Cushing'S syndrome attributable to topical use of lotrisone.
To emphasize the potentially devastating consequences of topical application of corticosteroids. A case report is presented of a previously healthy 38-year-old woman in whom florid Cushing's syndrome developed after prolonged use of Lotrisone. Four years of continuous topical administration of Lotrisone, a combination antifungal-corticosteroid product, led to the development of Cushing's syndrome. The cream had been applied to less than 10% of the total body surface area without use of occlusive dressings, and the patient had no evidence of liver dysfunction or systemic skin disorder. Laboratory studies revealed an unmeasurable corticotropin level, suppressed or unmeasurable cortisol levels, and suppressed or low-normal 24-hour urine collection values for 17-hydroxy-steroids, 17-ketosteroids, and urinary free cortisol, all of which confirm suppression of the hypothalamic-pituitary-adrenal axis. (1) Betamethasone dipropionate can lead to the development of Cushing's syndrome, even in the absence of enhancing factors. (2) Combination medications can lead to the unintentional use of component agents. (3) Availability of potent corticosteroids as over-the-counter medications allows for inappropriate duration of therapy and inadequate medical supervision.


The third space for endoscopic treatment of motility disorders of the gastrointestinal tract.
Over the last few decades, we have seen the further advancement and progress of the field of interventional and therapeutic endoscopy, bringing us to undiscovered areas of the gut's lumen. The development of peroral endoscopic myotomy (POEM) created a breakthrough in the field of therapeutic endoscopy by bringing us to the so-called "third space," which is an artificially created space in the submucosal layer. The rise of third space endoscopy brought us novel and fundamental aspects into therapeutic endoscopy by paving the way to interventions throughout the gastrointestinal (GI) tract. With the success of POEM, the same third space principles have become the foundation for the development of other third space endoscopic techniques for the management of motility disorders of the GI tract, giving rise to a number of POEM offshoots. Since motility disorders of the GI tract are commonly encountered in clinical practice, the development of third space endoscopic interventions to address these disorders was seemingly timely, providing patients optimal care. In this chapter, we would like to offer a closer look and provide the readers a general overview of POEM and other POEM-based techniques which have been developed for the management of motility disorders of the GI tract.


Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi-centre Australian study.
To describe the treatment regimens, duration of therapy and reasons for disease-modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort. A retrospective non-interventional multi-centre study using Audit4 electronic medical records, with de-identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C-reactive protein [DAS28-CRP]), and reasons for treatment cessation were recorded. A total of 3422 rheumatologist-diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28-CRP results (n = 494), the highest mean DAS28-CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%). Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28-CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy.


Barbiturate mortality as an index barbiturate use, Canada, 1950-1963.
Changes in Canadian rates of mortality from barbiturates are examined, and their relation to barbiturate use in the general population is discussed. While the number of deaths attributed to barbiturates quadrupled, from 63 in 1950 to 232 in 1963, there has been a concomitant decrease in the number of deaths from inhalation of utility gas.Combined rates for deaths from utility gas and barbiturates declined steadily for most age groups between 1950-52, 1955-57, and 1959-63. It is possible that the increased mortality from barbiturates represents a change in fashion in regard to method of suicide. Changed mortality from barbiturates is not a valid measure of the extent to which consumption of barbiturates has increased in the Canadian population.


Clinic and Home-Based Exercise with Blood Flow Restriction Resolves Thigh Muscle Atrophy after Anterior Cruciate Ligament Reconstruction with the Bone-Patellar Tendon-Bone Autograft: A Case Report.
Anterior cruciate ligament reconstruction (ACLR) results in thigh muscle atrophy. Of the various interventions proposed to mitigate thigh muscle atrophy, exercise with blood flow restriction (BFR) appears safe and effective. Some literature suggests daily exposure to exercise with BFR may be indicated during the early phase of ACLR rehabilitation; this case report outlines the methodology utilized to prescribe clinic- and home-based BFR within an outpatient rehabilitation program. A 15-year-old male soccer player suffered a left knee injury involving the anterior cruciate ligament and both menisci. He underwent ACLR and completed exercise with BFR as part of his clinic- and home-based rehabilitation program, which included practical blood flow restriction during home-based rehabilitation. After 16 weeks of rehabilitation, surgical limb thigh girth values were objectively larger than the non-surgical limb (surgical, 52.25 cm; non-surgical 50 cm), as well as the multi-frequency bioelectrical impedance analysis of his lower-extremity lean body mass (surgical limb, 10.37 kg; non-surgical limb, 10.02 kg). The findings of this case report suggest that the inclusion of clinic- and home-based BFR within an outpatient rehabilitation program may be indicated to resolve thigh muscle atrophy early after ACLR.


Depressive and anxiety disorders in women with HIV infection.
This study examined whether there were differences in the rate of depressive and anxiety disorders between HIV-infected women (N=93) and a comparison group of uninfected women (N=62). Secondary objectives were to examine correlates of depression in HIV-infected women-including HIV disease stage and protease inhibitor use-and the associations between symptoms of depression or anxiety and other potential predictor variables. Subjects underwent extensive semiannual clinical, psychiatric, neuropsychological, and immunological evaluations. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. Symptoms of depression and anxiety were evaluated with the Hamilton Depression Rating Scale (the 17-item version and a modified 11-item version) and the Hamilton Anxiety Rating Scale, respectively. The rate of current major depressive disorder was four times higher in HIV-seropositive women (19.4%) than in HIV-seronegative women (4.8%). Mean depressive symptom scores on the 17-item Hamilton depression scale also were significantly higher, overall, in the HIV-infected women (mean=8.7, SD=8.0) relative to comparison subjects (mean=3.3, SD=5.8). There was no significant between-group difference in the rate of anxiety disorders. However, HIV-seropositive women had significantly higher anxiety symptom scores (mean=8.8, SD=8.9) than did HIV-seronegative women (mean=3.6, SD=5.5). Both groups had similar substance abuse/dependence histories, but adjusting for this factor had little impact on the relationship of HIV status to current major depressive disorder. HIV-seropositive women without current substance abuse exhibited a significantly higher rate of major depressive disorder and more symptoms of depression and anxiety than did a group of HIV-seronegative women with similar demographic characteristics. These controlled, clinical findings extend recent epidemiologic findings and underscore the importance of adequate assessment and treatment of depression and anxiety in HIV-infected women.


Migraine and the risk of incident hypertension among women.
Background Few studies have examined whether migraine is associated with an increased risk of incident hypertension. Methods We performed a prospective cohort study among 29,040 women without hypertension at baseline. Women were classified as having active migraine with aura, active migraine without aura, a past history of migraine, or no history of migraine. Incident hypertension was defined as new physician diagnosis or newly self-reported systolic or diastolic blood pressure ≥140 mmHg or ≥90 mmHg respectively. Cox proportional hazards models were used to evaluate the association between migraine and incident hypertension. Results During a mean follow-up of 12.2 years, 15,176 incident hypertension cases occurred. Compared to those with no history of migraine, women who experience migraine with aura had a 9% increase in their risk of developing hypertension (95% CI: 1.02, 1.18); women who experience migraine without aura had a 21% increase in their risk of developing hypertension (95% CI: 1.14, 1.28); and women with a past history of migraine had a 15% increase in their risk of developing hypertension (95% CI: 1.07, 1.23). Conclusions Women with migraine have a higher relative risk of developing hypertension compared to women without migraine.


Beware of the origin of numbers: Standard scoring of the SF-12 and SF-36 summary measures distorts measurement and score interpretations.
The 12-item Short Form Health Survey (SF-12) is a generic health rating scale developed to reproduce the Physical and Mental Component Summary scores (PCS and MCS, respectively) of a longer survey, the SF-36. The standard PCS/MCS scoring algorithm has been criticized because its expected dimensionality often lacks empirical support, scoring is based on the assumption that physical and mental health are uncorrelated, and because scores on physical health items influence MCS scores, and vice versa. In this paper, we review the standard PCS/MCS scoring algorithm for the SF-12 and consider alternative scoring procedures: the RAND-12 Health Status Inventory (HSI) and raw sum scores. We corroborate that the SF-12 reproduces SF-36 scores but also inherits its problems. In simulations, good physical health scores reduce mental health scores, and vice versa. This may explain results of clinical studies in which, for example, poor physical health scores result in good MCS scores despite compromised mental health. When applied to empirical data from people with Parkinson's disease (PD) and stroke, standard SF-12 scores suggest a weak correlation between physical and mental health (rs .16), whereas RAND-12 HSI and raw sum scores show a much stronger correlation (rs .67-.68). Furthermore, standard PCS scores yield a different statistical conclusion regarding the association between physical health and age than do RAND-12 HSI and raw sum scores. We recommend that the standard SF-12 scoring algorithm be abandoned in favor of alternatives that provide more valid representations of physical and mental health, of which raw sum scores appear the simplest.


Orthogonal spin labeling and Gd(III)-nitroxide distance measurements on bacteriophage T4-lysozyme.
We present the first example of chemoselective site-specific spin labeling of a monomeric protein with two spectroscopically orthogonal spin labels: a gadolinium(III) chelate complex and a nitroxide radical. A detailed analysis of the performance of two commercially available Gd(III) ligands in the Gd(III)-nitroxide pulse double electron-electron resonance (DEER or PELDOR) experiment is reported. A modification of the flip angle of the pump pulse in the Gd(III)-nitroxide DEER experiment is proposed to optimize sensitivity.


