while solute temperatures are different and are exchanged frequently between replicas for exploring various solute structures. Here, we apply the gREST scheme to large biological systems containing over one million atoms using a large number of processors in a supercomputer. First, communication time on a multi-dimensional torus network is reduced by matching each replica to MPI processors optimally. This is applicable not only to gREST but also to other multi-copy algorithms. Second, energy evaluations, which are necessary for the multistate bennet acceptance ratio (MBAR) method for free energy estimations, are performed on-the-fly during the gREST simulations. Using these two advanced schemes, we observed 57.72 ns/day performance in 128-replica gREST calculations with 1.5 million atoms system using 16,384 nodes in Fugaku. These schemes implemented in the latest version of GENESIS software could open new possibilities to answer unresolved questions on large biomolecular complex systems with slow conformational dynamics.


Dipole interaction model predicted pi-pi* circular dichroism of cyclo(L-Pro)3 using structures created by semi-empirical, ab initio, and molecular mechanics methods.
Cyclo(l-Pro)3 (CP3) is a synthetic peptide created to model cis and torsionally strained peptide bonds that also exhibits a strong distinctive UV circular dichroic (CD) spectrum. Circular dichroic spectra were computed for the amide pi-pi* transition using the dipole interaction model for various conformations of the peptide. Conformations of CP3 were created initially from crystal data, and followed by energy minimizations via molecular mechanics using the cvff force field; the effects of additional geometric optimizations by semi-empirical and ab initio quantum mechanics were investigated. The CD spectra for each conformation were calculated using a variety of different parameters, and each result was compared with the published experimental spectrum [Deber, C.M., Scatturin, A., Vaidya, V.M. & Blout, E.R. (1970) Small cyclic proline peptides: UV absorption and CD. In: Peptides: Chemistry and Biochemistry, Proceedings of the First American Peptide Symposium (Weinstein, B., ed.), Marcel Dekker, New York pp. 163-173]. Herein, two distinct conformations, a C3 symmetric and an asymmetric form, gave CD predictions that separately did not resemble the experimental spectrum. Energy differences were predicted at various theoretical levels, including MP2 and density functional theory. When the predicted CD spectra for each conformation were multiplied by Boltzmann weighting factors created using heats of formation determined by the AM1 optimizations, the weighted composite CD spectrum created did resemble experiment for the pi-pi* transition indicating that both conformations may exist simultaneously in solution.


Solution thermodynamic approach to analyze protein stability in aqueous solutions.
Protein thermal stability was analyzed by a solution thermodynamic approach. The small energetic differences in hydrogen-bonds (HB) among amino acid resdues and water molecules were proved to be amplified by the large number of HB involved to bring about the equilibrium shift from folding to unfolding of proteins. In aqueous solutions, water activity (Aw) plays a key role in protein stability. Therefore, Aw was precisely determined for various solutions and its relationship with solution structure was discussed. Wyman-Tanford analysis based on Aw showed linear regressions, without exception, between protein unfolding-ratio and Aw for lysozyme, ribonuclease A, and α-chymotrypsinogen A in various solutions with sugars, osmolytes, alcohols, and protein denaturant. From this linear regression, the free energy difference, ΔΔG, for a protein in a solution and in pure water, was easily obtained. Protein stability in a solution was proved to be determined by a balance between hydration and solute-binding effects to the protein and also by solution structure, which indirectly affects the hydrophobic interaction in a protein molecule. Temperature dependence of HB on protein stability suggested its interrelationship with hydrophobic interaction.


Pathogenic effects of D23N Iowa mutant amyloid beta -protein.
Cerebral amyloid beta-protein angiopathy (CAA) is a key pathological feature of patients with Alzheimer's disease and certain related disorders. In these conditions the CAA is characterized by the deposition of Abeta within the cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations have been identified within the Abeta region of the Abeta protein precursor (AbetaPP) gene that appear to enhance the severity of CAA. We recently described a new mutation within the Abeta region (D23N) of AbetaPP that is associated with severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697-705). In the present study, we investigated the effect of this new D23N mutation on the processing of AbetaPP and the pathogenic properties of Abeta. Neither the D23N Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing of AbetaPP expressed in H4 cells. The A21G Flemish mutation, in contrast, resulted in a 2.3-fold increase in secreted Abeta peptide. We also tested synthetic wild-type and mutant Abeta40 peptides for fibrillogenesis and toxicity toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch, D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Abeta40 peptides rapidly assembled in solution to form fibrils, whereas wild-type and A21G Flemish Abeta40 peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N Iowa Abeta40 peptides were found to induce robust pathologic responses in cultured HCSM cells, including elevated levels of cell-associated AbetaPP, proteolytic breakdown of smooth muscle cell alpha-actin, and cell death. Double mutant E22Q,D23N Dutch/Iowa Abeta40 was more potent than either single mutant form of Abeta in causing pathologic responses in HCSM cells. These data suggest that the different CAA mutations in AbetaPP may exert their pathogenic effects through different mechanisms. Whereas the A21G Flemish mutation appears to enhance Abeta production, the E22Q Dutch and D23N Iowa mutations enhance fibrillogenesis and the pathogenicity of Abeta toward HCSM cells.


[Kikuchi-Fujimoto necrotizing lymphadenitis. Report of 2 cases].
Kikuchi-Fujimoto disease (KFD) is a form of necrotizing lymphadenitis. The disease is a usually benign, self limited cause of lymph node enlargement affecting predominantly young women. Several other clinical manifestations have been described, though the only consistent findings are a macular eruption and a fever. Occasionally, the disease has presented as a fever of unknown origin. Lymph node specimens show areas of necrosis without neutrophilic infiltration. Lymphocyte mediated apoptotic mechanisms are responsible for the necrosis observed. Clinically, it should be differentiated from many different conditions, including infections such as cat scratch disease and rheumatological diseases like Still's disease and Systemic Lupus Erythematosus. Pathologically, it should be differentiated from lymphomas. KFD is widely known in the Far East, but very rare in Latin America. As a matter of fact, we have only detected four reported cases from Argentina, Brazil and Chile. We here describe two additional cases from Argentina. Both occurred in young women. One had a mediastinal compromise and a recurrent course, only observed in 4% of cases. The second one had a classical cervical presentation. The diagnosis in both was made by lymph node biopsy, although, in areas of great prevalence, an aspiration may be sufficient to establish the disease. We anticipate that the real prevalence of this unusual disease is highly underrepresented.


A miniature integrated multimodal sensor for measuring pH, EC and temperature for precision agriculture.
Making several simultaneous measurements with different kinds of sensors at the same location in a solution is difficult because of crosstalk between the sensors. In addition, because the conditions at different locations in plant beds differ, in situ measurements in agriculture need to be done in small localized areas. We have fabricated a multimodal sensor on a small Si chip in which a pH sensor was integrated with electrical conductivity (EC) and temperature sensors. An ISFET with a Si(3)N(4) membrane was used for the pH sensor. For the EC sensor, the electrical conductivity between platinum electrodes was measured, and the temperature sensor was a p-n junction diode. These are some of the most important measurements required for controlling the conditions in plant beds. The multimodal sensor can be inserted into a plant bed for in situ monitoring. To confirm the absence of crosstalk between the sensors, we made simultaneous measurements of pH, EC, and temperature of a pH buffer solution in a plant bed. When the solution was diluted with hot or cold water, the real time measurements showed changes to the EC and temperature, but no change in pH. We also demonstrated that our sensor was capable of simultaneous in situ measurements in rock wool without being affected by crosstalk.


