Osteoblastic and fibroblastic multicentric osteosarcoma.
Bone sarcomas are uncommon tumours, of which osteosarcoma is the least rare, as well as the third most common malignant tumour in childhood, appearing usually between the 10 and 20 years of age. The case the authors present in this work is of a patient suffering from a long-standing condition encompassing skin and soft tissue lesions. After multiple medical treatments, the patient was diagnosed with squamous osteosarcoma, which required aggressive surgical management and chemotherapy.


Novel selection marker for mammalian cell transfection.
The availability of selectable markers suitable for use in mammalian cells has permitted the analysis of the influence of the stable overexpression of single or multiple genes on specific cell properties. This powerful technique has led directly to many fundamental advances in molecular biology and increased our overall understanding of cell growth and regulatory events. Although a variety of selectable markers are currently available, some cell lines continue to be naturally resistant to certain markers, making direct selection difficult or not feasible. Thus, the characterization of additional cell selectable markers continues to be of interest. We have developed a novel selectable marker based on mitomycin C resistance that is suitable for stable transfection of mammalian cells. This system is based on the ability of the mcrA gene, isolatedfrom Streptomyces lavendulae, to confer mitomycin C resistance to both bacterial and mammalian cells by expression of the MCRA protein. Here we demonstrate that mcrA can be used as a selectable gene marker in Chinese hamster ovary cells when cells transfected with the mcrA gene are either pulsed or cultured continuously with mitomycin C This unique selection system may be of use for transfection of cells that are resistant to currently available selectable markers.


Copper and neurological function.
The role of copper in maintaining normal neurological function has been examined in animals copper-deficient by dietary means, and in the genetic disorders of copper homeostasis -- Menkes' kinky-hair disease in humans and the mottled (Mo) mutants in the mouse. With the exception of the disorder in Mo mice, reduced myelination is a constant feature of these copper diseases but there is otherwise a lack of conformity in the structural defects produced in different species. Dietary copper-deficient animals show a reduction in noradrenaline and dopamine concentrations, together with a depressed tyrosine 3-monooxygenase activity (EC 220.127.116.11). Noradrenaline concentrations are also reduced in brain tissue of Mo mice and this reduction is associated with a decrease in the vivo activity of the copper metalloenzyme, dopamine beta-monooxygenase (EC 126.96.36.199). Many tissues contain potent inhibitors of dopamine beta-monooxygenase activity, and assays of this enzyme have utilized cupric ions to inactivate these inhibitors. The elevated in vitro activities of dopamine beta-monooxygenase obtained for both Mo brain and adrenal tissue may therefore reflect either a reduced inactivation of these endogenous inhibitors in the intact animal or the activation in vitro of apoenzyme. Concentrations of dopamine and tyrosine 3-monooxygenase are unchanged in Mo mice. The reduction in dopamine and tyrosine 3-monooxygenase activity in dietary copper-deficient animals may therefore reflect neuronal loss rather than reduced catalytic activity of the catecholamine biosynthetic pathway. The possible effects of depressed activities of cytochrome c oxidase (EC 22.214.171.124) and superoxide dismutase (EC 184.108.40.206) in the development of neurological dysfunction are also discussed, and attention is drawn to the possible significance of the elevated uptake of neutral amino acids, especially tyrosine and tryptophan, by Mo brain tissue.


Release of axillary scar contracture with a latissimus dorsi flap.
A case is presented of a patient who underwent an elective axillary augmentation that was complicated by hematoma, capsular contracture, and a staphylococcal wound infection. Attempts to correct the deformity with multiple capsulotomies and axillary contracture releases were unsuccessful. Following these procedures, a thick axillary scar contracture formed that was adherent to the breast capsule and severely limited abduction of the arm. The patient underwent release of the axillary scar contracture with a latissimus dorsi muscle flap. The superiorly based lateral portion of the muscle was transposed to fill the dead space between the axillary scar and adherent breast capsule. A Z-plasty was also used to lengthen the cutaneous scar. Abduction of the arm improved to 130 degrees postoperatively. Lengthening of the skin contracture could be provided by a Z-plasty, but separation of the deeper scar matrix required normal soft-tissue interposition. The lateral portion of the latissimus dorsi muscle was chosen to fill this dead space.


Epigenetic age is associated with baseline and 3-year change in frailty in the Canadian Longitudinal Study on Aging.
The trajectory of frailty in older adults is important to public health; therefore, markers that may help predict this and other important outcomes could be beneficial. Epigenetic clocks have been developed and are associated with various health-related outcomes and sociodemographic factors, but associations with frailty are poorly described. Further, it is uncertain whether newer generations of epigenetic clocks, trained on variables other than chronological age, would be more strongly associated with frailty than earlier developed clocks. Using data from the Canadian Longitudinal Study on Aging (CLSA), we tested the hypothesis that clocks trained on phenotypic markers of health or mortality (i.e., Dunedin PoAm, GrimAge, PhenoAge and Zhang in Nat Commun 8:14617, 2017) would best predict changes in a 76-item frailty index (FI) over a 3-year interval, as compared to clocks trained on chronological age (i.e., Hannum in Mol Cell 49:359-367, 2013, Horvath in Genome Biol 14:R115, 2013, Lin in Aging 8:394-401, 2016, and Yang Genome Biol 17:205, 2016). We show that in 1446 participants, phenotype/mortality-trained clocks outperformed age-trained clocks with regard to the association with baseline frailty (mean = 0.141, SD = 0.075), the greatest of which is GrimAge, where a 1-SD increase in ΔGrimAge (i.e., the difference from chronological age) was associated with a 0.020 increase in frailty (95% CI 0.016, 0.024), or ~ 27% relative to the SD in frailty. Only GrimAge and Hannum (Mol Cell 49:359-367, 2013) were significantly associated with change in frailty over time, where a 1-SD increase in ΔGrimAge and ΔHannum 2013 was associated with a 0.0030 (95% CI 0.0007, 0.0050) and 0.0028 (95% CI 0.0007, 0.0050) increase over 3 years, respectively, or ~ 7% relative to the SD in frailty change. Both prevalence and change in frailty are associated with increased epigenetic age. However, not all clocks are equally sensitive to these outcomes and depend on their underlying relationship with chronological age, healthspan and lifespan. Certain clocks were significantly associated with relatively short-term changes in frailty, thereby supporting their utility in initiatives and interventions to promote healthy aging.


Comparison of demography, diet, lifestyle, and serum lipid levels between the Guangxi Bai Ku Yao and Han populations.
Bai Ku Yao is an isolated subgroup of the Yao minority in China. Little is known about dyslipidemia in this population. The aim of this study was to compare the effects of demography, diet, and lifestyle on serum lipid levels between the Bai Ku Yao and Han populations. A total of 1,170 subjects of Bai Ku Yao and 1,173 subjects of Han Chinese aged 15-89 years were surveyed by a stratified randomized cluster sampling. The levels of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A-I (apoA-I), and apoB were significantly lower in Bai Ku Yao than in Han. Physical activity level and total dietary fiber intake were higher, whereas body mass index (BMI), waist circumference, total energy intake, and total fat intake were lower in Bai Ku Yao than in Han. Hyperlipidemia was positively correlated with BMI, waist circumference, and total energy and total fat intakes and negatively associated with physical activity level and total dietary fiber intake in both populations, but it was positively associated with age and alcohol consumption only in Han. The differences in the lipid profiles between the two ethnic groups were associated with different dietary habits, lifestyle choices, and levels of physical activities.


Improved detection of HLA-Cw5 and Cw7 by two colour fluorescence technique.
Reactivity of two Cw5 and three Cw7 antisera was compared in the standard NIH and the Two Colour Fluorescence (TCF) techniques. Contrary to the NIH, the TCF method yielded strong positive reactions which enabled clear assignment of the Cw5 and Cw7 specificities. The TCF technique combines three factors that increase the sensitivity of serum reactions: 1. typing on B lymphocytes, 2. prolonged incubation and 3. staining of the lysed cells with ethidium bromide.


[Expression of vascular endothelial growth factor A and C in human breast cancer and their significance].
Vascular endothelial growth factor (VEGF) family is related to angiogenesis. VEGF-A and VEGF-C are closely related to tumorigenesis and lymphatic metastasis. This study was to detect the expression of VEGF-A and VEGF-C in breast cancer, and explore their correlation to cell proliferation, microvessel density (MVD), and lymphatic metastasis of breast cancer. The expression of VEGF-A, VEGF-C, proliferating cell nuclear antigen (PCNA), and CD34 in 98 samples of breast cancer were detected by SP immunohistochemistry. The positive rate of VEGF-A was 85.7%; that of VEGF-C was 90.8%. The positive rates of VEGF-A and VEGF-C were significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis (P<0.05). The positive rate of PCNA was 98.0%; its expression level was increased with the expression levels of VEGF-A and VEGF-C (r=0.432, P=0.000; r=0.294, P=0.001). MVD was significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis(64.26+/-26.40 vs. 50.29+/-29.35, P<0.05). MVD was positively correlated to the expression of VEGF-A (r=0.327, P<0.001), but had no correlation to VEGF-C (r=0.123, P>0.05). VEGF-A mainly mediates angiogenesis, cell proliferation, and metastasis of human breast cancer. VEGF-C promotes cell proliferation of human breast cancer; it is correlated to lymph node metastasis, but has no correlation to MVD.