Successful application of preimplantation genetic diagnosis for beta-thalassaemia and sickle cell anaemia in Italy.
In Italy, the autosomal recessive diseases beta-thalassaemia and sickle cell anaemia are so widespread that in some regions they can be defined as 'social diseases'. In this study, nine clinical applications of preimplantation genetic diagnosis (PGD) were performed for beta-thalassaemia and sickle cell anaemia on seven Sicilian couples and carriers of beta-globin gene mutations. The studied mutations were: Cd39, HbS, IVS1 nt1, IVS1 nt6 and IVS1 nt110. ICSI was performed with partner's sperm on 131 out of 147 retrieved oocytes, and this resulted in 72 zygotes; 32 embryos were successfully biopsied on day 3. The biopsied blastomeres were lysed and the beta-globin alleles amplified by nested PCR. The mutation diagnosis was performed by restriction enzyme digestion and reverse dot-blot. The amplification efficacy was 97.2%. The genotype study of non-transferred and surplus embryos showed that the allele drop-out rate was 8.6%. Seventeen embryos were transferred in utero on day 4. All couples received an embryo transfer; of the four pregnancies obtained, three resulted in live births and one miscarried at 11 weeks. Prenatal diagnosis at the 11th week and miscarriage material analysis confirmed the PGD results. These studies represent the first successful application of PGD for beta-thalassaemia and sickle cell anaemia in Italy.


A systematic literature review on the humanistic burden of cytomegalovirus.
Cytomegalovirus (CMV) infection is typically asymptomatic in healthy individuals; however, certain populations are vulnerable to infection and may develop serious sequelae. CMV infection may also have a broad impact on humanistic outcomes, including patient health status and quality of life (QoL). We conducted a systematic literature review (SLR) to describe the global humanistic burden of CMV and congenital CMV (cCMV) infections across all age groups. Medline, Embase, and LILACS were searched to identify studies on humanistic outcomes following CMV infection, including health status/QoL and any outcomes in domains such as auditory performance, cognitive ability, developmental status, intelligence, language, memory, mental health, motor performance, social communication, speech, and vocabulary. The SLR included articles published from 2000 to 2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America, and North America. Sixty-three studies met the inclusion criteria. In general, individuals with symptomatic cCMV infection experience a greater burden of disease and more substantial impact on QoL versus those with asymptomatic cCMV infection. Children with hearing loss due to cCMV infection, both symptomatic and asymptomatic, showed improved auditory outcomes following cochlear implantation. Newborns, infants, and children with cCMV infections had worse cognitive outcomes in psychological development, sequential and simultaneous processing, phonological working memory, and attention control versus age-matched controls without cCMV infection. CMV infection was also associated with cognitive decline in elderly populations. CMV infection can have substantial, lifelong, heterogenous impacts on humanistic outcomes, including health status and QoL, which should be considered when developing and implementing treatment and prevention strategies.


On the importance of geometric nonlinearity in finite-element simulations of trabecular bone failure.
The finite element method, which has been successfully applied to studies of the elastic properties of trabecular bone, is now being used to simulate its failure. These simulations have used a geometrically linear (linear kinematic) approximation to the total stiffness matrix; nonlinear terms in the total stiffness matrix have been excluded from the computation in order to achieve efficiency. Because trabecular bone appears to be a slender (i.e., geometrically nonlinear) structure, we studied the validity of the linear kinematic approximation for simulating its failure. Two cases, designed to bracket the extremes of stability behavior, were explored: a single representative spicule of trabecular bone (case 1) and a volume of trabecular bone consisting of relatively low aspect ratio members (case 2). For case 1, geometrically linear (GL) and nonlinear (GNL) analyses were performed with two different materials models: a plastic damage model and a brittle damage model. When GNL terms were included in the total stiffness matrix, we found that load-path bifurcation preceded tissue failure regardless of the form of the damage model. This bifurcation was the result of a complex coupling between material yield and structural instability. The nature of this coupling was highly sensitive to the form of the damage model. None of these behaviors was observed in the linear analyses, where failure was insensitive to the form of the damage model and where structural instabilities were prevented from occurring. For case 2, compressive loading of a volume of trabecular bone, geometric nonlinear effects were pronounced. There was a bifurcation in load response that resulted in large apparent strain to failure. The GL simulations, on the other hand, precluded this bifurcation. We hypothesize that trabecular bone is a geometric nonlinear structure; nonlinear terms must be included in the total stiffness matrix to accurately simulate its failure.


Investigation of the correlation between some immune system and biochemical indicators in patients with type 2 diabetes.
Since changes in some immune system indicators such as leukocyte count and neutrophil to lymphocyte ratio in the blood and Inflammation is directly in relation with the pathogenesis of type 2 diabetes, metabolic syndrome and atherosclerosis, measuring these indicators in patients with type 2 diabetes and comparing them with control group can be a suitable indicator of Inflammation and prognosis of the disease. The current study was done on 75 patients with type 2 diabetes and 72 healthy individuals as patient and healthy group respectively. The selected groups have been matched for age and sex. Fasting blood sugar, lipid profile including triglycerides, total cholesterol, HDL, LDL, as well as the number of white blood cells, neutrophils, lymphocytes, neutrophils to lymphocytes ratio were measured and analyzed in both groups. The results demonstrated that there is a significant relationship between the number of white blood cells and increase in blood sugar and also between the neutrophil to lymphocyte ratio and increase in Fasting blood sugar and triglycerides parameters. Furthermore, the average of fasting blood sugar, triglycerides, total cholesterol, LDL and neutrophil to lymphocyte ratio in patient with type 2 diabetes is significantly higher than control group. Considering the findings of current study, we showed the inflammation and the pathogenesis caused by type 2 diabetes can be attributed to neutrophil to lymphocyte ratio.


The Challenges of Transition From Donor-Funded Programs: Results From a Theory-Driven Multi-Country Comparative Case Study of Programs in Eastern Europe and Central Asia Supported by the Global Fund.
In the era of declining development assistance for health, transitioning externally funded programs to governments becomes a priority for donors. However, the process requires a careful approach not only to preserve the public health gains that have already been achieved but also to expand on them. In the Eastern Europe and Central Asia region, countries are expected to graduate from support from the Global Fund to Fight AIDS, Tuberculosis and Malaria in or before 2025. We aim to describe transition risks and identify possible means to address them. Using a theory-based conceptual framework-Transition Preparedness Assessment of Tuberculosis and HIV/AIDS programs-we investigated transition-related challenges through a health systems lens in 10 countries of the Eastern Europe and Central Asia region during 2015-2017. Study findings were derived from systematic collection of quantitative data on socioeconomic indicators and disease epidemics as well as qualitative data from in-depth interviews with 264 stakeholders. These findings were then compared with other donor transition experiences documented elsewhere. We found numerous common transition challenges, such as poor monitoring of a country's macroeconomic performance along with weakness in estimating financial needs for successful transition; limited political will of governments to replace donor-funded programs; punitive legislation criminalizing certain behaviors and constraining the government's ability to allocate funds and contract civil society organizations essential to providing services for key populations; limited coordination function of governments and weak decision-making power of coordinating mechanisms obscuring the latter's future role; and inadequate function of national procurement and supply chain management systems undermining an uninterrupted supply of quality-assured drugs and commodities. These challenges are compounded by the risks related to health workforce management leading to specialist shortages and/or inadequately skilled and qualified professionals and by limited funding for critical surveillance activities. The complex and multidimensional transition process requires a multipronged approach through well-planned collective and coordinated responses from global, bilateral, and national partners in coming years. Other similar transition processes may provide guidance. Although no "one-size-fits-all" approach exists, previous experiences highlight a need for both early planning and monitoring of the transition along several key dimensions. Issues that could threaten the maintenance of health gains include ongoing stigma against key populations; continued heavy reliance on external funding in some countries, especially for preventive services; the institutional viability of the country coordinating mechanisms; and emerging difficulties with procurement of quality drugs at reasonable prices.


Annual Rite of Spring
Some consider spring the preparation for summer, a dress rehearsal for the primary season of high expectations to recharge. But spring for oncology nurses means coming together at the annual Oncology Nursing Society Congress.


Identification of altered metabolic functional components using metabolomics to analyze the different ages of fruiting bodies of Sanghuangporus vaninii cultivated on cut log substrates.
Sanghuangporus vaninii is a profitable traditional and medicinal edible fungus with uncommon therapeutic properties and medicinal value. The accumulation of active ingredients in this fungus that is used in traditional Chinese medicine is affected by its years of growth, and their pharmacological activities are also affected. However, the effects of age on the medicinal value of fruiting bodies of S. vaninii cultivated on cut log substrate remain unclear. In this study, an untargeted liquid chromatography mass spectrometry (LC-MS)-based metabolomics approach was performed to characterize the profiles of metabolites from 1-, 2- and 3-year-old fruiting bodies of S. vaninii. A total of, 156 differentially accumulated metabolites (DAMs) were screened based on the criterion of a variable importance projection greater than 1.0 and p < 0.01, including 75% up regulated and 25% down regulated. The results of enrichment of metabolic pathways showed that the metabolites involved the biosynthesis of plant secondary metabolites, biosynthesis of amino acids, central carbon metabolism in cancer, steroid hormone biosynthesis, linoleic acid metabolism, prolactin signaling pathway, and arginine biosynthesis, and so on. The biosynthesis of plant secondary metabolites pathway was significantly activated. Five metabolites were significantly elevated within the growth of fruiting bodies, including 15-keto-prostaglandin F2a, (4S, 5R)-4,5,6-trihydroxy-2-iminohexanoate, adenylsuccinic acid, piplartine, and chenodeoxycholic acid. 15-keto-prostaglandin F2a is related to the pathway of arachidonic acid metabolism and was significantly increased up to 1,320- and 535-fold in the 2- and 3-year-old fruiting bodies, respectively, compared with those in the 1-year-old group. The presence of these bioactive natural products in S. vaninii is consistent with the traditional use of Sanghuang, which prompted an exploration of its use as a source of natural prostaglandin in the form of foods and nutraceuticals. These findings may provide insight into the functional components of S. vaninii to develop therapeutic strategies.