Fluorescence and electrochemical sensing of pesticides methomyl, aldicarb and prometryne by the luminescent europium-3-carboxycoumarin probe.
This work describes the application of time resolved fluorescence in microtiterplates and electrochemical methods on glassy carbon electrode for investigating the interactions of europium-3-carboxycoumarin with pesticides aldicarb, methomyl and prometryne. Stern-volmer studies at different temperatures indicate that static quenching dominates for methomyl, aldicarb and prometryne. By using Lineweaver-Burk equation binding constants were determined at 303 K, 308 K and 313 K. A thermodynamic analysis showed that the reaction is spontaneous with ΔG being negative. The enthalpy ΔH and the entropy ΔS of reactions were all determined. A time-resolved (gated) luminescence-based method for determination of pesticides in microtiterplate format using the long-lived europium-3-carboxycoumarin has been developed. The limit of detection is 4.80, 5.06 and 8.01 μmol L(-1) for methomyl, prometryne and aldicarb, respectively. This is the lowest limit of detection achieved so far for luminescent lanthanide-based probes for pesticides. The interaction of the probe with the pesticides has been investigated using cyclic voltammetry (CV), differential pulse polarography (DPP), square wave voltammetry (SWV) and linear sweep voltammetry (LSV) on a glassy carbon electrode in I = 0.1 mol L(-1) p-toluenesulfonate at 25 °C. The diffusion coefficients of the reduced species are calculated. The main properties of the electrode reaction occurring in a finite diffusion space are the quasireversible maximum and the splitting of the net SWV peak for Eu(III) ions in the ternary complex formed . It was observed that the increase of the cathodic peak currents using LSV is linear with the increase of pesticides concentration in the range 5 × 10(-7) to 1 × 10(-5) mol L(-1). The detection limit (DL) were about 1.01, 2.23 and 1.89 μmol L(-1) for aldicarb, methomyl and prometryne, respectively. In order to assess the analytical applicability of the method, the influence of various potentially interfering species was examined. Influence of interfering species on the recovery of 10 μmol L(-1) pesticides has been investigated.


Gene chromosomal organization and expression in cultured human neurons exposed to cocaine and HIV-1 proteins gp120 and tat: drug abuse and NeuroAIDS.
As a model for Neuropsychiatric dysfunction in NeuroAIDS due to HIV-1 infection and drug abuse, we analyzed gene expression in human neurons treated with cocaine and HIV-1 proteins tat and envelope (env). One-way ANOVA showed statistically significant genes among the treatment groups (p < or = 0.0005). The identified genes were then subjected to a "stepwise" analysis using a repeated measures ANOVA to discover genes with parallel response group profiles across the treatment conditions. These groups were then analyzed using a repeated measures ANOVA to assess treatment main effects and gene-by-treatment interactions within groups. One-way ANOVA produced 35 genes that were significantly associated across all treatment conditions. Factorial analysis of each gene found statistically significant differences: 30--tat, 17--cocaine, 10--env, 6--tat/env, 6--coc/env, and 4--coc/tat. Analyses across genes found three sets of four genes, one set of three genes, and three sets of two genes with parallel profiles. Identified genes had functions included signaling, immune related, and transcription control. The genes were not stochastically arranged on the chromosomes, were in proximity to each other, and to other genes involved in neuropsychiatric diseases. We hypothesize that these genes fall in transcriptionally isolated groups and that abused drugs and HIV-1 proteins trigger transcription overload, coerced expression that may result in damage to the chromosome's control and organization of chromatin transcription machinery.


"Foreign brides" meet ethnic politics in Taiwan.
A great number of women from China, Vietnam, and Indonesia recently arrived in Taiwan to marry men of lower social strata. Such an unusual pattern of migration has stimulated debates about the status and the citizenship of the new arrivals. This study analyzes Taiwanese responses toward these marriage migrants by using a national survey conducted in 2004. Three aspects of restrictive attitudes were tapped concerning these newcomers: (1) rights to work; (2) access to public health insurance; and (3) full citizenship. Immigrants from China were most opposed, compared to women with other origins (Southeast Asia, Japan, Europe, and the US). The seemingly unrelated regression estimation regression results do not support the split labor market hypotheses, as marriage migrants do not appear to be economic threats toward members of the lower classes. In contrast, ethnic nationalism plays a key role in determining the natives' restrictive attitudes. The case of Taiwan represents a special genre, where ethnic politics selectively arouses the social rejection of women immigrants of certain origins.


Multiple injuries in vital organs in a child from a gunshot: a case report.
Many people in rural and urban areas own a gun legally or illegally. It is a social phenomenon that apart from the adults, the children become familiar with the guns in early age. A nine year old boy was shot by accident by his uncle, who was cleaning his gun (carbine) close to where the child was playing. More than 200 pellets were counted in the boy's x-rays. The boy was hospitalised in pediatric intensive care unit with many injuries in thorax, abdomen, and limbs, clearly shown by the x-rays. He developed multiple injuries in lungs and liver, bilateral haemothorax and pneumothorax, subcutaneous emphysema, injury of pericardium, perirenal hematoma, choloperitoneum, injuries in the intestine and in the limbs. Initial level of lead in the boy's body was measured as a reference value. Thereafter, frequent monitoring for lead levels was scheduled to prevent a potential lead poisoning from the pellets' absorption. After the appropriate treatment the boy left the hospital in a month in good health. The consequences from gun use in places where children are exposed could be fatal. The appropriate co-operation of different medical sub-specialities in Pediatrics and the presence of pediatric intensive care unit can save the life of a child with multiple injuries.


Malignancy in patients with sickle cell disease.
Malignancy in patients with sickle cell disease (SCD) has been previously reported, but the types of cancer and its incidence remain undefined. With the advent of hydroxyurea therapy, there is concern about increasing the cancer risk for patients with SCD. The International Association of Sickle Cell Nurses and Physician Assistants identified 52 cases of cancer (49 patients) among 16,613 patients with SCD followed at 52 institutions. The median age at malignancy diagnosis was 34 years (range, 14 months-62 years). Twenty-one cases (40%) occurred in pediatric patients, primarily leukemia (n = 7) or Wilms' tumor (n = 5), with 15 children surviving. Most adults had solid tumors, especially carcinomas, and only nine were known to be alive. Three patients received hydroxyurea before the diagnosis of malignancy. These data provide essential baseline information for the accurate interpretation of future reports of malignancy in patients with SCD, especially those receiving hydroxyurea therapy.