Occupation and parkinsonism in three movement disorders clinics.
Few occupational risk factors for Parkinson disease (PD) have been identified. Healthcare, teaching, and farming have been associated with increased risk, while welding has been proposed to accelerate age at PD onset. The aim of the present study was to investigate occupational associations with PD or parkinsonism drawing from three different movement disorders clinics. Medical records of 2,249 consecutive patients with PD or parkinsonism from specialty clinics in Sunnyvale, CA, New York, NY, and Atlanta, GA, were reviewed for primary lifetime occupation. Job frequencies were compared with Department of Labor regional statistics. PD diagnosis age and risk of diagnosis < or =50 were determined for each job. Physicians/dentists, farmers, and teachers were significantly more common than expected among PD patients, as were lawyers, scientists, and religion-related jobs. Computer programmers had a younger age at PD diagnosis, and risk of diagnosis < or =50 was greater in computer programmers and technicians. Consistent with prior studies, healthcare, teaching, and farming were common occupations in Parkinson disease (PD) patients, but welders were not over-represented. Even though several occupations were associated with younger age at PD diagnosis, these results may reflect biases inherent in specialty clinic surveys, including over-representation of younger, employed, and insured patients. Carefully designed analytic studies utilizing appropriate control populations will be required to test hypotheses regarding occupation and PD risk.


Effects of lectins and tunicamycin on IL-1 binding to YT cells.
Specific binding of iodinated-interleukin-1 alpha or beta to YT cells could be inhibited by the lectins wheat germ agglutinin (WGA) and concanavalin A (Con A). WGA and Con A inhibition of IL-1 binding was abrogated by previous exposure of these plant proteins to the lectin-specific sugars N-acetylglucosamine (GlcNAc) and methyl glucoside (MG), respectively. Tunicamycin, an inhibitor of glycosylation, decreased interleukin-1 (IL-1) binding to YT cells, but also reduced total protein synthesis. These observations suggest that carbohydrate moieties on or near the interleukin-1 receptor may be important for optimal receptor binding of IL-1 to intact YT cells.


Efficacy of auricular plaster therapy for sleep disorders in preschool children with autism spectrum disorders: Study protocol for a randomized controlled trial.
Children with autism spectrum disorders (ASDs) suffer from sleep disorders to a considerable degree; however, there is no safe and effective treatment available in clinical practice. The objective of the trial is to assess the clinical effectiveness of auricular plaster therapy (APT) in treating sleep disorders in children with ASD. This is a single-center, patient-assessor blind, randomized controlled trial. A total of 44 preschool children with sleep disorders with ASD will be included in this study. Eligible participants will be randomly assigned to either the auricular plaster group or the sham auricular plaster group in a 1:1 ratio. Participants in the different groups will receive APT or sham APT, respectively, for a total of 30 sessions over 30 days. The primary outcome includes the Children's Sleep Habits Questionnaire (CSHQ), while secondary outcomes include the Autism Behavior Checklist (ABC) and polysomnography (PSG) for total sleep time, sleep latency, awakening duration, and sleep structures. The CSHQ and ABC will be assessed at baseline, 10, 20, 30, 60, 90, and 120 days after randomization, whereas PSG will be assessed at baseline and 30 days after randomization. The follow-up period will be scheduled to be 60, 90, and 120 days after randomization. The results of this study may provide evidence of the efficacy of APT, as well as offer new alternatives for the treatment of sleep disorders in children with ASD. CHiCTR.org.cn (ChiCTR2100048257). Registered on July 5, 2021.


(-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.
(-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination. Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor. Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.


Body Composition of Infants With Congenital Gastroschisis.
Infants born with congenital gastroschisis are at risk for intrauterine growth restriction, small for gestational size at birth, and growth failure during the newborn period despite advanced care. Body composition provides a more complete picture of proportional growth than weight and length alone. Fat-free mass (FFM) represents organ growth, and in preterm infants without gastroschisis, improved FFM deposition is associated with improved neurodevelopmental outcomes. There is limited literature regarding the body composition of infants with gastroschisis. This case series describes the body composition of 10 infants with gastroschisis.


Effects of brown seaweed polyphenols, α-tocopherol, and ascorbic acid on protein oxidation and textural properties of fish mince (Pagrosomus major) during frozen storage.
Frozen storage of minced fish is currently one of the most important techniques to maintain its functional properties. However, some deterioration does occur during frozen storage and cause quality loss. The effects of brown seaweed polyphenols, α-tocopherol, and ascorbic acid on lipid and protein oxidation and textural properties of red sea bream (Pagrosomus major) during 90 days of frozen storage at -18 °C were investigated. All added antioxidants at 1 g kg-1 resulted in significantly lower thiobarbituric acid-reactive substances (TBARS) compared to the control during the 45 days of frozen storage. The antioxidants were also effective in retarding protein oxidation concerning to total sulfhydryl content and protein carbonyl content. Brown seaweed polyphenols and α-tocopherol significantly retarded the inactivation of Ca2+ -ATPase activity during the first 45 days, whereas ascorbic acid had no such effect. The antioxidant activity showed either an invariable or decrease trend after 45 days storage. Adding antioxidants had a significant effect on the breaking force of the gels during the frozen storage period. These results indicate that brown seaweed polyphenols and α-tocopherol can be used to prevent oxidative reactions and thus maintain the structure of the gel formed by fish mince during frozen storage. © 2016 Society of Chemical Industry.


Importance of N- and C-terminal residues of substance P 1-7 for alleviating allodynia in mice after peripheral administration.
The heptapeptide SP1-7 (1, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic processing of the neuropeptide substance P (SP, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2). The heptapeptide 1 frequently exhibits opposite effects to those induced by SP, such as exerting antinociception, or attenuating thermal hyperalgesia and mechanical allodynia. The heptapeptide SP1-7 amide (2, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) is often more efficacious than 1 in experimental pain models. We have now assessed the anti-allodynic outcome after systemic administration of 2 and a series of Ala-substituted and truncated analogues of 2, in the spared nerve injury (SNI) mice model and the results obtained were correlated with in vitro plasma stability and permeability measurements. It is herein demonstrated that an intact Arg1 in SP1-7 amide analogues is fundamental for retaining a potent in vivo effect, while Lys3 of 2 is less important. A displacement with Ala1 or truncation rendered the peptide analogues either inactive or with a significantly attenuated in vivo activity. Thus, the pentapeptide SP3-7 amide (7, t1/2=11.1 min) proven to be the major metabolite of 2, demonstrated an in vivo effect itself although considerably less significant than 2 in the SNI model. Intraperitoneal administration of 2 in a low dose furnished the most powerful anti-allodynic effect in the SNI model of all the analogous evaluated, despite a fast proteolysis of 2 in plasma (t1/2=6.4 min). It is concluded that not only the C-terminal residue, that we previously demonstrated, but also the N-terminal with its basic side chain, are important for achieving effective pain relief. This information is of value for the further design process aimed at identifying more drug-like SP1-7 amide related peptidomimetics with pronounced anti-allodynic effects.


[Carcino-embryonic antigen and beta 2 microglobulin in malignant bone diseases. 61 cases (author's transl)].
Radioimmunological assays of carcino-embryonic antigen (CEA) and beta 2 microglobulin were carried out in 61 cases of malignant bone disease, including myeloma and metastases from carcinomas of the breast and prostate. CEA assays seemed to be of greater interest in mammary cancer metastases and beta 2 microglobulin assays in prostatic cancer metastases and myeloma. The correlation which appeared between CEA levels of the outcome of breast cancer metastases was of assistance in adjusting treatment. Combining CEA and beta 2 microglobulin assays would enhance their usefulness in current practice.


FDG-PET/CT in Skeletal Muscle: Pitfalls and Pathologies.
FDG-PET/CT is an integral part of modern-day practice of medicine. By detecting increased cellular metabolism, FDG-PET/CT can help us detect infection, inflammatory disorders, or tumors, and also help us in prognostication of patients. However, one of the most important challenges is to correctly differentiate the abnormal uptake that is potentially pathologic from the physiological uptake. So while interpreting a PET/CT, one must be aware of normal biodistribution and different physiological variants of FDG uptake. Skeletal muscles constitute a large part of our body mass and one of the major users of glucose. Naturally, they are often the site of increased FDG uptake in a PET study. We as a nuclear medicine physician must be aware of all the pitfalls of increased skeletal muscle uptake to differentiate between physiological and pathologic causes. In this review, we have discussed the different causes and patterns of physiological FDG uptake in skeletal muscles. This knowledge of normal physiological variants of FDG uptake in the skeletal muscles is essential for differentiating pathologic uptake from the physiological ones. Also, we reviewed the role of FDG-PET/CT in various benign and malignant diseases involving skeletal muscle.