[Reconstruction of large foot sole areas with microsurgical tissue transfers].
In 14 patients with microsurgically reconstructed areas of the sole videografic gait analysis was performed. The best results are reached after reconstruction of the forefoot. Loss of more than two thirds of the sole leads to functional impairment. For all reconstructed areas and all types of flaps gait is improved significantly by shoe adaptation: elevation of the shoe under the reconstructed part of the sole directs the main load to the opposite side of the foot and by this relieves the reconstructed area. Even bone corrections can reduce load on a circumscribed area.


[Gastritis. Current point of view of the anatomo-pathologist].
Acute, granulomatous and chronic are the three main forms of gastritis. The discovery of Helicobacter pylori has stimulated a new detailed classification of gastritis. Having set out the various conventional histopathological classifications, the authors describe two newly recognized types of gastritis, lymphocytic gastritis and reactive gastritis. The authors also recall the earlier pathogenic classifications of gastritis, first initiated by Strickland and Mackay. Because of the problems related to these earlier classifications, the "Sydney system" has been developed. This system allows to simply pathologists' reports, by incorporating the morphological, topographical and etiological parameters of gastritis. Some of the advantages and disadvantages of the "Sydney system" are briefly discussed.


Localization, specific activity, and molecular forms of acetylcholinesterase in developmental stages of the cestode Mesocestoides corti.
The nervous system of flatworms is quite simple although there is increasing evidence indicating that it is chemically complex. Studies of the nervous system in these animals have only been performed in the larval stage or in the adult worms, which are easy to obtain in nature, while the description of the nervous system in developing stages of these organisms is missing. Mesocestoides corti is a parasitic platyhelminth whose larvae can be induced in vitro to develop to adult, sexually mature worms, opening the possibility of studying the nervous system of a flatworm in different stages of development. Here, we describe the presence, activity, location, and molecular forms of acetylcholinesterase (AChE) in different stages of development of M. corti, from the larvae to adult forms of this endoparasite, obtained in in vitro cultures after induction of the larval stage with trypsin. Our results point to AChE as a molecular marker of the nervous system in platyhelminthes. The change in molecular forms of this enzyme and the increase in its activity during development from larvae to adult worm may reflect the presence of a more complex nervous system, necessary to adjust and coordinate the movement of a much bigger structure. A relationship between the development of the reproductive apparatus in segmented and adult worms with a more complex nervous system in these stages is also apparent. Finally, our study opens the possibility of applying anti-AChE as more effective therapeutic strategies against cestode parasites.


Associations Among Hip Structure, Bone Mineral Density, and Strength Vary With External Bone Size in White Women.
Bone mineral density (BMD) is heavily relied upon to reflect structural changes affecting hip strength and fracture risk. Strong correlations between BMD and strength are needed to provide confidence that structural changes are reflected in BMD and, in turn, strength. This study investigated how variation in bone structure gives rise to variation in BMD and strength and tested whether these associations differ with external bone size. Cadaveric proximal femurs (n = 30, White women, 36-89+ years) were imaged using nanocomputed tomography (nano-CT) and loaded in a sideways fall configuration to assess bone strength and brittleness. Bone voxels within the nano-CT images were projected onto a plane to create pseudo dual-energy X-ray absorptiometry (pseudo-DXA) images consistent with a clinical DXA scan. A validation study using 19 samples confirmed pseudo-DXA measures correlated significantly with those measured from a commercially available DXA system, including bone mineral content (BMC) (R 2 = 0.95), area (R 2 = 0.58), and BMD (R 2 = 0.92). BMD-strength associations were conducted using multivariate linear regression analyses with the samples divided into narrow and wide groups by pseudo-DXA area. Nearly 80% of the variation in strength was explained by age, body weight, and pseudo-DXA BMD for the narrow subgroup. Including additional structural or density distribution information in regression models only modestly improved the correlations. In contrast, age, body weight, and pseudo-DXA BMD explained only half of the variation in strength for the wide subgroup. Including bone density distribution or structural details did not improve the correlations, but including post-yield deflection (PYD), a measure of bone material brittleness, did increase the coefficient of determination to more than 70% for the wide subgroup. This outcome suggested material level effects play an important role in the strength of wide femoral necks. Thus, the associations among structure, BMD, and strength differed with external bone size, providing evidence that structure-function relationships may be improved by judiciously sorting study cohorts into subgroups. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Effect of Genetics, Environment, and Phenotype on the Metabolome of Maize Hybrids Using GC/MS and LC/MS.
We evaluated the variability of metabolites in various maize hybrids due to the effect of environment, genotype, phenotype as well as the interaction of the first two factors. We analyzed 480 forage and the same number of grain samples from 21 genetically diverse non-GM Pioneer brand maize hybrids, including some with drought tolerance and viral resistance phenotypes, grown at eight North American locations. As complementary platforms, both GC/MS and LC/MS were utilized to detect a wide diversity of metabolites. GC/MS revealed 166 and 137 metabolites in forage and grain samples, respectively, while LC/MS captured 1341 and 635 metabolites in forage and grain samples, respectively. Univariate and multivariate analyses were utilized to investigate the response of the maize metabolome to the environment, genotype, phenotype, and their interaction. Based on combined percentages from GC/MS and LC/MS datasets, the environment affected 36% to 84% of forage metabolites, while less than 7% were affected by genotype. The environment affected 12% to 90% of grain metabolites, whereas less than 27% were affected by genotype. Less than 10% and 11% of the metabolites were affected by phenotype in forage and grain, respectively. Unsupervised PCA and HCA analyses revealed similar trends, i.e., environmental effect was much stronger than genotype or phenotype effects. On the basis of comparisons of disease tolerant and disease susceptible hybrids, neither forage nor grain samples originating from different locations showed obvious phenotype effects. Our findings demonstrate that the combination of GC/MS and LC/MS based metabolite profiling followed by broad statistical analysis is an effective approach to identify the relative impact of environmental, genetic and phenotypic effects on the forage and grain composition of maize hybrids.


Effect of elastin-like polypeptide incorporation on the adhesion maturation of mineral trioxide aggregates.
The aim of this study was to investigate the effects of the incorporation of elastin-like polypeptide (ELP) on the adhesion maturation of mineral trioxide aggregates (MTA). Two types of ELPs (V125 and V125E8) were genetically synthesized. V125 consisted of 125 repeating pentapeptides (Val-Pro-Gly-Xaa-Gly) and V125E8 was functionalized with octaglutamic acid in the C-terminus of V125; both were diluted to 10 wt% in solution. Three 1.5 mm diameter holes in dentin discs were filled with MTA mixed with either a solution of ELP or deionized water. Push-out bond strength tests were performed following storage in simulated body fluid (SBF) for 1, 2, 4, and 8 weeks (n = 12). The interface between dentin and MTA was observed via scanning electron microscopy (SEM). The maturation of MTA was evaluated with a stereoscopic microscope and SEM. The incorporation of a specific ELP (V125E8) significantly increased the bond strength of MTA to dentin with regard to every maturation period (p < 0.05). The bond strength of MTA also significantly increased with a longer maturation time irrespective of ELP incorporation (p < 0.05). V125E8-incorporated MTA exhibited a more intimate interface with dentin compared to the other groups. More spindle-shaped crystal structures and thicker crystals were observed in all MTA mixtures as the storage duration increased even though V125E8 exhibited fewer crystal structures on the surface. Within the limitations of this study, the incorporation of V125E8 increased the adhesive properties of MTA and the maturation of MTA occurred regardless of ELP incorporation.


Analysis of differentiation and transformation of cells by lectins.
During differentiation cells are known to change their biological behavior according to their genotype. This is thought to be accompanied by a modulation of cell surface determinants expressed on the outer cell membrane. Vice versa, cell surface molecules are suggested to mediate extracellular signals to the genome. Most of these molecules integrated in the cell membrane have been proven to be glycoconjugates. The carbohydrate moieties of these molecules can be detected by means of lectins that are characterized by their ability to react specifically with distinct terminal sugar sequences. Thus, lectins have been used as appropriate tools for studying the modulation of functionally important membrane-associated molecules during the differentiation of cells, in particular of B- and T-lymphocytes. Moreover, lectins have been proven to distinguish between differentiated cells and malignant cell clones, according to the hypothesis that transformed cells possess a glycoconjugate profile that corresponds to the stage of differentiation at which they are arrested. Since lectins, like monoclonal antibodies, make it possible to study functionally important molecules that are associated with differentiation and malignancy, they might be of value for diagnostic purposes and, moreover, for analyzing malignant transformation.


Global calculation of nuclear shape isomers.
To determine which nuclei may exhibit shape isomerism, we use a well-benchmarked macroscopic-microscopic model to calculate potential-energy surfaces as functions of spheroidal (epsilon{2}), hexadecapole (epsilon{4}), and axial-asymmetry (gamma) shape coordinates for 7206 nuclei from A=31 to A=290. We analyze these and identify the deformations and energies of all minima deeper than 0.2 MeV. These minima may correspond to characteristic experimentally observable shape-isomeric states. Shape isomers mainly occur in the A=80 region, the A=100 region, and in an extended region centered around (208)Pb. We compare our model to experimental results for Kr isotopes. Moreover, in a plot versus N and Z we show for each of the 7206 nuclei the calculated number of minima. The results reveal one fairly unexplored region of shape isomerism, which is experimentally accessible, namely the region northeast of (82)(208)Pb.


[Occult peritonsillar abscess: an unusual cause of unilateral tonsillar enlargement].
Peritonsillar abscess is a suppurative infection of the tissues adjacent to the palatine tonsil and is regarded in otolarygologic practice as a complication of pharyngotonsillitis. The most common presentation is gradually increasing pain, fever, trismus, drooling and a muffled voice. Asymmetric tonsils are common in clinical practice. Differential diagnosis includes infectious, granulomatous, congenital and neoplastic lesions. This is a case study of two patients evaluated for unilateral tonsillar enlargement who were found to have a previously unexpected peritonsillar abscess at tonsillectomy. The patients had no other signs or symptoms of acute pharyngotonsillar or peritonsillar infection. To our knowledge, this is the first report of an occult peritonsillar infection causing unilateral tonsillar enlargement.


Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice.
Bicyclol, a novel synthetic antihepatitis drug, has been shown to protect against liver injury via various pharmacological activities. The purpose of the current study was to further investigate the protective effect of bicyclol against carbon tetrachloride (CCl4)-induced acute liver injury (ALI) and its underlying molecular mechanism, particularly autophagic machinery, anti-oxidative, and anti-inflammatory potentials. Our results found that treatment with bicyclol significantly reduced CCl4-induced hepatotoxicity by alleviating histopathological liver changes, decreasing the alanine transaminase levels, promoting autophagic flux, attenuating the expression of inflammatory cytokines, and modulating oxidative markers. Furthermore, bicyclol efficiently induced the conversion of LC3 and enhanced the liver expressions of ATG7 and Beclin-1. Meanwhile, bicyclol induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and p62. These protective effects may be mediated by activation of AMP-activated protein kinase and inhibition of mTOR or MAPK signaling pathways. Taken together, our study firstly suggests that bicyclol has protective potential against CCl4-induced hepatotoxicity, which might be closely associated with induction of autophagy, concomitant anti-oxidative stress, and anti-inflammatory response.


A pectinmethylesterase gene associated with a heat-stable extract from citrus.
A putative thermostable pectinmethylesterase (TSPME) protein of 36 kDa was isolated from heat-treated citrus finisher pulp. After purification and partial sequencing of the protein, a reverse genetic approach was used to obtain the complete genomic sequence of a new pectinmethylesterase (PME) gene, CsPME4, from Citrus sinensis (L.) Osb. cv. Valencia. The CsPME4 gene contained two exons of 1203 and 690 bp interrupted by a single positionally conserved intron of 1230 bp. A full-length CsPME4 cDNA clone amplified from Valencia orange juice vesicles shared 98% identity with the genomic clone. The encoded protein of the full-length CsPME4 cDNA shared 66 and 39% amino acid identity with the full-length encoded proteins of the citrus PME, CsPME1, and CsPME3, respectively, whereas the predicted mature protein of CsPME4 shared 80 and 61% identity with the predicted mature proteins of CsPME1 and CsPME3, respectively. Southern analysis demonstrated that CsPME4 was present in at least two copies in the Valencia orange genome. Northern analysis revealed that CsPME4 mRNA was accumulated mainly in young and developing tissues of Valencia orange. Several approaches to express recombinant CsPME4 in different systems failed to obtain active protein. Further research will be necessary to successfully express the putative TSPME gene CsPME4 for biochemical characterization.


Dose-dependent subcutaneous absorption of porcine, bovine and human NPH insulins.
The absorption of 125I-labelled porcine, bovine and human neutral protamine Hagedorn (NPH) insulins was compared in 40 diabetic patients after subcutaneous injections in the thighs using doses of 6 and 24 IU (40 IU/ml). Furthermore, the absorption of porcine NPH insulin was compared with bovine NPH insulin and porcine lente type insulin in the same dose (6 IU). All these intermediately acting insulins showed similar absorption rates when administered in the same dose. However, an increase in the injected dose from 6 to 24 IU resulted in a decrease of approximately 30% in the absorption rate of all NPH insulins.


Development of a stability-indicating RP-LC method for the separation of a critical pair of impurities and their degradants in zafirlukast.
A high-throughput reverse-phase liquid chromatographic (RP-LC) method is developed for the quantification of zafirlukast and its related impurities in drug substance. The separation of known impurities is accomplished using a short (50 mm) LC column with sub-2-µm particle size in a relatively short run-time. A linear gradient elution involves ammonium formate and acetonitrile as mobile phase. The critical impurity pair is the meta and para isomers of zafirlukast, which are known to be potential impurities of zafirlukast, whose resolution is sensitive to pH. The stability-indicating capability of the developed method is demonstrated using forced degradation samples from stress conditions such as hydrolysis, oxidation, thermal and photolytic degradation. The developed RP-LC method is validated in accordance with International Conference on Harmonization requirements. The results from the validation study indicate that this RP-LC method can be used for the determination of synthetic and degradation impurities in regular quality control analysis for the drug substance.


Diffusion and perfusion MRI, measurements of acute stroke events and outcome: present practice and future hope.
The morphological, metabolic and functional changes of brain ischaemia can be studied using various MRI methods. These are readily available should the early visualisation of affected territories be needed. Morphological changes include the depiction of oedema on T1- and T2-weighted images, and metabolic changes are reflected on magnetic resonance spectroscopy. Functional changes reflect haemodynamic failure seen on diffusion- and perfusion-weighted imaging. Modelling of behaviour of T2 and diffusion changes could predict the histological outcome of affected tissue regarding cell recovery on necrosis. In addition, the combination of diffusion and perfusion MRI offers a potential prognostic value.


Role of presynaptic phosphoprotein synapsin II in schizophrenia.
Synapsin II is a member of the neuronal phosphoprotein family. These phosphoproteins are evolutionarily conserved across many organisms and are important in a variety of synaptic functions, including synaptogenesis and the regulation of neurotransmitter release. A number of genome-wide scans, meta-analyses, and genetic susceptibility studies have implicated the synapsin II gene (3p25) in the etiology of schizophrenia (SZ) and other psychiatric disorders. Further studies have found a reduction of synapsin II mRNA and protein in the prefrontal cortex in post-mortem samples from schizophrenic patients. Disruptions in the expression of this gene may cause synaptic dysfunction, which can result in neurotransmitter imbalances, likely contributing to the pathogenesis of SZ. SZ is a costly, debilitating psychiatric illness affecting approximately 1.1% of the world's population, amounting to 51 million people today. The disorder is characterized by positive (hallucinations, paranoia), negative (social withdrawal, lack of motivation), and cognitive (memory impairments, attention deficits) symptoms. This review provides a comprehensive summary of the structure, function, and involvement of the synapsin family, specifically synapsin II, in the pathophysiology of SZ and possible target for therapeutic intervention/implications.


Mechanical Properties and Deformation Mechanisms of Nanocrystalline U-10Mo Alloys by Molecular Dynamics Simulation.
U-Mo alloys were considered to be the most promising candidates for high-density nuclear fuel. The uniaxial tensile behavior of nanocrystalline U-10Mo alloys with average grain sizes of 8-23 nm was systematically studied by molecular dynamics (MD) simulation, mainly focusing on the influence of average grain size on the mechanical properties and deformation mechanisms. The results show that Young's modulus, yield strength and ultimate tensile strength follow as average grain size increases. During the deformation process, localized phase transitions were observed in samples. Grain boundary sliding and grain rotation, as well as twinning, dominated the deformation in the smaller and larger grain sizes samples, respectively. Increased grain size led to greater localized shear deformation, resulting in greater stress drop. Additionally, we elucidated the effects of temperature and strain rate on tensile behavior and found that lower temperatures and higher strain rates not only facilitated the twinning tendency but also favored the occurrence of phase transitions in samples. Results from this research could provide guidance for the design and optimization of U-10Mo alloys materials.


Factors associated with the development of asthma and hay fever in children: the possible risks of hospitalization, surgery, and anesthesia.
The clinical impression of an allergist that early surgery increases the risk for developing asthma or hayfever was followed up by three studies. First, 115 children with pyloric stenosis were followed up and showed above-average prevalence figures. Second, 47 boys with hernia repairs were followed with similar results. Thirdly, 202 children reporting asthma or hay fever were studied for early hospitalizations. They reported more hospitalizations under the age of 2 than did a control group.


Ferrochelatase of spinach chloroplasts.
Spinach chloroplasts catalyse the incorporation of Fe(2+) into protoporphyrin, mesoporphyrin and deuteroporphyrin to form the corresponding haems. This ferrochelatase activity was detected by pyridine haemochrome formation with acetone-dried powders of chloroplasts, or from the formation of [(59)Fe]haems by intact chloroplasts. Decreasing the mitochondrial contamination of the chloroplasts by density-gradient centrifugation did not cause any loss of activity: spinach ferrochelatase appears to be principally a chloroplast enzyme. The characteristics of the enzyme were examined by using [(59)Fe]haem assay. The activity was pH-dependent: for both mesohaem and protohaem formation there were two pH maxima, a major peak at about pH7.8 and a smaller peak at about pH9.2. Lineweaver-Burk plots showed that the K(m) for Fe(2+) incorporation into protoporphyrin was 8mum and that for Fe(2+) incorporation into mesoporphyrin was 36mum. At non-saturating Fe(2+) concentrations the K(m) for protoporphyrin was 0.2mum and that for mesoporphyrin was 0.4mum. Ferrochelatase was not solubilized by treatment of chloroplasts with ultrasound but was solubilized by stirring in 1% (w/v) Tween 20 at pH10.4. Unlike the rat liver mitochondrial enzyme, chloroplast ferrochelatase was not stimulated by treatment with selected organic solvents. The spinach enzyme was inactive in aerobic conditions and it was shown by using an oxygen electrode that under such conditions the addition of Fe(2+) to buffer solutions caused a rapid uptake of dissolved oxygen, believed to be due to the oxidation of Fe(2+) to Fe(3+); Fe(3+) is not a substrate for ferrochelatase.


[Evaluation of current guidelines for flying capacity and internationally proposed revisions].
Despite several modifications of medical requirements for German flight personnel, these requirements have often been criticized by ophthalmologists because of their margins of interpretation. In many controversial cases regarding pilot licences, the final decision has to be made by the national aeromedical review board. The progress in ophthalmologic microsurgery, e.g. intraocular lens implantation and refractive surgery, has led to a certain insecurity among surgeons as to how to deal with these developments within the requirements. Besides, new cockpit designs with multiple colour displays have changed the demands on the pilot's visual system, especially with regard to colour perception. New European requirements which will probably become effective in 1994 are compared to the existing German standards.