Implications of the primary prevention trials against coronary heart disease.
The bulk of the mortality (60%) in hypertension occurs in those with mild to moderate elevations of blood pressure, and the chief hazard is coronary disease. Although progression in the severity of hypertension has been slowed with drug therapy, the benefits for coronary outcome and all-cause mortality have been equivocal. Only a 10% reduction in coronary heart disease morbidity and mortality has been shown, an improvement that is not only small, but is statistically insignificant. Only vascular events such as renal failure, stroke, aortic dissection and cardiac failure have been reduced by antihypertensive therapy. Recent trials comparing beta-blockers with other antihypertensive drugs have failed to show the expected promise based on their effectiveness following a myocardial infarction. However, two large trials suggest that they may be effective against coronary heart disease in male non-smokers. A number of possible reasons for this therapeutic failure to reduce coronary heart disease have been postulated. The trials may have been too short to significantly affect the atherosclerotic progression. Also, sample sizes were too small to detect a sizeable reduction in coronary heart disease events. Furthermore, no attention was paid to improvements in the coronary heart disease risk profile, since drugs currently in use are known to have adverse effects on blood lipids, glucose tolerance and uric acid. It is even possible that a predisposition to sudden death is associated with antihypertensive therapy. The trials suggest that in attempts to prevent coronary heart disease, control of smoking and of serum lipids are particularly important in hypertensive persons and may be more effective than controlling the blood pressure alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolution of Tc-99m in diagnostic radiopharmaceuticals.
The progress in diagnostic nuclear medicine over the years since the discovery of 99mTc is indeed phenomenal. Over 80% of the radiopharmaceuticals currently being used make use of this short-lived, metastable radionuclide, which has reigned as the workhorse of diagnostic nuclear medicine. The preeminence of 99mTc is attributable to its optimal nuclear properties of a short half-life and a gamma photon emission of 140 keV, which is suitable for high-efficiency detection and which results in low radiation exposure to the patient. 99mTcO4-, which is readily available as a column eluate from a 99Mo/99mTc generator, is reduced in the presence of chelating agents. The versatile chemistry of technetium emerging from the 8 possible oxidation states, along with a proper understanding of the structure-biologic activity relationship, has been exploited to yield a plethora of products meant for morphologic and functional imaging of different organs. This article reviews the evolution of 99mTc dating back to its discovery, the development of 99Mo/99mTc generators, and the efforts to exploit the diverse chemistry of the element to explore a spectrum of compounds for diagnostic imaging, planar, and single photon emission computed tomography. A brief outline of the 99mTc radiopharmaceuticals currently being used has been categorically presented according to the organs being imaged. Newer methods of labeling involving bifunctional chelating agents (which encompass the "3 + 1" ligand system, Tc(CO)3(+1)-containing chelates, hydrazinonicotinamide, water-soluble phosphines, and other Tc-carrying moieties) have added a new dimension for the preparation of novel technetium compounds. These developments in technetium chemistry have opened new avenues in the field of diagnostic imaging. These include fundamental aspects in the design and development of target-specific agents, including antibodies, peptides, steroids, and other small molecules that have specific receptor affinity.


A permanent junctional reciprocating tachycardia with atypical location, treated with radiofrequency catheter ablation.
Permanent junctional reciprocating tachycardia (PJRT) is an incessant or almost incessant supraventricular tachycardia with a long RP interval, usually occurring in children and young adults. The differential diagnosis of PJRT includes an atrial tachycardia and atypical atrioventricular nodal reentrant tachycardia (AVNRT). The accessory pathways in PJRT are typically located in the posteroseptal region. We report a case of successful radiofrequency catheter ablation in a 28-year-old male patient with PJRT due to a left posterolateral accessory pathway.


Effectiveness of internet-based psychosocial interventions on psychological distress, expressed emotion, and knowledge about psychosis among family caregivers of people with schizophrenia: a systematic review protocol.
The objective of this review is to evaluate the effectiveness of internet-based psychosocial interventions versus active comparators (such as in-person interventions, bibliotherapy, or telephone interventions) and passive comparators (such as usual psychiatric care) on psychological distress, expressed emotion, and knowledge about psychosis in family caregivers of people with schizophrenia. Family caregivers of individuals with schizophrenia are at increased risk of developing mental disorders. Despite the widespread dissemination of reliable guidelines for caring for people with schizophrenia and their family caregivers, these have been poorly implemented. Hence, internet-based interventions with caregivers of people with schizophrenia could be an effective and feasible option. This review will include studies focusing on the family caregivers of individuals diagnosed with schizophrenia. Internet-based psychosocial interventions will be defined as any psychosocial intervention that is internet-based compared with active comparators (such as in-person interventions, bibliotherapy, or telephone interventions) and passive comparators (such as usual psychiatric care). The primary outcomes of this review will include psychological distress, expressed emotion, and knowledge about the psychosis of family caregivers of people with schizophrenia. The secondary outcome will be the hospitalization of people with schizophrenia. MEDLINE (PubMed), CINAHL (Ovid), Scopus, Cochrane Library, and ProQuest Dissertations and Theses will be systematically searched for published and unpublished studies from 2010 in English and Thai. Two reviewers will select studies, critically appraise them, and perform data extraction independently. Finally, when possible, the studies will be pooled through statistical meta-analysis and grading of the certainty of evidence by each outcome. PROSPERO CRD42021255318.


Antibacterial activity and interactions of plant essential oil combinations against Gram-positive and Gram-negative bacteria.
The aim of this study was to compare the antibacterial effects of several essential oils (EOs) alone and in combination against different Gram-positive and Gram-negative bacteria associated with food products. Parsley, lovage, basil, and thyme EOs, as well as their mixtures (1:1, v/v), were tested against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. The inhibitory effects ranged from strong (thyme EO against E. coli) to no inhibition (parsley EO against P. aeruginosa). Thyme EO exhibited strong (against E. coli), moderate (against S. typhimurium and B. cereus), or mild inhibitory effects (against P. aeruginosa and S. aureus), and basil EO showed mild (against E. coli and B. cereus) or no inhibitory effects (against S. typhimurium, P. aeruginosa, and S. aureus). Parsley and lovage EOs revealed no inhibitory effects against all tested strains. Combinations of lovage/thyme and basil/thyme EOs displayed antagonistic effects against all bacteria, parsley/thyme EOs against B. cereus, S. aureus, P. aeruginosa, and E. coli, and lovage/basil EOs against B. cereus and E. coli. Combinations of parsley/lovage and parsley/basil EOs exhibited indifferent effects against all bacteria. The combination of lovage/basil EO showed indifferent effect against S. aureus, P. aeruginosa, and S. typhimurium, and the combination parsley/thyme EO against S. typhimurium. Thyme EO has the highest percentage yield and antibacterial potential from all tested formulations; its combination with parsley, lovage, and basil EOs determines a reduction of its antibacterial activity. Hence, it is recommended to be used alone as the antibacterial agent.


Multiplex real-time PCR detection of pathogen colonization in the bark and wood of Picea sitchensis clones differing in resistance to Heterobasidion annosum.
A quantitative multiplex real-time polymerase chain reaction (PCR) procedure was developed to assess the extent of Heterobasidion annosum (Fr.) Bref. growth in Sitka spruce (Picea sitchensis (Bong.) Carr.) bark and wood and to determine correlations between lesion length and fungal colonization. Based on lesion length and real-time PCR, the responses of four 3-year-old Sitka spruce clones to inoculation with H. annosum were characterized as showing either resistance or susceptibility to the pathogen. In susceptible clones, the extent of bark colonization did not differ from the visible length of the bark lesion, whereas lesions were longer than the extent of fungal colonization in resistant clones. The resistant clones contained considerably less fungal DNA than the susceptible clones, relative to the amount of host DNA in both the bark and the wood, indicating less resistance and more host cell death in the susceptible clones following inoculation. In both resistant and susceptible clones, fungal colonization in the wood extended beyond the visible necrotic lesion in the bark, indicating that host defense responses are weaker in wood than in bark. The spread of the pathogen in both bark and wood was less in the resistant clones than in the susceptible clones, indicating that defenses in both bark and wood of the resistant clones were superior to those in the susceptible clones.


Application of regression analysis in the evaluation of tumor response following the administration of adriamycin either as a solution or via albumin microspheres to the rat.
Regression analysis has been applied to compare the tumor response following the administration of free and microsphere-loaded adriamycin to the rats. A nonmetastasizing sarcoma was induced in male A.S. inbred rats. When the sarcoma was in its fourth passage and 12 days old, four groups of animals received intratumoral injections of 2 or 8 mg/kg of adriamycin as a solution or via albumin microspheres. The animals in each group were monitored over a period of three weeks for changes in body weight and tumor size and their survival, and the results were statistically compared with the data obtained from an untreated group of animals (control). The use of regression analysis in conjunction with partial F-test revealed that the microsphere-delivered drug exhibited a meager but significantly greater response than the free drug. The implications of intratumoral administration of microsphere-loaded drug in the treatment of sarcomas is discussed.