Creating optimal code for GPU-accelerated CT reconstruction using ant colony optimization.
CT reconstruction algorithms implemented on the GPU are highly sensitive to their implementation details and the hardware they run on. Fine-tuning an implementation for optimal performance can be a time consuming task and require many updates when the hardware changes. There are some techniques that do automatic fine-tuning of GPU code. These techniques, however, are relatively narrow in their fine-tuning and are often based on heuristics which can be inaccurate. The goal of this paper is to present a framework that will automate the process of code optimization with maximum flexibility and produce a final result that is efficient and readable to the user. The authors propose a method that is able to tune high level implementation details by using the ant colony optimization algorithm to find the optimal implementation in a relatively short amount of time. Our framework does this by taking as input, a file that describes a graph, such that a path through this graph represents a potential implementation. They then use the ant colony optimization algorithm to find the optimal path through this graph based on the execution time and the quality of the image. Two experimental studies are carried out. Using the presented framework, they optimize the performance of a GPU accelerated FDK backprojection implementation and a GPU accelerated separable footprint backprojection implementation. The authors demonstrate that the resulting optimal implementation can be different depending on the hardware specifications. They then compare the results of the framework produced with the results produced by manual optimization. The framework they present is a useful tool for increasing programmer productivity and reducing the overhead of leveraging hardware specific resources. By performing an intelligent search, our framework produces a more efficient image reconstruction implementation in a shorter amount of time.


Eukaryotic expression: developments for structural proteomics.
The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for co-expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.


Localization of liposomes containing a DNA repair enzyme in murine skin.
T4N5 liposomes, which contain the DNA repair enzyme T4 endonuclease V, were applied to mouse skin in vivo and added to cultured murine keratinocytes in vitro. The fate of the liposome membrane was followed using a fluorescent, lipophilic dye, and the fate of the enzyme was traced by immunogold labeling, followed by brightfield, fluorescence, or transmission electron microscopy. In vivo, T4N5 liposomes penetrated the stratum corneum, localized in epidermis and appendages of the skin, and were found inside basal keratinocytes. The enzyme was found inside keratinocytes treated in vitro and in the epidermis, hair follicles, and sebaceous glands of topically treated skin. Ultrastructural studies demonstrated the presence of liposomes in the cytoplasm of cells in the epidermis often concentrated in a perinuclear location. The enzyme was present in both nucleus and cytoplasm of keratinocytes and Langerhans cells. Liposomes were found in cells of the lymph nodes draining the site of contact sensitization, in association with topically applied antigen. The results demonstrate that liposomes can deliver encapsulated proteins into cells of the skin in vivo and provide insight into how liposome-enhanced DNA repair reduces UV-induced skin cancer and systemic immunosuppression in mice.


Stimulation of hepatic microsomal beta-glucuronidase by calcium.
Hydrolysis of 3-methylumbelliferyl glucuronide by liver microsomal beta-glucuronidase is enhanced about 2-fold by micromolar concentrations of Ca2+; half-maximal stimulation occurs with 0.35 microM Ca2+. Dissociation of the enzyme from microsomal membranes by various treatments increases basal beta-glucuronidase activity and markedly decreases the sensitivity of the enzyme to Ca2+. Under similar conditions, the soluble lysosomal form of the enzyme is insensitive to Ca2+. Ca2+ stimulation was unaltered by addition of calmodulin inhibitors or exogenous calmodulin. Thus, interaction of cytosolic Ca2+ with membrane bound beta-glucuronidase may modulate glucuronidation in intact hepatocytes via a novel, calmodulin-independent mechanism.


A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.
A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs.


A study of prevalence of Taenia infestation and associated risk factors among the school children of Dharan.
Taenia prevalence has remained high among certain ethnic groups and occupational diseases in Nepal. Taenia saginata and Taenia solium species are worldwide in distribution. Infection is found most often in rural areas of developing countries with poor hygiene and living in close contact with pigs and eating undercooked pork meats. This allows the tapeworm infection to be completed and its cycle to continue. To measure the prevalence of taenia infestation and to identify risk factors associated with taenia infestation among the school children of Dharan. A cross sectional study was conducted among 935 Government and private school going children of Grade VI, VII, and VIII of Dharan during 2007 to 2008. Stratified random sampling method was applied to choose the schools and the study subjects. The prevalence was calculated, Chi-square test was used to measure the association of risk factors and taenia infestation. Taenia species was found to be high (5.5%) among the school children of Dharan. Infection rate of taenia among the male children (6.0%) was slightly higher than female (4.8%). There were no cases of taenia infestation found among children washing hands with soap. Regarding meat consumption in the non-vegetarian group, taenia infestation was found higher (6.5%) among pork eating than nonpork eating (4.7%). No significant relationship was traced among the factors in the causation of taenia infestation although slight indications present. Taenia species was found very high among the school children of Dharan. No such association was found with the risk factors.


A heat-sensitive cellular function located in the nucleolus.
Striking nucleolar lesions occur in cultured cells after exposure to supranormal temperatures. These lesions appear at 42 degrees C and consist of a loss of the granular ribonucleoprotein (RNP) component and intranucleolar chromatin, and a disappearance of the nucleolar reticulum. The material remaining in the morphologically homogeneous nucleolus is a large amount of closely packed fibrillar RNP. The lesions remain identical as temperature increases to 45 degrees C. These alterations are reversible when the cells are returned to 37 degrees C and are associated with the reappearance of an exaggerated amount of intranucleolar chromatin and granular RNP. High-resolution radioautography indicates that after thermic shock nucleolar RNA synthesis is inhibited whereas extranucleolar sites are preserved: it also suggests that the granular RNP is reconverted to fibrillar RNP probably by simple unraveling. The results prove the existence of heat-sensitive cellular functions in the nucleolus which deal with the DNA-dependent RNA synthesis. The precise site of action is assumed to involve hydrogen bonds, resulting in configurational changes in nucleolar RNP and affecting the stability of the DNA molecule. The subsequent events in nucleolar RNA synthesis are discussed in light of the morphologic and biochemical effects of actinomycin D on the nucleolus.


The p53-Bak apoptotic signaling axis plays an essential role in regulating differentiation of the ocular lens.
The tumor suppressor p53 is a master regulator of apoptosis and also plays a key role in cell cycle checking. In our previous studies, we demonstrated that p53 directly regulates Bak in mouse JB6 cells (Qin et al. 2008. Cancer Research. 68(11):4150) and that p53-Bak signaling axis plays an important role in mediating EGCG-induced apoptosis. Here, we demonstrate that the same p53-Bak apoptotic signaling axis executes an essential role in regulating lens cell differentiation. First, during mouse lens development, p53 is expressed and differentially phosphorylated at different residues. Associated with p53 expression, Bak is also significantly expressed during mouse lens development. Second, human p53 directly regulates Bak promoter and Bak expression in p53 knockout mice (p53-/-) was significantly downregulated. Third, during in vitro bFGF-induced lens cell differentiation, knockdown of p53 or Bak leads to significant inhibition of lens cell differentiation. Fourth, besides the major distribution of Bak in cytoplasm, it is also localized in the nucleus in normal lens or bFGF-induced differentiating lens cells. Finally, p53 and Bak are co-localized in both cytoplasm and nucleus, and their interaction regulates the stability of p53. Together, these results demonstrate for the first time that the p53-Bak apoptotic signaling axis plays an essential role in regulating lens differentiation.


Depressed patients who suicide at their first attempt have had few admissions.
A prior suicide attempt is generally considered to be an indicator of increased future suicide risk. However, approximately 50% of psychiatric patients who commit suicide have made no previous suicide attempt. Thus, an effort was made to detect other predictors of future suicide risk in this group. The records of 100 psychiatric patient suicides were examined. Patients who completed suicide at their first attempt (n = 57) were compared with patients who suicided after a previous attempt (n = 43). There were no significant differences between the two groups on any of the sociodemographic or clinical variables examined. However, patients with a primary psychiatric diagnosis of an effective disorder who committed suicide at their first attempt had had significantly less admissions than depressed patients who committed suicide after a previous attempt. The clinical implication is that the absence of many prior admissions in a depressed patient is not an indicator of low suicide risk.


Transcription factors AS1 and AS2 interact with LHP1 to repress KNOX genes in Arabidopsis.
Polycomb group proteins are important repressors of numerous genes in higher eukaryotes. However, the mechanism by which Polycomb group proteins are recruited to specific genes is poorly understood. In Arabidopsis, LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2, was originally proposed as a subunit of polycomb repressive complex 1 (PRC1) that could bind the tri-methylated lysine 27 of histone H3 (H3K27me3) established by the PRC2. In this work, we show that LHP1 mainly functions with PRC2 to establish H3K27me3, but not with PRC1 to catalyze monoubiquitination at lysine 119 of histone H2A. Our results show that complexes of the transcription factors ASYMMETRIC LEAVES 1 (AS1) and AS2 could help to establish the H3K27me3 modification at the chromatin regions of Class-I KNOTTED1-like homeobox (KNOX) genes BREVIPEDICELLUS and KNAT2 via direct interactions with LHP1. Additionally, our transcriptome analysis indicated that there are probably more common target genes of AS1 and LHP1 besides Class-I KNOX genes during leaf development in Arabidopsis.


Strontium-85 profile counting in fractures of the tibial shaft.
A total of 203 profile countings were performed on 68 fractures of the tibial shaft, which included 25 normally healing cases, 37 cases of delayed union, and six cases of non-union. The measurements were performed on the 1st and the 7th day after the injection of strontium. In 27 cases the fracture received 2-3 strontium injections with associated profile counting at different stages of the healing process. The cases of normally healing fractures and delayed union showed differences in the average strontium uptake. However, these differences were not distinct enough to enable classification of individual fractures into groups. In cases requiring bone grafting, the transplant was found to accelerate metabolism and increase the accretion of strontium at the site of the fracture. The investigation shows that the real value of strontium profile counting lies in its ability to give information about the osteogenetic activity of the bone, which is a necessary prerequisite for the healing of the fracture.