Effects of estrogen deficiency on tooth movement after force application: an experimental study in ovariectomized rats.
The aim of this study was to investigate the effects of estrogen deficiency on tooth movement in ovariectomized rats. Forty-two adult female Sprague-Dawley rats were assigned at random to one of the following groups: test group (n=20), ovariectomized rats (or estrogen-deficient rats); control group (n=22), non-ovariectomized rats. Two months after ovariectomy, expansion springs exerting 10 g of force were inserted between the upper central incisors in both groups. The amount of movement was measured daily until tooth movement began and then at intervals of 3 days. The rats were sacrificed 18 days after applying the expansion spring and histomorphometric analysis was performed along the left upper central incisor root towards the apex of the alveolar bone. The amount and speed of movement was observed to be greater in ovariectomized rats. On histomorphometric analysis, osteoblast and osteocyte counts on the pressure side were higher in the non-ovariectomized group than in the ovariectomized group (p<0.001). In contrast, the osteoclast count was significantly higher (p<0.01) in the ovariectomized group than in the non-ovariectomized group. The osteoblast and osteocyte counts were significantly higher (p<0.001) on tension side in the non-ovariectomized group than in the ovariectomized group. Estrogen deficiency increased orthodontic tooth movements but counts of osteoblasts, which are responsible for new bone formation, were lower in regions of tension and of pressure.


Optimization of liquid fertilizer production from waste seaweed: A design of experiment based statistical approach.
In Istanbul, which is surrounded by the sea on 3 sides, thousands of tons of seaweed that have formed naturally every year are washed ashore. In this study, the usability of these seaweeds which are landfilling already in fertilizer production was discussed. Liquid fertilizer production was carried out using 3 different physical and 4 different biological methods, and the produced fertilizers were diluted in 5 different ratios (1%, 10%, 25%, 50%, and 100%) and applied to cress seed. The effect of each fertilizer and its concentration on seed germination, plant length, number of leaves, and soil moisture-holding capacity was studied. The data obtained were analyzed using Response Surface Methodology (RSM). The results showed that if seaweed was fermented with anaerobic seed sludge for 15 days and applied to the plant by diluting it to 15-25%, plant growth will be supported at an optimum level. It has also been shown that if the seaweed was fermented with yeast culture for 18 days and fed with a concentration of >90%, the moisture-holding capacity of the soil could be increased by up to 27%.


Cycloaddition Reactions of Cobalt-Complexed Macrocyclic Alkynes: The Transannular Pauson-Khand Reaction.
The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2 + 2 + 1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Macrocyclic enyne and dienyne complexes were readily synthesized by palladium(II)-catalyzed oxidative macrocyclizations of bis(vinyl boronate esters) or ring-closing metathesis reactions followed by complexation with dicobalt octacarbonyl. Several reaction modalities of these macrocyclic complexes were uncovered. In addition to the first successful transannular Pauson-Khand reactions, other intermolecular and transannular cycloaddition reactions included intermolecular Pauson-Khand reactions, transannular [4 + 2] cycloaddition reactions, intermolecular [2 + 2 + 2] cycloaddition reactions, and intermolecular [2 + 2 + 1 + 1] cycloaddition reactions. The structural and reaction requirements for each process are presented.


Digestive Ripening: A Fine Chemical Machining Process on the Nanoscale.
A comprehensive overview of the process of digestive ripening that is known to convert polydisperse nanocrystals to monodisperse ones is presented. Apart from highlighting the role of organic molecules (ligands) in achieving size control, the roles of other parameters such as the nanocrystal-ligand binding strength and the temperature at which the reaction is carried out in accomplishing size control are also delineated. The generality of the procedure is illustrated by providing examples of how it is used to prepare monodisperse nanocrystals of different metals, alloy systems, and ultrasmall nanocrystals and also to narrow the size distribution in complex binary and ternary nanocrystal systems. Finally, the current status as far as the theoretical understanding of how size control is being achieved by digestive ripening is laid out, emphasizing at the same time the necessity to undertake more systematic studies to completely realize the full potential of this practically very useful procedure.


Celastrol aggravates LPS-induced inflammation and injuries of liver and kidney in mice.
Sepsis, a life-threatening syndrome with uncontrolled inflammatory response, causes high morbidity and mortality worldwide. Currently, satisfactory treatments on sepsis are still lacking in clinic. Thus, new therapeutic strategies are urgently required. Recently, celastrol, a pentacyclic triterpene extracted from the traditional Chinese medicine Tripterygium Wilfordi plant, attracted great interest for its properties of anti-inflammation, anti-oxidative stress, and metabolism remodeling. However, the effect of celastrol on sepsis is still unclear. In this study, we investigated the effect of celastrol on lipopolysaccharides (LPS)-induced inflammation and organ injuries in mice. Following celastrol pretreatment, mice showed increased mortality rate and aggravated inflammation evidenced by further enhanced inflammatory markers of IL-6, IL-1β, TNF-α, IL-18, MCP-1, and ICAM-1 in circulation, liver, and kidney after LPS treatment. The serum levels of ALT, AST, and LDH were further increased in parallel with the deteriorated liver morphological damage (H&E) and oxidative stress in celastrol-treated mice, indicating an aggravated liver injury. In kidney, the expressions of tubular injury markers of kidney injury molecule-1 (KIM-1) and gelatinase-associated lipocalin (NGAL) were further upregulated along with higher levels of blood urea nitrogen (BUN), creatinine (Cr), and MDA in celastrol-treated mice. These findings not only indicated a detrimental role of celastrol therapy in LPS-induced inflammation and organ injuries but also suggested the restriction of celastrol usage in sepsis patients.


Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis.
Biallelic mutations in the base excision DNA repair gene MUTYH lead to MUTYH-associated polyposis (MAP) and predisposition to colorectal cancer (CRC). Functional studies have demonstrated significant differences in base recognition and glycosylase activity between various MUTYH mutations, notably for the 2 mutations most frequently reported in MAP patients: Y179C and G396D (previously annotated as Y165C and G382D). Our goal was to establish correlations between genotypes and colorectal phenotype of patients with MAP. In this multicenter study, we analyzed genotype and phenotype data from 257 MAP patients. Data included age at presentation of MAP, polyp count, and the occurrence, location, and age at presentation of CRC. Patients with a homozygous G396D mutation or compound heterozygous G396D/Y179C mutations presented later with MAP and had a significantly lower hazard of developing CRC than patients with a homozygous Y179C mutation (P < .001). The mean ages of CRC diagnosis in patients were 58 years (homozygous G396D) and 52 years (compound heterozygous G396D/Y179C) versus 46 years (homozygous Y179C; P = .001, linear regression). Our study identified the phenotypic effects of Y179C as relatively severe and of G396D as relatively mild. These clinical data are in accord with findings from in vitro functional assays. Genotypic stratification may become useful in the development of guidelines for counseling, surveillance, and management of families with MAP.


Heavy ion therapy: status and perspectives.
Starting with the pioneering work at the University of California in Berkeley in 1977, heavy ion radiotherapy has been of increasing interest especially in Japan and Europe in the last decade. There are currently 3 facilities treating patients with carbon ions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation and the construction of a new hospital based facility at the Heidelberg university will be started soon. An outline of the current status of heavy ion radiotherapy is given with emphasis to the technical aspects of the respective facilities. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The clinical trials and routine treatments performed at the German heavy ion facility are summarized. An overview over the upcoming new facilities and their technical possibilities is given. It is discussed what the necessary improvements are to fully exploit the potential of these facilities. Especially the new Heidelberg facility with the possibility of active beam scanning in combination with the first isocentric gantry for ions and offering beams of protons, helium, oxygen and carbon ions has implications on treatment planning, dosimetry and quality assurance. The necessary and ongoing developments in these areas are summarized. The new facilities also offer the possibilities to perform more extensive clinical studies and to explore future indications for radiotherapy with heavy ions. An overview over the indications and treatment schemes is also given.


Cloning and functional expression of a novel geranylgeranyl pyrophosphate synthase gene from Arabidopsis thaliana in Escherichia coli.
A gene encoding a novel geranylgeranyl pyrophosphate (GGPP) synthase from Arabidopsis thaliana has been identified and termed GGPS5. The gene has been sequenced and expressed in Escherichia coli. The deduced amino acid sequence showed 64.5% and 57.5% identify with a putative GGPP synthase from Arabidopsis and Capsicum annuum, respectively. GGPP enzymatic activity was detected in E. coli cells expressing the GGPS5 gene in two different ways. One was the direct measurement of GGPP synthase activity in cell extracts and the other was the yellow color production of cells when the GGPS5 gene was co-expressed with crtB, crtI, crtY and crtZ genes derived from Erwinia uredovora.


The perceptual consequences and neurophysiology of eye blinks.
A hand passing in front of a camera produces a large and obvious disruption of a video. Yet the closure of the eyelid during a blink, which lasts for hundreds of milliseconds and occurs thousands of times per day, typically goes unnoticed. What are the neural mechanisms that mediate our uninterrupted visual experience despite frequent occlusion of the eyes? Here, we review the existing literature on the neurophysiology, perceptual consequences, and behavioral dynamics of blinks. We begin by detailing the kinematics of the eyelid that define a blink. We next discuss the ways in which blinks alter visual function by occluding the pupil, decreasing visual sensitivity, and moving the eyes. Then, to anchor our understanding, we review the similarities between blinks and other actions that lead to reductions in visual sensitivity, such as saccadic eye movements. The similarity between these two actions has led to suggestions that they share a common neural substrate. We consider the extent of overlap in their neural circuits and go on to explain how recent findings regarding saccade suppression cast doubt on the strong version of the shared mechanism hypothesis. We also evaluate alternative explanations of how blink-related processes modulate neural activity to maintain visual stability: a reverberating corticothalamic loop to maintain information in the face of lid closure; and a suppression of visual transients related to lid closure. Next, we survey the many areas throughout the brain that contribute to the execution of, regulation of, or response to blinks. Regardless of the underlying mechanisms, blinks drastically attenuate our visual abilities, yet these perturbations fail to reach awareness. We conclude by outlining opportunities for future work to better understand how the brain maintains visual perception in the face of eye blinks. Future work will likely benefit from incorporating theories of perceptual stability, neurophysiology, and novel behavior paradigms to address issues central to our understanding of natural visual behavior and for the clinical rehabilitation of active vision.