Characterization of RNA-protein interactions in 7 S ribonucleoprotein particles from Xenopus laevis oocytes.
5 S RNA interactions with transcription factor protein A (TFIIIA) in 7 S particles from Xenopus laevis oocytes (Xlo) have been characterized by the use of an in vitro RNA exchange assay. 32P-labeled Xlo 5 S RNA can rapidly be incorporated into 7 S particles by simple incubation of the RNA with intact particles. Incorporation of the labeled RNA during exchange reaches an equilibrium within 20 min at 20 degrees C. Labeled Xlo 5 S RNA already incorporated in 7 S particles can be chased out by an excess of unlabeled 5 S RNA. Nondenaturing gel electrophoresis of 7 S particle samples segregates several ribonucleoprotein particles containing TFIIIA and 5 S RNA. Time course experiments reveal incorporation of 32P-labeled 5 S RNA first in a higher molecular weight ribonucleoprotein particle before incorporation into the 7 S particle. In the exchange process, the integrity of the higher order structure of the RNA is essential for a recognition of the 5 S RNA by TFIIIA. Denatured Xlo 5 S RNA exchanges poorly in the presence of EDTA, but can exchange into the particle at a high level if sufficient divalent cations are present to allow the higher order structure of the RNA to reform. Xlo 5 S RNA fragments that have the 5' or 3' ends deleted past helix I markedly lose their ability to exchange. Heterologous eukaryotic and eubacterial 5 S RNAs can exchange into 7 S particles, although the eubacterial 5 S RNAs exchange at a low level.


Comprehensive Gerontological Development: A Positive View on Aging.
Human aging can only be understood within its social and historical contexts. It is largely determined by the complex interrelation of biological, cultural, social, political, and economic factors. Furthermore, the phenomenon of population aging can be considered as a social and economic burden or as an invaluable social asset if understood within the perspective of the enormous potential of our aging populations. This article is based on the tenet that aging can be an enriching and productive stage marked by a lifelong process of personal growth and development. That is, in our perspective, ageing should become a process oriented toward the improvement and promotion of the individual's physical, psychological, and social potentialities to achieve the highest quality of life. The purpose of this article is to introduce the concept and practice of Comprehensive Gerontological Development that underlie current research at the Gerontological Research Unit of the Zaragoza Campus of the National Autonomous University of Mexico.


[Management of blood glucose--target of the management and its practice].
Accumulating evidence supports that management of blood glucose levels is critical for the prevention of diabetic vascular complications including macroangiopathy. Several therapeutic modalities are available in the management of blood glucose levels. In type 2 diabetes with obesity, achievement of body weight control with intensive caloric restriction is essential. Sulfonylurea remains the central drug in the management in insulin-independent patients without obesity. For patients with insulin resistance, biguanide or thiazolidinediones are the drugs of choice. For patients with postprandial hyperglycemia, a-glucosidase inhibitors and meglitinide analogs should be considered. Combination of some of these drugs has additive effect for patients with suboptimal blood glucose control with monotherapy. When the above therapies fail, we should not hesitate to start insulin.


Is abdominal wall tenderness a useful sign in the diagnosis of non-specific abdominal pain?
Pain arising from the abdominal wall has been implicated as a cause of non-specific abdominal pain (NSAP), and the presence of abdominal wall tenderness (AWT) has been proposed as an accurate diagnostic test for NSAP. One hundred and fifty eight patients admitted to hospital with abdominal pain were tested for the presence of positive AWT. In 53 patients the final diagnosis was appendicitis and positive AWT was found in five. Thirty eight patients were found to have a variety of other recognised pathological diagnoses, none of whom had a positive AWT. In 67 patients a diagnosis of NSAP was made in the absence of other pathological diagnosis, 19 of whom had positive AWT, which was significantly different from the other diagnostic groups. This study confirms the presence of AWT in up to 28% of patients with NSAP, and suggests that testing for AWT is of value in patients with abdominal pain, although a positive AWT is not as accurate a predictor of NSAP as previously reported.


Does Ageism Exist Among Multidisciplinary Rehabilitation Students? Predictors of Attitudes Toward Older Adults.
With the growing population of older adults, the demand for health rehabilitation services has rapidly increased. Like many countries around the world, the older population in Saudi Arabia is increasing. Tackling ageism has powerful provenance for uncovering and changing the dynamics of contemporary aging in Saudi Arabia. This study examined the attitudes toward older adults and the potential predictors influencing these attitudes among multidisciplinary health rehabilitation students. A total of 293 health rehabilitation students completed an online survey with a mean age of 21.1± 1.3 years. The survey included data about demographic and geriatric-related characteristics, attitudes toward older adults (UCLA-GA), knowledge of aging (FAQ) and aging anxiety (AAS). Most participants were female (70.3%), with 53% of the students specializing in physical therapy. The average score of attitudes toward older adults was 3.43 (0.40). The predictors of attitudes toward older adults were knowledge of aging (β = 0.34, p < 0.0001), living with older adults (β = 0.12, p = 0.02) and the importance of contact (very important, β = 0.31, p = 0.04). These results provide further evidence to support that ageist attitudes among students can be overcome by enhancing knowledge of aging and promoting positive contact with older adults. With the demographic shift in Saudi Arabia, we propose that there is a great need for establishing a competency-based geriatric education and strategies to enhance positive contact with older adults.


The role of metabolism in the immunogenicity of drugs: production of antibodies to a horseradish peroxidase generated conjugate paracetamol.
The allergic response to small chemically inert molecules in thought to require their enzymatic conversion to reactive metabolites which are then endowed with the capacity to bind covalently to host proteins and produce immunogenic hapten-carrier conjugates. In contrast to previous studies in which hapten-carrier conjugates have been generated following chemical modification of drugs we have examined the immunogenicity of paracetamol following direct conjugation to carrier proteins with horseradish peroxidase (HRP). Highly substituted conjugates of paracetamol with keyhole limpet haemocyanin (KLH) or bovine serum albumin (BSA) were generated using HRP. The KLH conjugate was used to immunize Balb/C mice. IgM and IgG (predominantly IgG1) responses were observed and shown by enzyme-linked immunosorbent assay (ELISA) to be hapten-specific. Manipulations of HRP levels permitted substitution of KLH to varying extents with paracetamol. Such conjugates were tested for their ability to induce a hapten-specific immune response. It was determined that substitution of 1 mol of KLH with 700 mol of paracetamol was sufficient to generate an anti-hapten response. These data suggest a mechanism by which protein-non-reactive drugs may be rendered immunogenic and provide a method for demonstrating the presence of serum antibodies reactive with drug metabolites.


Macroscopic dynamics near the isotropic-smectic-A phase transition.
The hydrodynamic theory for the smectic-A phase and the isotropic phase is generalized to the macroscopic dynamics in the vicinity of the isotropic-smectic-A phase transition. The macroscopic dynamic equations are presented on the isotropic side as well as on the smectic-A side of the phase transition, incorporating the effect of an external electric field. Specific experiments to test some of the effects contained in the macroscopic dynamic equations are suggested.