A simplified broadband coupling approach applied to chemically robust sol-gel, planar integrated optical waveguides.
A new generation waveguide spectrometer with broadband coupling capabilities has been developed. As opposed to previous devices, this attenuated total reflection (ATR) spectrometer is much simpler in design, is more chemically robust, and transmits light down to at least 400 nm. The attenuated total reflection element consists of a single-mode, planar integrated optical waveguide fabricated by dip-coating a approximately 300 nm thick, sol-gel composite layer on a glass substrate. A commercially available prism is used as the incoupler with an integral holographic diffraction grating acting as the dispersive outcoupling element. The transmission of narrow band-pass filters was used to compare the response of the waveguide spectrometer to that of a conventional transmission instrument. Spectral resolution was assessed by measuring the fwhm of various laser lines, which were found to range from 0.5 to 1.3 nm. The measured limits of detection for the waveguide spectrometer from 400 to 600 nm are 8.0 and 10.1 milliabsorbance units for TE and TM polarizations, respectively. Finally, to demonstrate the application of this technology to a molecular film confined to a solid-liquid interface, visible ATR spectra of an adsorbed submonolayer of horse heart cytochrome c were acquired. A procedure to correct the waveguide spectra for the wavelength dependence in ATR path length is described.


All graphene-based thin film transistors on flexible plastic substrates.
High-performance, flexible all graphene-based thin film transistor (TFT) was fabricated on plastic substrates using a graphene active layer, graphene oxide (GO) dielectrics, and graphene electrodes. The GO dielectrics exhibit a dielectric constant (3.1 at 77 K), low leakage current (17 mA/cm(2)), breakdown bias (1.5 × 10(6) V/cm), and good mechanical flexibility. Graphene-based TFTs showed a hole and electron mobility of 300 and 250 cm(2)/(V·s), respectively, at a drain bias of -0.1 V. Moreover, graphene TFTs on the plastic substrates exhibited remarkably good mechanical flexibility and optical transmittance. This method explores a significant step for the application of graphene toward flexible and stretchable electronics.


Leveling the curve of Spee with continuous archwire appliances in different vertical skeletal patterns: A retrospective study.
The aim of this study was to determine the effects of the leveling of the curve of Spee in subjects treated with preadjusted appliances in different skeletal vertical patterns. The study sample consisted of 90 white patients (39 male, 51 female; age, 19 years 4 months ± 1 year 9 months), with a curve of Spee of 2 mm or greater before treatment. They were categorized into 3 groups: low-angle group (30 subjects; 12 male, 18 female; age, 19 years 1 month ± 1 year 4 months), normal-angle group (30 subjects; 14 male, 16 female; age, 19 years 6 months ± 2 years 1 month), and high-angle group (30 subjects; 13 male, 17 female; age, 19 years 7 months ± 1 year 5 months) by their vertical facial types. Cephalometric parameters were used to evaluate the different dental movements after treatment. The curve of Spee was measured on digital dental casts. Analysis of variance was used to determine any differences between the changes in the groups with time. For the skeletal variables, no significant modifications were found in the 3 groups. For the dentoalveolar variables, the low-angle group showed significant buccal movements and intrusion of the mandibular incisors. The high-angle group had greater extrusion of the posterior teeth associated with uprighting of the first and second molars. In low-angle subjects, leveling of the curve of Spee occurs through buccal movement and intrusion of the mandibular incisors; in high-angle subjects, it occurs through extrusion and uprighting of the posterior teeth.


Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is increasingly used in research and clinical settings to enhance the effects of cognitive training. In our present review, we will first summarize studies using tDCS alone and in combination with cognitive training in older adults and patients with Alzheimer's dementia (AD). We will also review one study (Meinzer et al., 2014c) that showed an improvement in cognitive performance during anodal tDCS over the left inferior frontal cortex in patients with mild cognitive impairment (MCI) which is regarded as a prodromal stage of AD. Although promising short-term results have been reported, evidence from randomized controlled trials (RCTs) with sufficient sample sizes is scarce. In addition, stimulation protocols (in terms of intensity, duration, and repetition of stimulation) that lead to sustained improvements in outcome measures relevant for daily life still remain to be established. Following, we will discuss modulating factors such as technical parameters as well as the question whether there are specific cognitive functions (e.g., learning, memory consolidation, executive control) which are more amenable to tDCS enhancement than others. Finally, we will highlight future directions and limitations in this field and emphasize the need to conduct RCTs to establish efficacy of interventions for activities of daily life for a given patient population.


Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation.
Jeavons syndrome is a common, often misdiagnosed or overlooked epileptic syndrome presenting with a triad of eyelid myoclonia with or without absence seizures, eye closure-induced EEG paroxysms, and photosensitivity. We present a seven-year-old female who presented with eyelid myoclonia evident since birth with absence seizures and migraines with associated photosensitivity. An EEG with photic stimulation confirmed the diagnosis of Jeavons syndrome. Genetic testing showed a heterozygous mutation in the PLCB1 gene which has been linked to early onset epilepsies and encephalopathic epilepsies. This mutation and her clinical presentation identifies another etiology of Jeavons syndrome and confirms it can begin from birth. Its presence highlights the importance of genetic testing in epileptic patients to better understand the links between genetics and epilepsy syndromes so appropriate treatment can be initiated.


The influence of growth and E. coli endotoxaemia on amoxicillin pharmacokinetics in turkeys.
1. This experiment aimed to determine if the pharmacokinetics of amoxicillin (AMO) was affected by rapid growth or intravenous (i.v.) injection of Escherichia coli lipopolysaccharide (LPS). 2. Turkeys of 2.0, 5.5 and 12.0 kg were administered i.v. or orally with AMO sodium at the dose of 15 mg/kg. Another group (5.7 kg) was treated with LPS prior to i.v. AMO administration. Plasma drug concentrations were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using a non-compartmental model. To assess the haemodynamic effects of endotoxaemia, turkeys were subjected to echocardiography. 3. During growth from 2.0 to 5.5 kg, the area under the drug concentration-time curve after i.v. AMO administration increased from 9.37 ± 2.43 to 21.29 ± 5.49 mg×h/ml. Total body clearance decreased from 1.72 ± 0.55 to 0.75 ± 0.12 l/h/kg. Growth to 12.0 kg did not further affect these parameters. Mean residence time and elimination half-life gradually increased. Pharmacokinetics of orally administered drug followed a similar pattern. LPS injection affected stroke volume, heart rate and resistance index. However, it did not affect the pharmacokinetic profile of AMO in survivors. 4. It is concluded that rapid growth in turkeys affects AMO pharmacokinetics. Endotoxaemia, on the other hand, does not affect AMO elimination if compensatory mechanisms develop.


Lignan enhancement in hairy root cultures of Linum album using coniferaldehyde and methylenedioxycinnamic acid.
Feeding experiments with hairy root cultures of Linum album have established that the extracellular coniferaldehyde is a good precursor for production of two lignans: lariciresinol (LARI) and pinoresinol (PINO). The accumulation of the LARI, PINO, and podophyllotoxin (PTOX) in hairy roots were enhanced about 14.8-, 8.7-, and 1.5-fold (107.61, 8.7 and 6.42 µg g(-1) Fresh Wight), respectively, by the addition of coniferaldehyde (2 mM) to the culture media (after 24 hr). This result was correlated with an increase pinoresinol/lariciresinol reductase (PLR) expression gene and cinnamyl alcohol dehydrogenase (CAD) activity in the fed hairy roots. Adding 3,4-(methylendioxy)cinnamic acid (MDCA) precursor did not influence on the lignans accumulation, but the lignin content of the hairy roots was increased. Moreover, the expression genes of phenylalanine ammonialyase (PAL), CAD, and cinnamoyl-CoA reductase (CCR) were influenced after feeding hairy roots with MDCA.


[Effects of simvastatin on acute-phase protein levels after cardiac surgery].
There is contradictory evidence as to whether the pleiotropic effects of statins improve morbidity/mortality rates in coronary artery bypass grafting with extracorporeal circulation, as they reduce the protein plasma levels in the acute phase. This randomized prospective study included 44 patients undergoing elective coronary artery bypass grafting with extracorporeal circulation who were allocated to one of 2 groups: group A (n = 22), patients taking simvastatin, and group B, control (n = 22). The plasma levels of interleukin-6, complement 4 and C-reactive protein were determined. No significant differences were noted between the 2 groups with respect to the acute-phase protein levels, or the postoperative complications. In both groups, compared with the initial levels, interleukin-6 levels peaked at 6 h after surgery and C-reactive protein at 48 h. Complement 4 levels decreased from the start of the cardiopulmonary bypass and returned progressively toward the baseline value at 48 h after surgery. Simvastatin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass produces no significant differences in the levels of acute-phase protein.