Map positions of SFR genes in relation to other freezing-related genes of Arabidopsis thaliana.
We determined the map positions of seven SFR genes and compared them to the positions of 51 genes suspected of involvement in freezing tolerance in Arabidopsis thaliana. The SFR genes were recognized by the freezing sensitivity of mutants; the others (including 14 whose map positions we have determined) were genes whose expression is induced by low temperature, genes involved in abscisic acid (ABA) biosynthesis and perception, and genes involved in tolerance of oxidative stress. The comparison of map positions indicated a limited set of potential identities, some of which were eliminated by further mapping or by an allelism test.


A note on 'plotless' methods for estimating bacterial cell densities.
' Plotless ' techniques for determining population densities have been developed for, and applied to, higher plant populations. They can often be carried out more rapidly than techniques involving total counts of individuals in plots, or quadrants, but such plotless techniques have not been generally applied to the estimation of densities of bacterial cells. Direct microscopical counting of cell numbers in a field of view, an example of a plot-related method, has been traditionally used for microbial cell counts. In this study 'plot' and ' plotless ' methods on a variety of bacterial samples are compared. Estimates of bacterial cell density were obtained by measuring the distance of cells from a fixed point in a field of view. The values, which were more rapidly obtained, were directly correlated with total cell counts. Although there was some apparent deviation from a perfect 1:1 relationship with total counts, as indicated by a correlation coefficient less than 1.0, there were no significant differences between the replicated counts of bacteria on samples of tissue from the surface of Hypholoma basidiocarps (P less than 0.05). This indicated that the methods of enumeration were comparable. The distance-related estimates could readily be obtained from fields of view with cell densities varying over several orders of magnitude. It was more rapidly applied, particularly at high density, and the method was applicable not only to random cell distributions but also to the non-random distributions encountered when microbial cells aggregated into microcolonies. The method appears to be particularly well-suited for automated, digitized, direct counting procedures, as well as to estimating bacterial numbers on membrane filters and natural substrates.


Direct and simultaneous observation of ultrafast electron and hole dynamics in germanium.
Understanding excited carrier dynamics in semiconductors is crucial for the development of photovoltaics and efficient photonic devices. However, overlapping spectral features in optical pump-probe spectroscopy often render assignments of separate electron and hole carrier dynamics ambiguous. Here, ultrafast electron and hole dynamics in germanium nanocrystalline thin films are directly and simultaneously observed by ultrafast transient absorption spectroscopy in the extreme ultraviolet at the germanium M4,5 edge. We decompose the spectra into contributions of electronic state blocking and photo-induced band shifts at a carrier density of 8 × 1020 cm-3. Separate electron and hole relaxation times are observed as a function of hot carrier energies. A first-order electron and hole decay of ∼1 ps suggests a Shockley-Read-Hall recombination mechanism. The simultaneous observation of electrons and holes with extreme ultraviolet transient absorption spectroscopy paves the way for investigating few- to sub-femtosecond dynamics of both holes and electrons in complex semiconductor materials and across junctions.


Combination of Mandibular Constriction and Intraoral Vertical Ramus Osteotomies for a Transverse Jaw Discrepancy.
The aim of the present study was to evaluate the treatment of patients developing a transverse jaw width discrepancy who exhibited class III malocclusion and/or facial asymmetry by a combination of mandibular constriction (MC) and intraoral vertical ramus osteotomies (IVROs). In a retrospective study, functional results, postoperative complications, and skeletal stability were analyzed for all the patients who had undergone MC and IVRO, with more than 2 years of follow-up. A mandibular midline osteotomy for constriction with lag screw technique and IVROs was used for MC and setback. Sixteen patients were included in the present study. The average degree of MC was 6.34 mm. Both the occlusal relationship and facial appearance in all patients were significantly improved by the surgical orthodontic treatment, with no harmful clinical symptoms. In addition, our original MC using lag screw technique provided the most reliable results in terms of skeletal stability. This study showed that MC using lag screw technique gives a very stable mandibular width constriction, and the combination of MC and IVROs offers a promising treatment alternative for patients with mandibular prognathism developing a transverse jaw width discrepancy.


BLOC-1, a novel complex containing the pallidin and muted proteins involved in the biogenesis of melanosomes and platelet-dense granules.
Recent studies have led to the identification of a group of genes required for normal biogenesis of lysosome-related organelles such as melanosomes and platelet-dense granules. Two of these genes, which are defective in the pallid and muted mutant mouse strains, encode small, coiled-coil-forming proteins that display no homology to each other or to any known protein. We report that these two proteins, pallidin and muted, are components of a novel protein complex. We raised antibodies that allow for detection of pallidin from a wide variety of mammalian cells. Endogenous pallidin was distributed in both soluble and peripheral membrane protein fractions. Size-exclusion chromatography and sedimentation velocity analyses indicated that the bulk of cytosolic pallidin is a component of an asymmetric protein complex with a molecular mass of approximately 200 kDa. We named this complex BLOC-1 (for biogenesis of lysosome-related organelles complex 1). Steady-state pallidin protein levels were reduced in fibroblasts derived from muted and reduced pigmentation mice, suggesting that the genes defective in these two mutant strains could encode components of BLOC-1 that are required for pallidin stability. Co-immunoprecipitation and immunodepletion experiments using an antibody to muted confirmed that this protein is a subunit of BLOC-1. Yeast two-hybrid analyses revealed that pallidin is capable of self-association through a region that contains its two coiled-coil forming domains. Unlike AP-3-deficient pearl fibroblasts, which display defects in intracellular zinc storage, zinc distribution was not noticeably affected in pallid or muted fibroblasts. Interestingly, immunofluorescence and in vitro binding experiments demonstrated that pallidin/BLOC-1 is able to associate with actin filaments. We propose that BLOC-1 mediates the biogenesis of lysosome-related organelles by a mechanism that may involve self-assembly and interaction with the actin cytoskeleton.


Correlating Lipid Membrane Permeabilities of Imidazolium Ionic Liquids with their Cytotoxicities on Yeast, Bacterial, and Mammalian Cells.
Alkyl-imidazolium chloride ionic liquids (ILs) have been broadly studied for biochemical and biomedical technologies. They can permeabilize lipid bilayer membranes and have cytotoxic effects, which makes them targets for drug delivery biomaterials. We assessed the lipid-membrane permeabilities of ILs with increasing alkyl chain lengths from ethyl to octyl groups on large unilamellar vesicles using a trapped-fluorophore fluorescence lifetime-based leakage experiment. Only the most hydrophobic IL, with the octyl chain, permeabilizes vesicles, and the concentration required for permeabilization corresponds to its critical micelle concentration. To correlate the model vesicle studies with biological cells, we quantified the IL permeabilities and cytotoxicities on different cell lines including bacterial, yeast, and ovine blood cells. The IL permeabilities on vesicles strongly correlate with permeabilities and minimum inhibitory concentrations on biological cells. Despite exhibiting a broad range of lipid compositions, the ILs appear to have similar effects on the vesicles and cell membranes.


The value of qualitative methods to public health research, policy and practice.
This article reviews the role and use of qualitative methods in public health research.'Signs of quality' are introduced to help guide potential authors to publish their qualitative research in public health journals. We conclude that high-quality qualitative research offers insights that quantitative research cannot. It is time for all public health journals to recognise the value of qualitative research and increase the amount that they publish.


Five new species of Pseudorhabdosynochus (Monogenea: Diplectanidae) from the gills of Epinephelus costae (Teleostei: Serranidae).
A survey of the gill parasites of Epinephelus costae (Teleostei: Serranidae) was conducted between 2001 and 2005 in the Gulf of Gabès (Tunisia). Five new species of Diplectanidae (Monogenea) were collected, all belonging to Pseudorhabdosynochus Yamaguti, 1958: P. bouaini sp. n., P. dolicocolpos sp. n., P. enitsuji sp. n., P. sinediscus sp. n., and P. sosia sp. n. These five species differ from each other and from all described species of Pseudorhabdosynochus by the morphology and size of their sclerotized vagina. These diplectanids (except P. sinediscus) were also collected from the same host off Dakar in 1981 and 1989. The present paper includes the descriptions and taxonomic considerations of each of these species in addition to an amended diagnosis of Pseudorhabdosynochus. A key to the five new species parasitizing E. costae is provided. These five species are the first diplectanids described from E. costae.


The global epidemic of obesity.
Obesity is at last being recognized as a major public health problem of global significance. More quality national obesity prevalence data are urgently needed but it is clear that rates are already high and increasing in most parts of the world. Current estimates of the global prevalence exceed 250 million. The first formal World Health Organization Consultation on obesity concluded that the global epidemic is an unintended consequence of modernization, economic development, urbanization and other societal changes. These have led to widespread reductions in spontaneous and work-related physical activity and to excessive consumption of energy dense foods. Links between reduced growth in utero and increased risk of ill health in later life may partly explain why populations in many developing countries are especially susceptible to obesity, diabetes and heart disease when exposed to modern sedentary living. The International Obesity TaskForce has launched a global initiative for coherent action to tackle the epidemic.