The short-term benefit and long-term failure of ultraviolet light in the treatment of venous leg ulcers.
Ultraviolet light has in the past been advocated for the treatment of venous leg ulcers on the assumption that it increases skin blood flow and reduces skin hypoxia. Our results show that UV light increases skin-oxygen tension of the lower leg and inhibits the normal vasoconstrictor response on standing. However, this effect is short lived and is followed after 2 days by a return of the vasoconstrictor reflex and a marked decrease in skin oxygenation which continues for at least 2 weeks. Since UV irradiation improves skin oxygenation for only 48 h, it cannot be recommended as a form of treatment for venous leg ulcers.


Facile Route to the Controlled Synthesis of Tetragonal and Orthorhombic SnO2 Films by Mist Chemical Vapor Deposition.
Two types of tin dioxide (SnO2) films were grown by mist chemical vapor deposition (Mist-CVD), and their electrical properties were studied. A tetragonal phase is obtained when methanol is used as the solvent, while an orthorhombic structure is formed with acetone. The two phases of SnO2 exhibit different electrical properties. Tetragonal SnO2 behaves as a semiconductor, and thin-film transistors (TFTs) incorporating this material as the active layer exhibit n-type characteristics with typical field-effect mobility (μ(FE)) values of approximately 3-4 cm(2)/(V s). On the other hand, orthorhombic SnO2 is found to behave as a metal-like transparent conductive oxide. Density functional theory calculations reveal that orthorhombic SnO2 is more stable under oxygen-rich conditions, which correlates well with the experimentally observed solvent effects. The present study paves the way for the controlled synthesis of functional materials by atmospheric pressure growth techniques.


Thermogenic properties of ciclazindol and mazindol in rodents.
Ciclazindol, a noradrenaline (NA) uptake inhibitor originally introduced as an antidepressant, has recently been shown to produce weight loss in experimental animals and patients. Unlike CNS-stimulant anti-obesity drugs, such as amphetamine, ciclazindol may induce weight loss in animals by stimulating thermogenesis in brown adipose tissue (BAT), and it is known to stimulate resting metabolic rate (RMR) of rats and depress energetic efficiency. These effects can be achieved in the absence of overt CNS stimulation and with certain analogues of ciclazindol may be due to an exclusive peripheral action. Mazindol, a structural analogue of ciclazindol also produces an increase in RMR. However the increment is qualitatively and quantitatively different from that observed with ciclazindol and cannot be dissociated from central stimulant actions. In this report we examine some of the physiological and behavioural effects of ciclazindol and mazindol analogues in rats.


Effect of cyclosporine on blood pressure.
Cyclosporine is an immunosuppressive agent used for different autoimmune diseases. The official Canadian indications for cyclosporine are solid organ transplantation, bone marrow transplantation, psoriasis, rheumatoid arthritis and nephritic syndrome (e-CPS 2008). The expanding range of indications for cyclosporine therapy will lead to more patients receiving chronic therapy with possible side effects, hypertension being one of the most common. Therefore it is essential to know the magnitude of increase of blood pressure (BP) associated with cyclosporine in order to appropriately manage patients receiving the drug. The primary objective of this systematic review is to evaluate the effect of cyclosporine on blood pressure, compared to placebo in randomized trials. We searched The Cochrane Central Register of Controlled Trials (CENTRAL) and bibliographic databases, including MEDLINE (2000-2008) and EMBASE (1980-2008). Selection was made using double-blind, randomized, controlled trials comparing cyclosporine to placebo. All patients treated with cyclosporine were included without restriction by type of disease or by age and sex. Blood pressure measurements in any setting and by any means were acceptable including the auscultatory or oscillometric method with a preference for the sitting position. Mean blood pressure results were entered as mean change from placebo and standard error of the mean (SEM). If blood pressure data was provided at different times after the initiation of cyclosporine therapy the weighted mean BP change from placebo from all measurements was used. The search yielded 1340 citations, of which 17 trials met the inclusion criteria. We created dose-ranges according to the usual dose administration recommended by the manufacturer and allocated the 17 included trials to the corresponding dose-range. The results demonstrate a highly statistically significant increase in blood pressure associated with cyclosporine. There appears to be a dose-related effect with lower doses (1-4 mg/kg/d) increasing mean BP by an average of 5 mmHg and higher doses (>10 mg/kg/d) increasing mean BP by 11 mmHg on average. Furthermore in 3 trials the effect appears to be similar after a single dose as with chronic therapy. Cyclosporine statistically significantly increases blood pressure compared to placebo in a dose-related fashion. The magnitude of increase in blood pressure is clinically significant and increases the risk of stroke, myocardial infarction, heart failure and other adverse cardiovascular events associated with elevated BP. Consequently prescribers should try to find the lowest effective dose in all patients receiving cyclosporine chronically.


The granulate ambrosia beetle, Xylosandrus crassiusculus (Coleoptera: Curculionidae, Scolytinae), and its fungal symbiont found in South Africa.
Xylosandrus crassiusculus (Motchulsky) is a native Asian ambrosia beetle that has been accidentally introduced to many countries of the world, presumably through the international movement of nursery, timber, and wood products. The species is known in various tropical African countries but only as far south as Tanzania on the African continent. In this study, we report X. crassiusculus and its fungal symbiont for the first time from South Africa. The species was identified using both morphological characters and COI sequence data. Xylosandrus crassiusculus were obtained from three different provinces of South Africa and represent two distinct haplotypes. The fungal symbiont, Ambrosiella roeperi, was isolated and identified using DNA sequencing and morphological characterization.


Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report.
Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. We report the case of an 8-year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein--AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis.


Unity yield of deterministically positioned quantum dot single photon sources.
We report on a platform for the production of single photon devices with a fabrication yield of 100%. The sources are based on InAsP quantum dots embedded within position-controlled bottom-up InP nanowires. Using optimized growth conditions, we produce large arrays of structures having highly uniform geometries. Collection efficiencies are as high as 83% and multiphoton emission probabilities as low as 0.6% with the distribution away from optimal values associated with the excitation of other charge complexes and re-excitation processes, respectively, inherent to the above-band excitation employed. Importantly, emission peak lineshapes have Lorentzian profiles indicating that linewidths are not limited by inhomogeneous broadening but rather pure dephasing, likely elastic carrier-phonon scattering due to a high phonon occupation. This work establishes nanowire-based devices as a viable route for the scalable fabrication of efficient single photon sources and provides a valuable resource for hybrid on-chip platforms currently being developed.


Surveillance of Jaagsiekte sheep retrovirus in sheep in Hokkaido, the northern island of Japan.
Surveillance of jaagsiekte sheep retrovirus (JSRV) infection was performed by polymerase chain reaction (PCR) of blood DNA samples collected from 40 sheep and goats in 10 different flocks in Hokkaido, the northern island of Japan. No exogenous (oncogenic) JSRV sequence was detected by PCR in these samples, while the ovine endogenous retrovirus sequence was successfully amplified in all samples. Our paper is the first demonstration of JSRV surveillance in Japan and shows no evidence of oncogenic JSRV infection in sheep and goats in Hokkaido.


Repression predicts outcome following multidisciplinary treatment of chronic pain.
This study examined whether repression predicts outcome following multidisciplinary treatment for chronic pain and whether links between anxiety and outcome are obscured by repressors. Ninety-three chronic pain patients completed a 4-week pain program. Lifting capacity, walking endurance, depression, pain severity, and activity were measured at pre- and posttreatment. Low-anxious, repressor, high-anxious, and defensive/high-anxious groups were formed from median splits of Anxiety Content (ACS) and Lie scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Significant ACS x Lie interactions were found for lifting capacity, depression, and pain severity changes. Planned comparisons showed that both repressors and high-anxious patients performed poorly on lifting capacity; repressors alone recovered poorly on depression and pain severity. Results imply that repression may interfere with the process and outcome of pain programs.