Overweight causes left ventricular diastolic asynchrony and diastolic dysfunction: a study based on speckle tracking echocardiography in healthy subjects.
Left ventricular (LV) diastolic dysfunction is often observed in healthy subjects and can be a cause of heart failure with preserved ejection fraction (EF). We aimed to investigate the role of LV diastolic asynchrony as a cause of diastolic dysfunction in healthy subjects. In 40 healthy subjects, two-dimensional speckle tracking imaging (2DSTI) was performed to measure the peak early diastolic longitudinal strain rates (Esr) of the apical, mid-ventricular, and basal segments of the septum and posterior wall. A mean value of the Esr of the 6 segments (mEsr) was calculated. The time from aortic valve closure to the Esr was measured for each segment, and the standard deviation (SDTEsr) was calculated. The peak global early diastolic strain rate (gEsr) was measured with a region of interest (ROI) on the whole LV myocardium. LV flow propagation velocity (FPV) was measured using conventional Doppler techniques. SDTEsr was not correlated with age, but was significantly correlated with body mass index (BMI) (r = 0.41, p < 0.01). Although no significant correlation was observed between mEsr and FPV, gEsr and SDTEsr significantly correlated with FPV (r = 0.41, p < 0.01; r = -0.54, p < 0.001). As a result of the multiple regression analysis, SDTEsr was the single determinant of FPV. Diastolic asynchrony, associated with overweight but not with aging, may contribute to diastolic dysfunction in healthy subjects.


Antimicrobial susceptibility testing in the office laboratory.
The performance, quality control and interpretation of antimicrobial susceptibility tests are a complex affair. Fortunately empiric oral antimicrobial therapy usually suffices for most nonsystemic pediatric bacterial infections which would ordinarily be treated on an outpatient basis (e.g. otitis media, streptococcal pharyngitis, pyoderma, UTI). Common pediatric pathogens such as H. influenzae and S. pneumoniae require uncommon expertise and complex systems for appropriate susceptibility testing. Direct susceptibility testing of urine specimens is the only current antimicrobial test that can be practically and reliable performed in most office laboratories. Access to a reliable reference laboratory with appropriate quality control systems is essential for other antimicrobial susceptibility testing needs.


Reduced tricarboxylic acid cycle flux in type 2 diabetes mellitus?
Mitochondrial dysfunction has been postulated to underlie muscular fat accumulation, leading to muscular insulin sensitivity and ultimately type 2 diabetes mellitus. Here we re-interpret previously published data on [(13)C]acetate recovery in breath gas obtained during exercise in type 2 diabetic patients and control individuals. When infusing [(13)C]palmitate to estimate fat oxidation, part of the label is lost in exchange reactions of the tricarboxylic acid (TCA) cycle. To correct for this loss of label, an acetate recovery factor (ARF) has previously been used, assuming that 100% of the exogenously provided acetate will enter the TCA cycle. The recovery of acetate in breath gas depends on the TCA cycle activity, hence providing an indirect measure of the latter and a marker of mitochondrial function. Re-evaluation of the available literature reveals that the ARF during exercise is highest in lean, healthy individuals, followed by obese individuals and type 2 diabetic patients. Revisiting previously published findings on the ARF during exercise in type 2 diabetic patients reveals a reduction in muscular TCA cycle flux, reflecting mitochondrial dysfunction, in these patients. How mitochondrial dysfunction is related to type 2 diabetes mellitus-cause or consequence-requires further study.


Production of lymphocyte activating factor in vivo.
Mice injected with Propionibacterium acnes, when challenged with lipopolysaccharide release a range of soluble mediators into their serum. Included among these is lymphocyte activating factor (LAF, interleukin-1). The release of LAF in vivo was detected only when serum samples were assayed at high dilution because inhibitors of its activity in vitro were also present. The kinetics of release of LAF in vivo after injection of P. acnes was dependent on the mouse strain used. LAF was also detected in serum collected from nude mice, implying that the LAF activity measured in vitro was not due to contamination with T cell products, such as interleukin 2.


Electrophoretic investigation of the boron cluster anion [7-(2'-pyridyl)-nido-7,8-dicarbaundecaborate]- and its protonated zwitterionic product.
ACN is a better solvent than methanol for both [NMe(4)] [7-(2'-pyridyl)-nido-7,8-C(2)B(9)H(11)] and its protonated anion. The investigated laboratory preparations of the salt and of its protonated anion are electrophoretically pure solids stable for 2 months at 4 degrees C. At a longer storage, the solid salt is more stable than the solid protonated anion. In the 40:60 v/v water-methanol solvent, decomposition products of the salt anion are detectable after one-week storage of the salt solution at 4 degrees C. The protonated anion does not decompose for almost 1 year in water-organic solutions at 4 degrees C. The exchange of the proton between the protonated anion and the solution is reversible and fast at room temperature. The pH dependence of the mobility of the [7-(2(-pyridyl)-nido-7,8-C(2)B(9)H(11)](-) anion reveals that the basicity of the nitrogen atom in the pyridine ring is not significantly affected by the bonding of the pyridyl group to the nido-7,8-C(2)B(9)H(11) cluster in position 7 and that the proton from the solution is accepted by the nitrogen atom in the 2-pyridyl ring. The UV-spectra of the salt and of its protonated anion indicate that the accepted proton is probably slightly shifted to the open face of the nido-7,8-C(2)B(9)H(11) cluster. The [1](-) is chiral.


Controlled Structuring of Hyaluronan Films by Phase Separation and Inversion.
This work explores application of phase separation phenomena for structuring of films made from hyaluronan. A time-sequenced dispensing of different solution mixtures was applied under rotation of hyaluronan-covered substrates to generate surface textures. This method is applicable in direct surface modification or cover layer deposition. Changes in the surface topography were characterized by atomic force microscopy, optical microscopy, and contact and non-contact profilometry. The mechanical properties of the surface-modified self-supporting films were compared using a universal testing machine. Experimental results show that diverse hyaluronan-based surface reliefs and self-supporting films with improved mechanical properties can be prepared using a newly designed multi-step phase separation process without the need for sacrificial removable templates or additives.


Use of d-3He proton spectroscopy as a diagnostic of shell rho r in capsule implosion experiments with approximately 0.2 NIF scale high temperature Hohlraums at Omega.
We present the calculations and preliminary results from experiments on the Omega laser facility using d-(3)He filled plastic capsule implosions in gold Hohlraums. These experiments aim to develop a technique to measure shell rho r and capsule unablated mass with proton spectroscopy and will be applied to future National Ignition Facility (NIF) experiments with ignition scale capsules. The Omega Hohlraums are 1900 microm length x 1200 microm diameter and have a 70% laser entrance hole. This is approximately a 0.2 NIF scale ignition Hohlraum and reaches temperatures of 265-275 eV similar to those during the peak of the NIF drive. These capsules can be used as a diagnostic of shell rho r, since the d-(3)He gas fill produces 14.7 MeV protons in the implosion, which escape through the shell and produce a proton spectrum that depends on the integrated rho r of the remaining shell mass. The neutron yield, proton yield, and spectra change with capsule shell thickness as the unablated mass or remaining capsule rho r changes. Proton stopping models are used to infer shell unablated mass and shell rho r from the proton spectra measured with different filter thicknesses. The experiment is well modeled with respect to Hohlraum energetics, neutron yields, and x-ray imploded core image size, but there are discrepancies between the observed and simulated proton spectra.


Implications of Race and Ethnicity in Sarcopenia US National Prevalence of Sarcopenia by Muscle Mass, Strength, and Function Indices.
Sarcopenia prevalence varies widely by definitions and populations, which led to the creation of new criteria by the Sarcopenia Definitions and Outcomes Consortium. Yet, the degree to which sarcopenia prevalence varies according to these criteria across race and ethnic groups in the U.S. population needs further investigation. We estimated the US national prevalence of sarcopenia using different indices among adults aged 50-80 years across race and ethnicity groups utilizing data from the National Health and Nutrition Examination Surveys (NHANES: 1999-2002 and 2011-2014). Sarcopenia was defined by appendicular lean mass divided by body mass index (ALM/BMI), grip strength, and gait speed. For each index the following samples were constructed: grip strength (NHANES 2011-2014: N=4,615), gait speed (NHANES 1999-2002: N=3,448) and ALM/BMI (NHANES 1999-2002: N=3,448) among adults aged 50-80 years. Sarcopenia prevalence varied by race/ethnicity: NH-Whites (11.2-24.3%), Hispanics (21.9-36.0%), NH-Blacks (4.4-27.7%), and Asians/others (18.5-35.7%). Based on the multivariable models, compared to NH-Whites, NH-Blacks were less likely to have sarcopenia by ALM/BMI (OR=0.26, 95%CI: 0.18-0.39), and more likely by gait speed (OR=3.90, 95% CI: 3.00-5.06) with no difference by grip strength (OR=0.96, 95%CI: 0.75-1.24). While, Hispanics and Asians/others were more likely to have sarcopenia by grip strength, gait speed, and ALM/BMI (ORs=2.15-3.21) compared to NH-Whites. This study suggests the need for inclusion of race/ethnicity related criteria in sarcopenia definitions. Future investigations could determine whether this discrepancy between race/ethnicity across sarcopenia indices, particularly in NH-Blacks, is partly due to either muscle mass or functional changes with aging.