Inhibition of calcium/calmodulin-dependent protein kinase II normalizes diabetes-induced abnormal vascular reactivity in the rat perfused mesenteric vascular bed.
1. Calcium/calmodulin-dependent protein kinase II (CaMKII) has an important function in mediating insulin release but its role in the development of diabetes-induced cardiovascular complications is not known. 2. We investigated the ability of a chronic administration of KN-93 (5 mg kg(-1) alt diem for 4 weeks), an inhibitor of CaMKII, to modulate the altered vasoreactivity of the perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)-induced diabetes. 3. The vasoconstrictor responses induced by noradrenaline (NE), endothelin-1 (ET-1), and angiotensin II (Ang II), were significantly increased whereas, vasodilator responses to carbachol and histamine were significantly reduced in the perfused mesenteric bed of the STZ-diabetic rats as compared with non-diabetic controls. 4. Inhibition of CaMKII by KN-93 treatment did not affect blood glucose levels but produced a significant normalization of the altered agonist-induced vasoconstrictor and vasodilator responses. KN-93 did not affect agonist-induced responses in control animals. In addition, KN-93 significantly reduced weight loss in diabetic rats. 5. The present data suggest that CaMKII is an essential mediator in the development of diabetic vascular dysfunction and may also play an important role in signalling pathways leading to weight loss during diabetes.


The placebo response in medicine: minimize, maximize or personalize?
Our understanding of the mechanisms mediating or moderating the placebo response to medicines has grown substantially over the past decade and offers the opportunity to capitalize on its benefits in future drug development as well as in clinical practice. In this article, we discuss three strategies that could be used to modulate the placebo response, depending on which stage of the drug development process they are applied. In clinical trials the placebo effect should be minimized to optimize drug-placebo differences, thus ensuring that the efficacy of the investigational drug can be truly evaluated. Once the drug is approved and in clinical use, placebo effects should be maximized by harnessing patients' expectations and learning mechanisms to improve treatment outcomes. Finally, personalizing placebo responses - which involves considering an individual's genetic predisposition, personality, past medical history and treatment experience - could also maximize therapeutic outcomes.


Biliary atresia: current management and outcome.
Between 1986 and 1994, 42 patients with BA were treated at the Kobe Children's Hospital. These patients underwent a wider excision of the hilar fibrous remnant with Roux-Y reconstruction (with or without intussuscepted valve) without stoma. Corticosteroids were used postoperatively when the stool was acholic or unsteadily cholic. The daily dose was reduced from 20 mg/day by half down. The patients were divided into two groups; in Group I (n = 17, before October 1990), a single course of corticosteroid therapy was employed. In Group II (n = 25, from November 1990 on), this regimen was repeated whenever the stool appeared less cholic. The bile flow improved significantly (excellent in 29% and 60%, and poor in 71% and 32% in Groups I and II, respectively.) Corticosteroids were used in 15 Group I patients with good response in 10 and in 21 Group II patients, 15 of whom had multiple courses. Sixteen of the 21 Group II patients had a good response. The incidence of the cholangitis was not significantly different between the 19 patients with valve and the 23 patients without valve. A 5 year survival significantly improved from 70% in Group I to 96% in Group II. In both groups, the survival rate significantly increased, when compared with the survival rate figured out with an assumption of OLT survivors as dead. On the same assumption, the survival rate of Group II is significantly more than that of the Group II. These suggest a positive contribution of liver transplantation and an aggressive corticosteroid therapy on better survival of Group II.


Effects of ankle support on lower-extremity functional performance: a meta-analysis.
Clinicians surmise that the application of external ankle support reduces the ability to perform functional skills and movements, but the outcomes from some of these studies have been inconclusive. To meta-analyze studies regarding the effects of external ankle support on lower-extremity functional performance measures. A total of 93 effects from 17 randomized controlled trials utilizing predominantly crossover designs with recreationally active participants and competitive athletes were subjected to a random-effects meta-analysis. The treatment variable was external ankle support with three levels: adhesive tape, lace-up style, and semirigid style. Differences between mean changes in treatment and control groups were computed as standardized effect sizes for sprint, agility, and vertical jump performance with their 90% confidence intervals (CI). Effect sizes >0.20 were considered substantial. The greatest effect of ankle support on performance was a negative effect of lace-up style brace on sprint speed (effect size -0.22, 90% CI -0.47 to 0.03), equivalent to approximately 1% impairment of speed. The other effects of external ankle support on performance were insubstantial, though most were negative, and their lower confidence limits allowed for realistic chances of impaired performance. Substantial true variation between studies, although poorly defined, was also present for some effects, further increasing the likelihood of performance impairment in some settings. More research is needed to reduce the uncertainty in the effects of external ankle support on performance. In the meantime, it is our opinion that the benefit in preventing injury outweighs the possibility of substantial but small impairment of performance when athletes use external ankle support.


Identification of High-Risk Subgroups of Patients With Oral Cavity Cancer in Need of Postoperative Adjuvant Radiotherapy or Chemo-Radiotherapy.
Patients with oral cavity squamous cell carcinoma (OSCC) undergoing surgery are recommended to receive adjuvant radiation therapy with or without chemotherapy if there are unfavorable prognostic factors. A positive resection margin (PRM) and extra-capsular extension (ECE) of lymph nodes are well-known major prognostic factors. However, there is no agreement on whether oral cavity cancer patients should receive postoperative chemo-radiotherapy (CCRT) if they present with other risk factors or a combination of 2 or more risk factors. In this study, we investigated this issue and provide suggestions for adjuvant treatments.From January 2002 to December 2013, 567 OSCC patients who had undergone radical surgery were retrospectively reviewed. The 5-year loco-regional control (LRC), distant metastasis-free (DMF), disease-free survival (DFS), and overall survival (OS) were analyzed.In univariate analysis, pathological T classification, positive node, tumor depth, ECE, lymphatic or vascular or perineural invasion and histology grade are significant prognostic factors for LRC, DMF, DFS, or OS. By multivariate analysis, pathological T4 (pT4), positive node, positive surgical margin are prognostic factors for LRC. pT4, positive node and lymphatic invasion predicted for higher rate of distant metastasis. pT4, positive node, and poor differentiation tumor were prognostic factors for DFS. pT4, positive nodes, and ECE were prognostic factors for OS. These factors were used to define risk groups. We proposed PRM and ECE as major risk factors and pT4, positive nodes, close margin (≤ 5 mm, > 1 mm), tumor depth ≥ 1 cm, lymphatic invasion, vascular invasion, perineural invasion, and poor differentiation as minor risk factors. By subgroups analysis, 192 patients with at least 2 minor prognostic factors and no other major risk factors, postoperative radiotherapy (RT), or CCRT yielded significantly better 5-year LRC, DFS, and OS compared to surgery only group. For 179 patients with at least 3 minor prognostic factors and/or at least 1 major risk factor, patients receiving postoperative CCRT showed significantly better 5-year LRC, DFS, and OS compared with post-OP RT or surgery alone.Patients with 2 minor risk factors should receive postoperative RT. For patients with PRM, ECE, or >2 minor risk factors, postoperative CCRT is recommended.


Modeling noise-induced resonance in an excitable system: an alternative approach.
Recently, it has been observed [Md. Nurujjaman, Phy. Rev. E 80, 015201(R) (2009)] that in an excitable system, one can maintain noise-induced coherency in the coherence resonance by blocking the destructive effect of the noise on the system at higher noise level. This phenomenon of constant coherence resonance (CCR) cannot be explained by the existing way of simulation of the model equations of an excitable system with added noise. In this paper, we have proposed a general model which explains the noise-induced resonance phenomenon CCR as well as coherence resonance (CR) and stochastic resonance (SR). The simulation has been carried out considering the basic mechanism of noise-induced resonance phenomena: noise only perturbs the system control parameter to excite coherent oscillations, taking proper precautions so that the destructive effect of noise does not affect the system. In this approach, the CR has been obtained from the interference between the system output and noise and the SR has been obtained by adding noise and a subthreshold signal. This also explains the observation of the frequency shift of coherent oscillations in the CCR with noise level.


Phosphorescent Decanuclear Bimetallic Pt6M4 (M = Zn, Fe) Tetrahedral Cages.
Coordination-driven self-assembly delivers discrete, nanoscopic architectures that may preserve or enhance the physicochemical properties of their parent building blocks. Herein, we report the syntheses, characterization, and photophysical properties of two tetrahedral cages, [ZnII4L6](PF6)8 (C1) and [FeII4L6](OTf)8 (C2), where L = PtII(PEt3)2(C≡C-bpy)2 (PEt3 = triethylphosphine; C≡C-bpy = 5-ethynyl-2,2'-bipyridine) and OTf = trifluoromethanesulfonate. C1 and C2 were assembled in isolated yields of 72% and 81% by treating 2 equiv of Zn(NO3)2·6H2O or Fe(OTf)2 with 3 equiv of L, respectively. Both cages were fully characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction (SCXRD). The local D3 symmetry at each polypyridyl metal node raises the possibility of a number of isomeric cages; however, only the homochiral enantiomers (ΔΔΔΔ and ΛΛΛΛ) are formed based on 1H NMR and SCXRD. C1 exhibits phosphorescence centered at 545 nm with a quantum yield of 10% in N2-degassed acetonitrile at 25 °C. The quantum yield of C2 is significantly lower due to a nonradiative relaxation from 5MC (MC = metal-centered) states introduced by the FeII nodes.