[Gastric secretory, ultrastructural and pH changes during prolonged treatment with omeprazole in a severe form of Zollinger-Ellison syndrome].
Omeprazole, a powerful and long-lasting gastric anti-secretory benziimidazole derivative has been used to treat a particularly severe case of Zollinger-Ellison syndrome with familial type I multiple endocrine involvement. Before treatment with omeprazole, the patient's basal acid secretion, ranging from 50 to 100 mmol/h, had been poorly controlled by cimetidine (doses of up to 2,400 mg/d), ranitidine (doses of up to 1,200 mg/d) and even by ranitidine (1,200 mg/d) combined with pirenzepine (150 mg/d). Upon oral administration of four 20-mg capsules of omeprazole twice daily, rapid healing of the diffuse mucosal ulcerations of the upper GI tract as well as control of diarrhea were achieved. Clinical benefit accompagnied dramatic and sustained reductions in gastric acid secretion as demonstrated by repeated basal output measurements and 24-hour intragastric pH recording. The biodisponibility of omeprazole improved as gastric intraluminal acidity was reduced. The effects of omeprazole on pepsin output appeared to be mainly related to the reduction of gastric secretory volume. After more than one year of treatment, neither clinical nor biological side-effects were noted. However, repeated ultrastructural studies of fundic gastric mucosa revealed two types of alterations: a) a pattern of hyper-stimulated parietal cells with turgescent intra-cellular micro-canalicus invested by numerous microvilli; b) in about a fourth of the parietal cells, cytoplasmic modifications resembling auto-phagosomia and mitochondrial reduction in number and morphological transformation. Poorly understood to date, these alterations call for regular histological control of the gastric mucosa in patients with Zollinger-Ellison syndrome submitted to long-term administration of large doses of omeprazole.


Prolongation of islet xenograft survival without continuous immunosuppression.
The survival of isolated rat islets transplanted into diabetic mice was prolonged markedly by maintaining the rat islets in vitro at 24 degrees C for 7 days before transplantation and administering to the recipients a single injection of antiserum to mouse and rat lymphocytes shortly before transplantation.


Effect of a 6-week and 12-week cardiac rehabilitation program on heart rate recovery.
Cardiac rehabilitation has been shown to reduce cardiac mortality, improve quality of life, and reduce hospitalizations. Cardiac rehabilitation programs are usually performed over a 12-week period. Studies have shown that similar benefits could be achieved with shorter programs. Abnormal heart rate recovery after exercise has been associated with an increased risk of cardiovascular events and mortality. The main aim of this study was to compare the effect of a 6-week phase 2 cardiac rehabilitation program on heart rate recovery to a 12-week one in patients who had recovered from an anterior wall ST segment elevation myocardial infarction. This prospective study included 60 patients enrolled in cardiac rehabilitation programs randomized into two equal groups: a 6-week and a 12-week program. Baseline patient demographics, lipid profile, and left ventricular ejection fraction (LVEF) were assessed. METs achieved, total exercise time, resting heart rate, peak heart rate, and heart rate recovery at 1 min were examined. These were re-assessed at the end of each program. Results showed no difference between both groups at the end of each program regarding lipid profile and LVEF. Patients enrolled in the 12-week cardiac rehabilitation program were able to achieve more METs, had a longer exercise time, a higher peak heart rate, and had a lower resting heart rate at the end of the program. Heart rate recovery was slightly higher in patients enrolled in the 6-week program 26.5 ± 6.78 versus 23.17 ± 6.12 bpm (p = 0.051). On comparing the magnitude of change between both programs, those in the 12-week program had more increase in HDL-C levels, METs achieved, and exercise time. Additionally, they had more reduction of resting heart rate. Heart rate recovery was more increased for those in the 6-week program. Although heart rate recovery increases after completion of each of a 6-week and 12-week cardiac rehabilitation program compared to their baseline, there is no difference on comparing heart rate recovery between both programs at their end. Patients enrolled in a standard 12-week cardiac rehabilitation program achieve more METs, have a longer exercise time, a higher peak HR, and a lower resting HR at the end of the program compared to those in the 6-week program.


Dosimetric impact of esophagus motion in single fraction spine stereotactic body radiotherapy.
Nine patients with single fraction spinal stereotactic body radiation therapy (SBRT) treatment were identified to assess both the intra fraction and daily esophageal motion and associated dosimetric deviation in spinal SBRT. We performed a chained deformable registration of 4D CT phase images to estimate the intra fraction motion magnitude of the esophagus in a breathing cycle. The intra fraction esophageal motion mostly exhibited in the superior-inferior direction with the total motion magnitude increased from the T1 (0.7 mm) to the T11 vertebra level (6.5 mm). The actual dose received by a moving esophagus was estimated by accumulating dose from each phase of the 4D dataset using deformable image registration. In comparison, dose recalculated on the average CT reflects the dose received by a stationary esophagus. Intra fraction motion was found to reduce the maximum dose received by a small volume of esophagus ⩽2 cm3, with the largest absolute and relative dose difference being -80 cGy and -6.4%, respectively. Its effect on the maximum dose received by 5 cm3 of esophagus can be higher or lower with a large percentage difference, but did not result in substantial absolute dose increase to violate the dose constraint of 11.9 Gy we used for plan evaluation. In addition, there was no correlation between the dosimetric deviation and the intra fraction motion magnitude. These findings suggest that 4D CT simulation is not essential with regards to the esophageal dose. The daily motion of the esophagus and its dosimetric impact was investigated by examining the difference of esophagus delineated on both treatment and planning CT after they were registered using boney target. The day to day difference of esophagus was negligible for all cases in this study.


Catalytic ozonation of sulfamethoxazole using low-cost natural silicate ore supported Fe2O3: influencing factors, reaction mechanisms and degradation pathways.
A low-cost natural silicate ore supported Fe2O3 (FeSO) was synthesized for catalytic ozonation of sulfamethoxazole (SMX). XRD, SEM-EDS, BET, FTIR and XPS results of the FeSO catalyst confirmed that the natural silicate ore was successfully modified with iron oxide. The effects of key factors, such as catalyst dosage, initial solution pH, reaction temperature, inorganic anions and initial concentration, on ozonation degradation were systemically investigated. The degradation rate of SMX (20 mg L-1) was 88.1% after 30 min, compared with only 35.1% SMX degradation rate in the absence of the catalyst, and the total organic carbon (TOC) removal reached 49.1% after 60 min. Reaction mechanisms revealed that surface hydroxyl groups of FeSO were a critical factor for hydroxyl radical (˙OH) production leading to fast SMX degradation in the ozone decomposition process. The degradation products were detected, and the possible pathways of SMX were then proposed. This study provides guidance for preparing a low-cost catalyst and analyzing the degradation products and pathways of SMX in the ozonation process, which is of significance in practical industrial applications.


Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review.
Grapes are one of the most widely grown fruits and have been used for winemaking since the ancient Greek and Roman civilizations. Grape seeds are rich in proanthocyanidins which have been shown to possess potent free radical scavenging activity. Grape seeds are a complex matrix containing 40% fiber, 16% oil, 11% proteins, and 7% complex phenols such as tannins. Grape seeds are rich sources of flavonoids and contain monomers, dimers, trimers, oligomers, and polymers. The monomeric compounds includes (+)-catechins, (-)-epicatechin, and (-)-epicatechin-3-O-gallate. Studies have reported that grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Their potential health benefits include protection against oxidative damage, and anti-diabetic, anti-cholesterol, and anti-platelet functions. Recognition of such health benefits of proanthocyanidins has led to the use of grape seeds as a dietary supplement by the consumers. This paper summarizes the studies of the phytochemical compounds, pharmacological properties, and industrial applications of grape seeds.