Comparison of molar intrusion efficiency and bone density by CT in patients with different vertical facial morphology.
The purpose of this study is to examine the relationship between molar intrusion efficiency and bone density in patients with different vertical facial morphology. Thirty-six female patients, with overerupted upper first molars, were divided into two groups according to mandiblular plane angle (FH-MP): hyperdivergent, FH-MP>30° (G1), hypodivergent, FH-MP<22° (G2). Mini-screw implants with elastic chains were used to intrude upper first molars. Spiral CT was used to measure the intrusion degree of upper first molar and bone density, and molar intrusion efficiency was calculated as amount/duration (mm month(-1) ). In addition, each tooth was divided into three portions (cervical, furcation and apical) to measure the bone density. It was found in this study that treatment duration was 3·13 and 4·71 months in G1 and G2 and that the intrusion efficiency was 1·57 and 0·81 in G1 and G2 with significant difference (P < 0·05). There were significant differences in cervical, furcation and apical bone density between two groups (P < 0·05). The bone density was significantly reduced after molar intrusion. In addition, the bone density change was greater in G1 than in G2 (P < 0·05). It was concluded that molars were more easily to be intruded in hyperdivergent than in hypodivergent patients. The difference of bone density and bone density changes during intrusion may account for the variation of molar intrusion efficiency.


Patient Characteristics Associated With Severe Hypoglycemia in a Type 2 Diabetes Cohort in a Large, Integrated Health Care System From 2006 to 2015.
To identify severe hypoglycemia events, defined as emergency department visits or hospitalizations for hypoglycemia, in patients with type 2 diabetes receiving care in a large health system and to identify patient characteristics associated with severe hypoglycemia events. This was a retrospective cohort study from January 2006 to December 2015 using the electronic medical record in the Cleveland Clinic Health System (CCHS). Participants included 50,439 patients with type 2 diabetes receiving care in the CCHS. Number of severe hypoglycemia events and associated patient characteristics were identified. The incidence proportion of severe hypoglycemia increased from 0.12% in 2006 to 0.31% in 2015 (P = 0.01). Compared with patients who did not experience severe hypoglycemia, those with severe hypoglycemia had similar median glycosylated hemoglobin (HbA1c) levels. More patients with severe hypoglycemia versus those without had a prior diagnosis of nonsevere hypoglycemia (9% vs. 2%, P < 0.001). Logistic regression confirmed an increased odds for severe hypoglycemia with insulin, sulfonylureas, increased number of diabetes medications, history of nonsevere hypoglycemia (odds ratio [OR] 3.01, P < 0.001), HbA1c <6% (42 mmol/mol) (OR 1.95, P < 0.001), black race, and increased Charlson comorbidity index. Lower odds of severe hypoglycemia were noted with higher BMI and use of metformin, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 agonists. In this retrospective study of patients with type 2 diabetes with severe hypoglycemia, patient characteristics were identified. Patients with severe hypoglycemia had previous nonsevere hypoglycemia diagnoses more frequently than those without. Identifying patients at high risk at the point of care can allow for change in modifiable risk factors and prevention of severe hypoglycemia events.


Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution.
Large dynamic nuclear polarization signal enhancements (up to a factor of 100) were obtained in the solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water solutions with the use of dynamic nuclear polarization. Polarization was transferred from the unpaired electrons of nitroxide free radicals to nuclear spins through microwave irradiation near the electron paramagnetic resonance frequency. This approach may be a generally applicable signal enhancement scheme for the high-resolution solid-state NMR spectroscopy of biomolecules.


Mycobacterium avium complex empyema in a patient with interferon gamma autoantibodies.
Interferon gamma (IFN-γ) autoantibodies are a relatively recently discovered clinical entity, which have been shown to be associated with disseminated non-tuberculous mycobacterial (NTM) infections and other opportunistic infections. Interestingly, isolated NTM infections (without disseminated NTM infection) have not been shown to be a good predictor of the presence of IFN-γ autoantibodies. This case describes an isolated NTM empyema in a patient with IFN-γ autoantibodies and makes the argument that the development of an NTM empyema in a patient with no known immunodeficiency should prompt consideration for IFN-γ testing. Additionally, this case underscores the importance for clinicians to recognize that an unusual infection without the typical cause of impairment in immunity should prompt a more thorough investigation of the patient's immune system.


Altered propionate metabolism contributes to tumour progression and aggressiveness.
The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. Here, we find that dysregulation of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells, increasing their metastatic potential. This occurs through the downregulation of methylmalonyl coenzyme A epimerase (MCEE), mediated by an extracellular signal-regulated kinase 2-driven transcription factor Sp1/early growth response protein 1 transcriptional switch driven by metastatic signalling at its promoter level. The loss of MCEE results in reduced propionate-driven anaplerotic flux and intracellular and intratumoral accumulation of methylmalonic acid, a by-product of propionate metabolism that promotes cancer cell invasiveness. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as an important contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas.


An Atypical and Multifactorial Acute Immune Polyradiculopathy: A Case Report.
Clinical diagnosis often focuses on identifying the single cause of a patient's symptoms but it is becoming increasingly recognized that a subset of patients exist where 2 pathological entities coexist. These patients present a particular diagnostic challenge because the first "positive" diagnostic test is not the definitive stopping point in their evaluation. Here, we present the case of a 47-year-old woman with multiple cranial neuropathies and a polyradiculopathy. A significant pleocytosis in the cerebrospinal fluid sparked a broad evaluation which revealed pathologic evidence of sarcoidosis and molecular evidence of neurofascin (NF)-155 and NF-140 antibodies. The pathogenic contribution of these 2 pathologic entities, or interaction, to this patient's case is not clear. Nevertheless, the patient responded robustly to steroids and symptoms significantly improved. This case is a demonstration of the balance between Occam's razor and Hickam's dictum in clinical practice.


The development and characterization of a 57K single nucleotide polymorphism array for rainbow trout.
In this study, we describe the development and characterization of the first high-density single nucleotide polymorphism (SNP) genotyping array for rainbow trout. The SNP array is publically available from a commercial vendor (Affymetrix). The SNP genotyping quality was high, and validation rate was close to 90%. This is comparable to other farm animals and is much higher than previous smaller scale SNP validation studies in rainbow trout. High quality and integrity of the genotypes are evident from sample reproducibility and from nearly 100% agreement in genotyping results from other methods. The array is very useful for rainbow trout aquaculture populations with more than 40 900 polymorphic markers per population. For wild populations that were confounded by a smaller sample size, the number of polymorphic markers was between 10 577 and 24 330. Comparison between genotypes from individual populations suggests good potential for identifying candidate markers for populations' traceability. Linkage analysis and mapping of the SNPs to the reference genome assembly provide strong evidence for a wide distribution throughout the genome with good representation in all 29 chromosomes. A total of 68% of the genome scaffolds and contigs were anchored through linkage analysis using the SNP array genotypes, including ~20% of the genome assembly that has not been previously anchored to chromosomes.


Higher dispersion efficacy of functionalized carbon nanotubes in chemical and biological environments.
Aqueous dispersions of functionalized carbon nanotubes (CNTs) are now widely used for biomedical applications. Their stability in different in vitro or in vivo environments, however, depends on a wide range of parameters, such as pH and salt concentrations of the surrounding medium, and length, aspect ratio, surface charge, and functionalization of the applied CNTs. Although many of these aspects have been investigated separately, no study is available in the literature to date, which examines these parameters simultaneously. Therefore, we have chosen five types of carbon nanotubes, varying in their dimensions and surface properties, for a multidimensional analysis of dispersion stability in salt solutions of differing pH and concentrations. Furthermore, we examine the dispersion stability of oxidized CNTs in biological fluids, such as cellular growth media and human plasma, and their toxicity toward cancer cells. To enhance dispersibility and biocompatibility, the influence of different functionalization schemes is studied. The results of our investigations indicate that both CNT dimensions and surface functionalization have a significant influence on their dispersion and in vitro behavior. In particular, factors such as a short aspect ratio, presence of oxidation debris and serum proteins, low salt concentration, and an appropriate pH are shown to improve the dispersion stability. Furthermore, covalent surface functionalization with amine-terminated polyethylene glycol (PEG) is demonstrated to stabilize CNT dispersions in various media and to reduce deleterious effects on cultured cells. These findings provide crucial data for the development of biofunctionalization protocols, for example, for future cancer theranostics, and optimizing the stability of functionalized CNTs in varied biological environments.


Utilisation of probiotics for disease management in giant freshwater prawn (Macrobrachium rosenbergii): Administration methods, antagonistic effects and immune response.
The giant freshwater prawn (Macrobrachium rosenbergii) is a high-yielding prawn variety well-received worldwide due to its ability to adapt to freshwater culture systems. Macrobrachium rosenbergii is an alternative to shrimp typically obtained from marine and brackish aquaculture systems. However, the use of intensive culture systems can lead to disease outbreaks, particularly in larval and post-larval stages, caused by pathogenic agents such as viruses, bacteria, fungi, yeasts and protozoans. White tail disease (viral), white spot syndrome (viral) and bacterial necrosis are examples of economically significant diseases. Given the increasing antibiotic resistance of disease-causing microorganisms, probiotics have emerged as promising alternatives for disease control. Probiotics are live active microbes that are introduced into a target host in an adequate number or dose to promote its health. In the present paper, we first discuss the diseases that occur in M. rosenbergii production, followed by an in-depth discussion on probiotics. We elaborate on the common methods of probiotics administration and explain the beneficial health effects of probiotics as immunity enhancers. Moreover, we discuss the antagonistic effects of probiotics on pathogenic microorganisms. Altogether, this paper provides a comprehensive overview of disease control in M. rosenbergii aquaculture through the use of probiotics, which could enhance the sustainability of prawn culture.


Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock.
Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function.


A taxonomic revision of the genus Thalia Blumenbach, 1798; Weelia Yount, 1954; Brooksia Metcalf, 1918 (Salpida: Salpidae) from East Coast of Peninsular Malaysia.
The marine pelagic tunicates of Family Salpidae Lahille, 1888 presence in the coastal waters of Terengganu was studied for the first time. Samples were collected from April to July 2016 using 200µm Bongo net; hauled vertically from a stationary vessel; and preserved in 5% buffered formaldehyde. A total of 4 species under this family were found, observed and identified: Thalia rhomboides (Quoy and Gaimard 1824); Thalia sibogae (van Soest 1973); Weelia cylindrica (Cuvier 1804) and Brooksia rostrata (Traustedt 1893). All species were identified as new records in Malaysian waters. The description on morphological characteristics and a key to the solitary and aggregate of the recorded species is added. The distribution was analyzed from the 18 sampling stations in theTerengganu waters including Pulau Bidong, Pulau Yu and Pulau Kapas. The collected data was then compiled with previous available global literature on the distribution and occurrence of these four species, consequently updating the biodiversity of Malaysian fauna and its worldwide biogeography distribution.


A Raman study of low frequency intrahelical modes in A-, B-, and C-DNA.
We have obtained low frequency (less than 200 cm-1) Raman spectra of calf-thymus DNA and poly(rI).poly(rC) as a function of water content and counterion species and of d(GGTATACC)2 and d(CGCGAATTCGCG)2 crystals. We have found that the Raman scattering from water in the first and second hydration shells does not contribute directly to the Raman spectra of DNA. We have determined the number of strong Raman active modes by comparing spectra for different sample orientations and polarizations and by obtaining fits to the spectra. We have found at least five Raman active modes in the spectra of A- and B-DNA. The frequencies of the modes above 40 cm-1 do not vary with counterion species, and there are only relatively small changes upon hydration. These modes are, therefore, almost completely internal. The mode near 34 cm-1 in A-DNA is mostly internal, whereas the mode near 25 cm-1 is dominated by interhelical interactions. The observed intensity changes upon dehydration were found to be due to the decrease in interhelical distance. Polymer length appears to play a role in the lowest frequency modes.


[Observation on effectiveness of fortified flour on nutrition status improvement of poor area women in Weichang County of Hebei Province in China].
To observe the effectiveness of fortified flour on nutrition status improvement of poor area women in Hebei Province. Nutrition status and dietary patterns were surveyed on 611 poor rural women in Weichang county of Hebei province for three years. Nutrient intakes of intervention group supplied with fortified flour with VA, VB1, VB2, folic acid, niacin, iron and zinc has significantly increased and its levels have achieved the Chinese DRIs after the intervension women consumed the fortified flour. The blood measurement showed that IDA prevalence of women decreased and the iron status has been improved. Serum zinc, folic acid and VA levels have significantly increased from the first to the third year after consuming the fortified flour. Fortified flour is significantly effective in improving the nutrition status in the micronutrient-deficiency women of intervention group. The nutrition status of the control group in the trial areas didn't change with the economic development. It is effective and feasible way to improve the nutrition status through consuming the fortified flour on poor areas women in northern China.


The immediate effect of kinesiology taping on muscular imbalance in the lateral flexors of the neck in infants: a randomized masked study.
To investigate the immediate effect of kinesiology taping (KT) on muscular imbalance in the lateral flexors of the neck. Randomized controlled trial. Twenty-nine infants with congenital muscular torticollis and muscular imbalance in the lateral flexors of the neck were chosen consecutively. In addition, 5 healthy infants with no signs of muscular imbalance in the neck were tested. The infants were randomly allocated to either an intervention group or a control group. The intervention group had kinesiology taping applied on the affected side using the muscle-relaxing technique. The healthy infants were tested both with and without kinesiology taping. The evaluator was blinded to whether the infants were or were not taped. There was a significant difference in the change of Muscle Function Scale (MFS) scores between the groups (P < .0001). In the intervention group, there were significantly lower scores on the affected side that had been taped (P < .0001) and also significantly higher scores on the unaffected side (P = .01). There were no significant differences in the control group. For the healthy infants, with no imbalance in the lateral flexors of the neck, there were no changes to the MFS scores regardless of whether the kinesiology tape was applied. For infants with congenital muscular torticollis, kinesiology taping applied on the affected side had an immediate effect on the MFS scores for the muscular imbalance in the lateral flexors of the neck.


A low prevalence of cystic fibrosis in Uruguayans of mainly European descent.
Cystic fibrosis is the most common hereditary disease in populations of European descent, with its prevalence depending on the populations and ethnic groups studied. In contrast to Europe and North America, there is little information about this disease in Latin America. Uruguay currently has a human population of 3,000,000, with a low rate of miscegenation and no remaining isolated Amerindian groups. In the present study, we estimated the prevalence of cystic fibrosis in this country based on the detection of DeltaF508 mutation carriers in 500 unrelated individuals and on the frequency of individuals homozygous for this mutation within the affected population. The latter was calculated from the frequency of the different mutations and genotypes observed in a sample of 52 previously described patients with confirmed cystic fibrosis. A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, our data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants).


Nocardia huaxiensis sp. nov., an actinomycete isolated from human skin.
A novel actinomycete, designated as strain WCH-YHL-001T, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001T were C16 : 0, C18 : 1 ω9c, C18 : 0 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4ω-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001T belonged to the genus Nocardia. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain WCH-YHL-001T and type strains of Nocardia species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for isDDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001T represented a novel species of the genus Nocardia, for which the name Nocardia huaxiensis sp. nov. is proposed, with the type strain WCH-YHL-001T (=GDMCC 4.181T=JCM 34475 T=NBRC 114973T).


Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic.
This study assessed clinical activity, safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma. In this open-label, multicentre, uncontrolled, Phase II study (ClinicalTrials.gov NCT00896480), patients received ≤24 doses of MAGE-A3 immunotherapeutic (4-cycle schedule). At screening, two skin lesions were biopsied for MAGE-A3 expression analysis and presence/absence of a previously identified gene signature (GS) associated with favourable clinical outcome. Clinical activity was assessed in terms of clinical response, time-to-treatment failure (TTF) and progression-free survival (PFS). Adverse events (AEs) and serious AEs (SAEs) were recorded. MAGE-A3-specific immune responses were assessed. Clinical activity and immunogenicity were analysed overall and separately in patients with 2/2 (GS+/+), 1/2 (GS+/-) or 0/2 (GS-/-) biopsies presenting GS. Of 49 screened patients, 32 had MAGE-A3-positive tumours; 24 (8 GS+/+, 8 GS+/-, 8 GS-/-) were treated. Two complete (GS+/+ patients) and two partial responses (one GS+/+, one GS+/-) were reported; of note, one of the two complete responses was unlikely to be related to the study treatment. Median TTF and PFS were 14.8 and 7.2 months for GS+/+, 2.3 and 2.8 months for GS+/- and 2.4 and 2.9 months for GS-/- patients. Three grade 3 AEs and two SAEs unrelated to treatment were reported. All patients were seropositive for MAGE-A3 antibodies on vaccination with no differences between the different GS profiles. MAGE-A3-specific CD4+ and CD8+ T cell immunogenicity was detected; 12/16 (75.0%) of patients presented CD4+ T cell responses. Treatment with MAGE-A3 immunotherapeutic showed signs of clinical activity in GS+/+ patients. Treatment was well tolerated and immunogenic. No differences in immune responses according to GS status were observed. NCT00896480 (Results).


Scaling Relations and Self-Similarity of 3-Dimensional Reynolds-Averaged Navier-Stokes Equations.
Scaling conditions to achieve self-similar solutions of 3-Dimensional (3D) Reynolds-Averaged Navier-Stokes Equations, as an initial and boundary value problem, are obtained by utilizing Lie Group of Point Scaling Transformations. By means of an open-source Navier-Stokes solver and the derived self-similarity conditions, we demonstrated self-similarity within the time variation of flow dynamics for a rigid-lid cavity problem under both up-scaled and down-scaled domains. The strength of the proposed approach lies in its ability to consider the underlying flow dynamics through not only from the governing equations under consideration but also from the initial and boundary conditions, hence allowing to obtain perfect self-similarity in different time and space scales. The proposed methodology can be a valuable tool in obtaining self-similar flow dynamics under preferred level of detail, which can be represented by initial and boundary value problems under specific assumptions.


Interventions to reduce porcine epidemic diarrhea virus prevalence in feed in a Chinese swine production system: A case study.
Research has shown that feed and feed ingredients can be one of the potential routes of transmitting viral pathogens into swine farms. In this short communication, we report two cases of Porcine Epidemic Diarrhea (PED) in two sow farms located in eastern China. Immediately after the outbreaks, extensive sampling and testing for genetic materials of PEDV was carried out on farms, and at the feed mill, in an effort to identify possible sources of infection based on field observations of local area viral spread and interventions already implemented to lower risk of this spread. Samples collected from personnel or supplies entering the farms were inspected and proved as low risk factors. In contrast, feed and feed ingredient samples collected at the on-farm feed bins, and at the feed mill, tested positive for PEDV RNA. Based on these data, multiple interventions to lower viral spread via feed were implemented including (1) simplification of diet formulation excluding high-risk ingredients, (2) extension of thermal treatment during pellet conditioning and (3) maximising feed quarantine on farm up to 7 days from feed delivery to consumption. Collectively, these interventions appeared to have a positive effect as the prevalence of PED-related disease and the number of PEDV-positive feed or feed ingredient samples decreased considerably following implementation.