Ready for our children? Results from a survey of upstate New York hospitals' utilization of Pediatric Emergency Preparedness Toolkit guidance.
This project evaluated New York (NY) hospitals outside of New York City (upstate) for their awareness and utilization of the NY State Department of Health Pediatric and Obstetric Emergency Preparedness Toolkit (toolkit) and presence of pediatric emergency preparedness planning elements. A survey assessing toolkit awareness and utilization was distributed to all 145 upstate NY hospitals. Quantitative survey data were analyzed using summary statistics, χ(2) analysis, and odds ratios (OR) in aggregate, by hospital size, and by presence of pediatric medicine/surgery, pediatric intensive care unit (PICU), and/or neonatal ICU (NICU) beds (pediatric beds). Of the 145 hospitals, 116 (80%) completed the survey; 86% of these had reviewed the toolkit. Most had staff clinicians with pediatric expertise, but fewer had appointed pediatric clinical (physician or nurse) coordinators. Hospitals with at least one pediatric bed were more than 2.5 times more likely to have an emergency management plan (EMP) for pediatric patients (P = .0223) and nearly 8 times more likely to have appointed a pediatric physician coordinator (P < .0001) than were hospitals without pediatric beds. Appointment of a pediatric clinical coordinator was significantly associated (P < .001) with presence of various pediatric emergency plan elements (OR range: 3.06-15.13), while staff pediatric clinical expertise or toolkit review were not. Appointment of at least one pediatric clinical coordinator and the presence of one or more pediatric beds were significantly associated with having developed key EMP pediatric elements. Further research should examine barriers to pediatric clinical coordinator appointment and explore the awareness that pediatric patients may arrive at nonpediatric hospitals during a disaster with no option for transfer.


Magnetic core test stand for energy loss and permeability measurements at a high constant magnetization rate and test results for nanocrystalline and ferrite materials.
A test stand was developed to measure the energy losses and unsaturated permeability of toroidal magnetic cores, relevant to applications of magnetic switching requiring a constant magnetization rate of the order of 1-10 T/micros. These applications in pulsed power include linear induction accelerators, pulse transformers, and discharge switches. The test stand consists of a coaxial transmission line pulse charged up to 100 kV that is discharged into a magnetic core load. Suitable diagnostics measure the voltage across and the current through a winding on the magnetic core load, from which the energy losses and unsaturated permeability are calculated. The development of the test stand is discussed, and test results for ferrite CN20 and the nanocrystalline material Finemet FT-1HS are compared to demonstrate the unique properties of a nanocrystalline material. The experimental data are compared with published data in a similar parameter space to demonstrate the efficacy of the experimental methods.


Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model.
Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare. Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model. We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells. These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.


[Surgical policy for patients with prolonged esophageal burn strictures].
Concept of early radical surgical treatment of prolonged esophageal burn strictures (PEBS) is presented. From 1980 to 2000 one-stage esophagoplasty was performed in 503 (62.0%) of 811 patients with PEBS. Bouginage was effective in 17.2% patients. Extirpation of the esophagus with posteriormediastinal plastic repair was performed in 119 patients. Mean age of patients was 48 years, mean anamnesis time--11 years. 13 (10.9%) patients had total PEBS. Combined burn of the stomach was revealed in 25 (21.0%), of the pharynx--in 4 (3.4%) patients. Isoperistaltic gastric tube was used in 102 (85.7%) patients, whole stomach--in 1 (0.8%), left half of the large intestine (antiperistaltic)--in 16 (13.4%) patients. Esophagectomy was performed transiatally in 114 (95.8%), from three approaches (+ right-sided thoracotomy)--in 5 (4.2%) patients. Transplant on the neck was connected with esophagus in 106 (89.1%) patients, with the pharynx--in 13 (10.9%). Combined operations were performed in 14 (11.8%) patients. Intraoperative complications were in 6 (5.0%), postoperative--in 39 (33.0%) patients. Insufficiency of cervical anastomosis was seen in 16 (13.4%), paresis of recurrent nerve--in 4 (3.4%) patients. Hospital lethality was 3.4% (4 patients). Good and satisfactory long-term results of esophagoplasty were achieved in 97 (97.0%) patients. PEBS is the indication for transhiatal extirpation of the esophagus with its one-stage plastic repair with gastric tube (or large intestine) during first 6 months after burn.


Effect of DNA loop anchorage regions (LARs) and microinjection timing on expression of beta-galactosidase gene injected into one-cell rabbit embryos.
The conditions favoring expression of a reporter gene microinjected into a male pronucleus of naturally ovulated and fertilized rabbit eggs have been studied. Injection of the reporter gene during S phase of the cell-cycle allows the highest level of expression of the gene. Incorporation of DNA loop anchorage regions (LARs) into constructs upstream and/or downstream of the reporter gene significantly increased the efficiency of expression. In all cases the expression of the microinjected gene started after a period of transcriptional quiescence, i.e., together with the expression of the host genome. Correct targeting of microinjected constructs within the nuclei via interaction of LAR elements with receptor sites on the nucleoskeleton may facilitate expression of injected DNA constructs as well as their integration into host cell DNA.


Development and implementation of an information management and information technology strategy for improving healthcare services: a case study.
PeaceHealth is a multistate, not-for-profit integrated delivery network that owns and operates five acute care hospitals, one critical access hospital, and twenty-five outpatient clinics. PeaceHealth employs approximately two hundred physicians and seventy allied health professionals; it has relationships with one thousand affiliated physicians. In 1990, PeaceHealth developed a set of strategic priorities for delivering seamless care across the continuum, and creating partnerships between caregivers and patient-consumers. A major component of these strategies was development and implementation of the technology, knowledge, organizational, and community infrastructures that would support delivering and using high-quality, timely information when and where it is needed for effective clinical, operational, and financial decision making. Executing this strategy has resulted in implementation of standard enterprisewide information systems, including a computer-based patient record system in inpatient and outpatient settings, tactical and strategic decision support systems, a well-developed intranet and access to the Internet, and a knowledgeable workforce that have enabled PeaceHealth to support and improve its services and business by bringing interactive information directly to patients, caregivers, managers, directors, and executives. This case study discusses the drivers behind the development of this strategy, specific components of the information management and information technology infrastructure, examples of the impact they have had on patients, caregivers, and the organization, and lessons learned.


Abiraterone acetate and prednisone in chemotherapy-naïve prostate cancer patients: rationale, evidence and clinical utility.
Abiraterone acetate 1000 mg/day, combined with prednisone 5 mg PO twice daily, is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate is the oral prodrug of abiraterone, a specific CYP17 inhibitor that blocks androgen biosynthesis within the adrenal glands, testes and tumor microenvironment. In a phase III trial of men with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC, treatment with oral abiraterone acetate plus prednisone led to a statistically significant improvement in the co-primary endpoints of overall survival and radiographic progression-free survival when compared with placebo plus prednisone. In long-term follow-up of phase III trials, the incidence of corticosteroid-associated adverse events was 25.5% in the abiraterone acetate plus prednisone arm compared with 23.3% in the placebo plus prednisone arm. The need for regular patient monitoring and appropriate management of symptoms during long-term use of prednisone must be placed in context with the improvement in survival seen with abiraterone plus prednisone. Within the multidisciplinary environment that is emerging to meet quality and cost imperatives, abiraterone acetate plus prednisone is suitable for use in the chemotherapy-naïve population with minimal symptoms as well as in patients who have been treated with docetaxel and may have symptomatic disease. Ongoing trials are evaluating the role of abiraterone acetate plus prednisone in patients with nonmetastatic CRPC and metastatic hormone-sensitive prostate cancer, while further trials in the mCRPC setting are evaluating its use in combination regimens.


C-Glucosyl Xanthone derivative Mangiferin downregulates the JNK3 mediated caspase activation in Almal induced neurotoxicity in differentiated SHSY-5Y neuroblastoma cells.
C-Glucosyl Xanthone derivatives were assessed to inhibit the JNK3 mediated Caspase pathway in Almal (Aluminum Maltolate) induced neurotoxicity in SHSY-5Y cells. Mangiferin was selected among 200 C-Glucosyl Xanthones based on molecular interaction, docking score (-10.22 kcal/mol), binding free energy (-71.12 kcal/mol), ADME/tox properties and by molecular dynamic studies. Further, it was noticed that glycone moiety of Mangiferin forms H-bond with ASN 194, SER 193, GLY 76, and OH group in the first position of the aglycone moiety shows interaction at Met 149 which is exceptionally crucial for JNK3 inhibitory activity. Mangiferin (0.5, 1, 10, 20 and 30 µM) and standard SP600125 (20 µM) treatment increased the cell survival rate against Almal 200 µM, with EC50 of Mangiferin (8 µM) and standard SP600125 (4.9 µM) respectively. Mangiferin significantly impedes kinase activation, indicating suppression of JNK3 signaling with IC50 (98.26 nM). Mangiferin (10 and 15 µM) dose-dependently inhibits the caspase 3, 8, and 9 enzyme activation in comparison to Almal group. Mangiferin demonstrated neuroprotection in SHSY-5Y cells against apoptosis induced by Almal by adapting the architecture of the neurons and increasing their density. Among all Xanthone derivatives, Mangiferin could improve neuronal toxicity by inhibiting JNK3 and down-regulating the Caspase activation.


Growth hormone related to insulin and sugar in nocturnal blood plasma of lactating cows.
Nocturnal blood plasma samples from about 190 indoor-fed cows at varying stages of the lactation cycle showed wide variations in the concentrations of sugar (43-88 mg/100 ml) and acetoacetate (0.12-8.7 mg/100 ml). Plasma immunoreactive insulin decreased and acetoacetate increased with decreasing sugar. Plasma growth hormone (GH) was significantly correlated to insulin (r=-0.24, P less than 0.001) and to sugar (r=-0.15, P less than 0.05), but not to acetoacetate (r=+0.13). Since the plasma level of GH in bovines is known to vary widely from hour to hour, individual cows are poorly represented by single determinations of the hormone. However, in accordance with the results from the correlation tests, different GH averages, about 11 and 9 ng/ml, were found for groups of animals with plasma sugar respectively below and above 70 mg/100 ml. By subgrouping according to insulin levels within sugar ranges, categories could be singled out with GH averages as different as 12.7 ng/ml (low sugar-low insulin) and 8.3 ng/ml (high sugar-high insulin). The findings are consistent with the view that GH is involved in the regulation of energy metabolism in bovines. But no support has been provided for the hypothesis of GH hypersecretion as a cause of ketosis in cows.