Faecal dry matter excretion per se affects faecal calcium and phosphorus losses in dogs.
The study aimed to investigate the effect of faecal dry matter (DM) excretion on faecal losses of calcium (Ca) and phosphorus (P) without potentially confounding factors. Dogs were fed two levels of the same basal diet (cooked pork, rice, gelatine; 8.5 ± 0.7 and 12.6 ± 1.2 g DM/kg BW). Mineral supplements were added separately for identical Ca and P supply independent of DM intake (Ca 226 and P ~170 mg/kg BW). Digestion trials (10 days adaptation, 5 days quantitative faecal collection) were carried out. Digestibility of DM averaged 87% in both trials. Faecal DM and mineral excretion increased highly significant (DM 1.1 ± 0.3 to 1.7 ± 0.2 g/kg BW, p = 0.00005; Ca 185 ± 34 and 233 ± 22 mg/kg BW, p = 0.00119; P 99 ± 23 to 127 ± 12 mg/kg BW, p = 0.00212), revealing a highly significant correlation. Apparent digestibility of Ca was positive in the first trial and negative in the second leading to a slightly negative Ca retention in the latter one. The results suggest that in dogs (i) factors influencing Ca and P absorption can only be compared if faecal DM excretion is identical and (ii) Ca requirements may be affected by DM intake and digestibility.


Abrupt hemodynamic changes accompanying intrapleural hyperthermic chemotherapy: Case series.
Intrapleural hyperthermic chemotherapy (IPHC) is the preferred method to locally treat lung cancer with pleural seeding. Anesthetic management during IPHC is a very challenging task for the anesthesiologist because of the hemodynamic instability associated with the procedure; however, there is no report on anesthetic considerations during the IPHC procedure. Three patients who diagnosed lung cancer with pleural invasion scheduled for IPHC were reported in this case series. Case 1, a 48-year-old woman, suffered from lung cancer (adenocarcinoma, T2NxM1a) with diffuse pleural seeding. Case 2, a 58-year-old female, diagnosed with lung cancer (adenocarcinoma, T3N0M1a) with pleural dissemination. Case 3, a 47-year-old male, diagnosed as sarcoma on the left lung with right pericardial invasion and right hemidiaphragm invasion (stage, T3N0M1a). All three patients underwent IPHC with cisplatin diluted in normal saline (2000 ml) at a rate of 600 ml/min. Inflow temperature of 42°C was using a heart-lung machine over 90 minutes. Hemodynamic changes were monitored through the procedure. The patient did not require supplemental oxygenation anymore after he recovered from lung transplantation. There was sudden drop in the cardiac output and an increase in the pulmonary vascular resistance, which were caused by the volume and temperature of the hyperthermic chemotherapeutic drugs in the pleura during the early stage of IPHC; these changes can be a major problem during the procedure, and supportive hemodynamic management may be needed.


Using risk factors and markers to predict bacterial respiratory co-/superinfections in COVID-19 patients: is the antibiotic steward's toolbox full or empty?
Adequate diagnosis of bacterial respiratory tract co-/superinfection (bRTI) in coronavirus disease (COVID-19) patients is challenging, as there is insufficient knowledge about the role of risk factors and (para)clinical parameters in the identification of bacterial co-/superinfection in the COVID-19 setting. Empirical antibiotic therapy is mainly based on COVID-19 severity and expert opinion, rather than on scientific evidence generated since the start of the pandemic. We report the best available evidence regarding the predictive value of risk factors and (para)clinical markers in the diagnosis of bRTI in COVID-19 patients. A multidisciplinary team identified different potential risk factors and (para)clinical predictors of bRTI in COVID-19 and formulated one or two research questions per topic. After a thorough literature search, research gaps were identified, and suggestions concerning further research were formulated. The quality of this narrative review was ensured by following the Scale for the Assessment of Narrative Review Articles. Taking into account the scarcity of scientific evidence for markers and risk factors of bRTI in COVID-19 patients, to date, COVID-19 severity is the only parameter which can be associated with higher risk of developing bRTI. Evidence on the usefulness of risk factors and (para)clinical factors as predictors of bRTI in COVID-19 patients is scarce. Robust studies are needed to optimise antibiotic prescribing and stewardship activities in the context of COVID-19.


Human subcutaneous dirofilariasis, Russia.
We report 14 cases of human subcutaneous dirofilariasis caused by Dirofilaria repens, diagnosed from February 2003 through July 2004, in patients from Rostovon-Don, Russia. Serologic analysis showed evidence of high risk of exposure to D. repens. Surveillance studies on prevalence and prevention effectiveness of canine infection are needed to control this emerging zoonosis.


Cirrhilabruswakanda, a new species of fairy wrasse from mesophotic ecosystems of Zanzibar, Tanzania, Africa (Teleostei, Labridae).
Cirrhilabruswakanda sp. nov. is described on the basis of the holotype and four paratypes collected between 50 and 80m depth over low-complexity reef and rubble bottoms at the east coast of Zanzibar, Tanzania, Africa. The new species belongs to a group of fairy wrasses from the western Indian Ocean, sharing a combination of characters that include: short pelvic fins (not or barely reaching anal-fin origin); relatively unmarked dorsal and anal fins; males with a strongly lanceolate caudal fin (except in C.rubrisquamis); both sexes with a pair of prominent facial stripes above and below the orbit; and both sexes with prominent purple scales and osseus elements that persist, and stain purple, respectively, even in preservation. This group of fairy wrasse is part of a larger complex that includes related species from the western Pacific Ocean. In addition to meristic and morphometric comparisons, we also compare mitochondrial DNA sequence data to the aforementioned, putatively related species.


Investigation of expression of HOX 2C and HOX 4B homeobox genes in human colorectal cancer by using an RT-PCR method.
Investigation of expression of both HOX 2C and HOX 4B homeobox genes in the same patient with colorectal cancer was proposed by using an RT-PCR method. In order to conduct this investigation, PCR products of 445 bp of HOX 2C and 301 bp of HOX 4B were amplified in both tumor and normal samples of ten patients. Expressions of HOX 2C gene were observed in both tumor and normal samples of four patients and in only a tumor sample of one patient, while the expression was not observed in both tumor and normal samples of five patients. Expressions of HOX 4B gene were not observed in both tumor and normal samples of ten patients. In the present study, it was found that individuality seems to be important. The results of these two genes, observed in patients with colorectal cancer, should be taken into consideration for further researches.


Psychosocial impact, perceived stress and learning effect in undergraduate dental students during transition from pre-clinical to clinical education.
This study aimed to develop a suitable instrument for a comprehensive quantitative and qualitative assessment of perceived psychosocial impact, levels of stress and learning effect in undergraduate dental students during the transition from pre-clinical to clinical education. These findings might improve curricular structures and didactic organisation during this period. At the beginning of their first clinical year, undergraduate dental students were asked to complete an anonymous forty-item questionnaire. Two hundred and seventy-six undergraduate dental students were willing to participate and completed the questionnaire and participated during the years 2011-2016. The response rate was between 45% and 96%. Correlational analysis (Spearman-Rho) in the field of psychosocial impact showed the dental teacher to be the most important multiplier of students' feelings. If the students feel that their teacher acts cooperatively, positive items increase and negative items decrease significantly (P < .0001). Also, students who report high levels of stress are affected significantly in their psychosocial interaction (P < .0001). Wilcoxon test yielded highest levels of stress in endodontology during the first weeks (P < .0001). During the same period, the greatest learning increment was seen for diagnostics and caries excavation. In conclusion, teaching of undergraduate dental students during the transition period from pre-clinical to clinical education can be positively influenced by a supportive learning environment and by specific chronological modifications in the curriculum. Students should start their clinical training with diagnostics, preventive dentistry and initial periodontal treatment. Due to high levels of perceived stress, endodontology should be introduced later in the clinical curriculum.


Diagnosis of abdominal tuberculosis in Christchurch New Zealand: a case series.
Abdominal tuberculosis presents with non-specific symptoms, including generalised abdominal pain. Prompt and accurate diagnosis is critical to improving outcomes and avoiding complications. We conducted a retrospective review of cases of abdominal tuberculosis presenting to Christchurch Hospital to explore the epidemiology, clinical features and diagnostic modalities used. Cases were identified by searching for relevant ICD discharge codes from January 1996 to January 2016. Data on age, clinical presentation, investigations and microbiological results were obtained. There were 20 patients diagnosed with abdominal tuberculosis over the study period. The median age was 34. Thirteen patients were male (65%), seven female (35%). The majority (11) were from Asia (predominantly India), five were African, and three were New Zealand Europeans. Abdominal pain was the most common presenting symptom (70%) followed by fevers (50%) and night sweats (50%). The C-reactive protein was elevated in 15 patients (75%), anaemia was found in 11 (55%) and nine had abnormal liver function tests (45%). Abdominal ultrasound (US) and computed tomography (CT) showed generic inflammatory change in all patients in this series (100%). Laparoscopy was undertaken in 10 (50%) patients, all of which had positive laparoscopic biopsies. Ascitic fluid was obtained in nine, with stains for acid-fast bacilli uniformly negative, however three (33%) had mycobacterial growth from culture. Six colonoscopies were performed: in three (50%) culture and/or histology was positive. Three lymph node biopsies and two formal laparotomies were the remaining diagnostic techniques employed with two biopsies and one laparotomy yielding positive results. Overall, of the 20 cases, 15 (75%) were able to be definitively confirmed, with the remaining five treated presumptively for probable abdominal tuberculosis. Abdominal tuberculosis is an uncommon presentation at our institution, with an average of one case each year. The typical patient was a young immigrant from Asia or Africa. Diagnostic laparoscopy was the most common and uniformly reliable means of obtaining a definitive diagnosis.


Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1, and SLC23A2 and risk for preterm delivery.
Vitamin C has been the focus of epidemiologic investigation in preterm delivery (<37 weeks' gestation), which is a leading cause of neonatal mortality and birth-related morbidity. There are two sodium-dependent membrane transporters encoded by SLC23A1 and SLC23A2, which have key roles in human vitamin C metabolism and which control dietary uptake, reabsorption, and tissue distribution of vitamin C. Using maternal DNA, the authors evaluated common single-nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2 in a nested case-control analysis of the Pregnancy, Infection, and Nutrition Study (1995-2000) cohort. Of the associations observed for both haplotypes in SLC23A1 and individual SNPs in SLC23A2, the most robust finding is with an intron 2 variant in SLC23A2. Heterozygotes and homozygotes for this variant had a 1.7-fold (95% confidence interval: 0.9, 3.3) and a 2.7-fold (95% confidence interval: 1.2, 6.3) elevation in the risk of spontaneous preterm birth, respectively. Semi-Bayesian hierarchical regression analysis, which simultaneously adjusted for multiple SNPs within the same gene, gave comparable results. The authors' findings link genetic variants in the vitamin C transporters to spontaneous preterm birth, which may explain previous dietary associations. If the findings from this study are confirmed, they may serve as the foundation for genetic risk assessment of nutritional pathways in preterm birth.


Gelatin- and Papaya-Based Biodegradable and Edible Packaging Films to Counter Plastic Waste Generation.
Most of the food packaging materials used in the market are petroleum-based plastics; such materials are neither biodegradable nor environmentally friendly and require years to decompose. To overcome these problems, biodegradable and edible materials are encouraged to be used because such materials degrade quickly due to the actions of bacteria, fungi, and other environmental effects. In this work, commonly available household materials such as gelatin, soy protein, corn starch, and papaya were used to prepare cost-effective lab-scale biodegradable and edible packaging film as an effective alternative to commercial plastics to reduce waste generation. Prepared films were characterized in terms of Fourier transform infrared spectroscopy (FTIR), water vapor transmission rate (WVTR), optical transparency, and tensile strength. FTIR confirmed the addition of papaya and soy protein to the gelatin backbone. WVTR of the gelatin-papaya films was recorded to be less than 50 g/m2/day. This water vapor barrier was five times better than films of pristine gelatin. The gelatin, papaya, and soy protein films exhibited transparencies of around 70% in the visible region. The tensile strength of the film was 2.44 MPa, which improved by a factor of 1.5 for the films containing papaya and soy protein. The barrier qualities of the gelatin and gelatin-papaya films maintained the properties even after going through 2000 bending cycles. From the results, it is inferred that the prepared films are ideally suitable for food encapsulation and their production on a larger scale can considerably cut down the plastic wastage.


Vibrio parahaemolyticus and related halophilic Vibrios.
Approximately 30 years have elapsed since Dr. Fujino's original discovery that Vibrio parahaemolyticus (then termed Pasteurella parahemolytica) was the cause of "summer diarrhea" in Japan. Since that finding, V. parahaemolyticus has been established as a cause of gastroenteritis in numbers and places approaching global proportions. It has been isolated in marine and estuarine areas almost worldwide and despite its halophilic nature, V. parahaemolyticus has been isolated from saline-free waters. The relationship of this organism to the environment reveals a close association with other marine organisms especially copepods on which the Vibrios depend for survival in winter months and growth in summer months. There is a uniquely provocative disparity between human strains of V. parahaemolyticus which are Kanagawa phenomenon (KP) positive and the environmental strains which to a large extent are KP negative, the significance being that pathogenicity is measured according to the Kanagawa phenomenon (hemolytic activity) reaction. The hemolysin of the pathogenic strains is a thermostable, cardiotoxic protein, which thus far has not been implicated in the mechanism(s) which causes human gastroenteritis. The interest in this organism has been widened in recent years by the finding that similar organisms, V. alginolyticus, lactose positive vibrios and group F vibrios also cause serious disease in humans.


Langerhans cell histiocytosis in a child while in remission for acute lymphocytic leukemia.
The occurrence of Langerhans cell histiocytosis (LCH) and malignancy in the same patient is rare. When LCH occurs concomitantly with acute leukemia, distinct temporal patterns often exist; acute myelogenous leukemia (AML) typically succeeds LCH, whereas acute lymphocytic leukemia (ALL) usually precedes it. We report a case of LCH developing in a child while in remission for ALL. Unique features of this case include the disseminated nature of the LCH and the death of the patient from LCH rather than ALL.


Alendronate therapy in polyostotic fibrous dysplasia presenting with pathologic fracture.
Polyostotic fibrous dysplasia (PFD) is characterized by developmental failure in the remodeling of primitive bone to mature lamellar bone. PFD presents with bone pain, increased bone fragility, deformities, and fractures. Bisphosphonates are the only agents available for medical management.1,2 Intravenous (IV) pamidronate is the established treatment for symptomatic bone involvement in PFD.3,4 Oral alendronate holds promise because of its comparable outcomes, lower cost, and ease of administration.5 The patient described in this case report provided written informed consent for its print and electronic publication after reviewing the complete manuscript and skeletal radiographic images.