Free arterialised flow-through venous flap with venous anastomosis as the outflow (A-A-V flap) for reconstruction after severe finger injuries.
Abstract For reconstruction of volar defects, an arterialised flow-through venous flap (A-A flap) can be used to restore the soft tissues and the digital artery at the same time. However, there have been reports that the circulation of this flap is inadequate. This study used a venous flap with only one venous anastomosis for the outflow of an A-A flap (A-A-V flap) to solve this problem. Six patients with defects of the finger soft tissues and digital artery after severe finger injuries were performed. The venous flap with a Y-shaped vein was harvested. The digital artery was reconstructed, after which the other proximal vein of this flap was anastomosed to the dorsal subcutaneous vein. The flap survived in all patients and histological examination of flap tissue showed a nearly normal architecture. This study describes the good results obtained with an A-A-V flap, and discusses the utility of our flap in comparison with previously reported venous flaps.


[Comparative study of the immunogenic activity of 2 vaccines from strain K against swine plague].
The comparative testing of the immunogenic activity of vaccines produced with strain K cultured in cell cultures and rabbits has revealed that one vaccinal dose of the culture vaccine for pigs contains 1 000 reactogenic doses for rabbits and about 400 immunizing doses for pigs. In a vaccinal dose for pigs of a vaccine obtained from rabbits there are 400 reactogenic doses for rabbits and 100 immunizing doses for pigs. Swine fever-affected pigs treated with a vaccine of strain K, containing more than 100 immunizing doses per vaccinal dose, develop immunity that lasts not less than 12 months. Freeze-dried vaccines of strain K can be stored at ordinary refrigerator temperature in the course of one year, and at minus 20 to 30 degrees C--in the course of two years.


Anodic oxide formation on aluminium-terbium alloys.
Aluminium terbium alloys were prepared by simultaneous thermal evaporation resulting in a thin film library covering a 5 to 25 at.% Tb compositional spread. Synchrotron x-ray diffraction (XRD) proves all of the alloys to be amorphous. Scanning electron microscopy (SEM) measurements reveal the structural changes upon increase in Tb content with the formation of small, Tb-rich segregations right before a drastic change in morphology around 25 at.% Tb. Anodic oxides were formed systematically in cyclic voltammograms using scanning droplet cell microscopy. Coulometric analysis revealed a linear thickness over formation potential behaviour with film formation factors ranging from 1.2 nm V-1 (5 at.% Tb) to 1.6 nm V-1 (25 % Tb). Electrochemical impedance spectroscopy was performed for each incremental oxidation step resulting in a linear relation between inverse capacity and formation potential with dielectric constants ranging from 8 (5 at.% Tb) to 16 (25 at.% Tb).


Implementation of treatment planning in the routine clinical procedure of regional hyperthermia treatment of cervical cancer: an overview and the Rotterdam experience.
This manuscript provides an overview in the field of hyperthermia treatment planning (HTP) in cervical cancer. Treatment planning techniques: The workflow of an HTP assisted treatment generally consists of patient imaging, tissue segmentation, model generation, electromagnetic (EM) and thermal calculations, optimisation, and clinical implementation. A main role in HTP is played by numerical simulations, for which currently a number of software packages are available in hyperthermia. To implement these simulations, accurate applicator models and accurate knowledge of dielectric and thermal parameters is mandatory. Model validation is necessary to check if this is implemented well. In the translation from HTP models to the clinic, the main aspect is accurate representation of the actual treatment situation in the HTP models. Accurate patient positioning and organ-specific segmentation can be helpful in minimising the differences between model and clinic. In the clinic, different approaches are possible: simple, i.e. target centre point (TCP) steering, often called 'target steering', or only pretreatment planning versus advanced, i.e. active HTP guided steering or image guided hyperthermia by non-invasive thermometry (NIT). The Rotterdam experience: To illustrate the implementation of HTP guided steering, the Rotterdam approach of complaint adaptive steering is elaborated, in which optimisation is adapted with increased constraints on tissues with heat-induced discomfort. Many publications on HTP show that HTP can be considered a feasible method to optimise and control a hyperthermia treatment, with the objective to enhance treatment quality and documentation. Ultimately, after overcoming the various uncertainties, this may lead to dose prescription.


Examination of the cytotoxic and embryotoxic potential and underlying mechanisms of next-generation synthetic trioxolane and tetraoxane antimalarials.
Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria.


Structure of [UO2Cl4]2- in acetonitrile.
The complex formation of uranyl UO(2)(2+) with chloride ions in acetonitrile was studied by UV-vis and U L(III) EXAFS spectroscopy. The investigations unambiguously point to the existence of a [UO(2)Cl(4)](2-) species in solution with D(4)(h)() symmetry. The distances in the U(VI) coordination sphere are U-O(ax) = 1.77 +/- 0.01 Angstroms and U-Cl = 2.68 +/- 0.01 Angstroms.


Limits of surgery for pancreatic cancer.
Pancreatic cancer patients often present in an already advanced state of disease and the therapeutic approach is an interdisciplinary challenge. Surgery is an integral part in a potentially curative setting, yet in such advanced disease surgery can reach its limits. The technical feasibility has to be weighted against potential harms and the oncological reasonableness. In locally advanced disease, limits of surgery could be pushed as evidence grew. A venous vascular tumor infiltration nowadays does not preclude patients from surgery, as venous resections can be safely performed and survival rates are not inferior to patients with standard resections. Multivisceral resections have an increased risk of morbidity and mortality, but can improve overall survival. The resection and reconstruction of tumor infiltrated arteries is technically feasible, but these procedures have a high rate of associated morbidity and mortality with an unclear oncological benefit and therefore are generally not recommended. This also holds true for intentional palliative R2-resections, which do not offer a survival benefit but decrease the quality of life and have higher morbidity and mortality rates than palliative bypass procedures. A synchronous resection of the primary tumor and intraabdominal metastases in an olgiometastatic disease only offers a questionable oncological benefit and the evidence for this approach is scarce. Therefore, surgery in a metastatic disease is generally not recommended and has to be discussed interdisciplinary on a highly individual basis.Key words: pancreatic cancer multivisceral resection staging.


Conservative treatment of Fibrous Dysplasia.
Fibrous Dysplasia (FD) is a developmental disorder of bone that can affect one bone (monostotic type) or multiple bones (polyostotic type). The disease can be associated with hyperpigmentation and endocrinological disorders. In general, FD is found in teenagers, in the second decade of life. It often involves the long bones, craniofacial bones, ribs and pelvis. Approximately 30% of monostotic FD (MFD) lesions are found in the cranial, rather facial bones. It frequently appears in the posterior region of the jaw bone and is usually unilateral. The etiology of FD is not clear but even so genetic predisposition is suspected. The diagnosis is based on radiological and histopathological examination. We present an unusual case of symptomatic FD. A 15-year-old female patient was admitted to the clinic, complaining gradually increased swelling on her left side of the mandible one year ego with severe and unusual pain at related region. The bony enlargement was extending from median mandible to the crestal marginal level. Surgical shaving and recountering of mandible through the delicate preservation of the mental nerve in the left side of mandible was carried out. The aim of this report is to present the conservative treatment as sufficient treatment modality for the treatment of FD during puberty.


Diverse voices, simple desires: a conceptual design for primary care to respond to depression and related disorders.
The World Health Organization and the World Organization of Family Doctors have called for 'doable' and 'limited' tasks to integrate mental health into primary care. Little information is provided about tasks GPs can undertake outside of guidelines that suggest to prescribe medication and refer to specialists. The reorder study aimed to gather diverse patient and community perspectives to inform the development of an effective system of depression care. Five hundred and seventy-six patients completed computer-assisted telephone interviews. Two hundred and seventy-six community stakeholders completed a modified two round Delphi. Responses were analysed to identify tasks and these were synthesised into a conceptual design. Fifteen core tasks were identified, 5 were agreed upon and a further 10 identified by each group but not agreed upon. Listen, understand and empathize, provide thorough and competent diagnosis and management, follow-up and monitor patients, be accessible and do not rush appointments and provide holistic approach and tailor care to individual needs were agreed on. Other tasks included: develop plans with patients, assess for severity and suicide risk, account for social factors, be well trained in depression care and offer a range of treatment options, appropriate and timely referral, support and reassurance, educate patients about depression, prescribe appropriately and manage medication and be positive and encouraging. The tasks form the basis of a conceptual design for developing a primary care response to depression. They fit within three domains of care: the relational, competency and systems domains. This illustrates tasks for GPs beyond prescription and referral.


Epidemiological evidence for metabolic programming in dairy cattle.
In humans, there is evidence that metabolic diseases occurring in later life arise in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions. The process by which prenatal insults lead to permanent changes in tissue structure and function, and finally to low birthweight (BW), is known as developmental programming. Poor nutrition, environmental temperature, oxygen availability and overnutrition all have been shown to significantly affect intrauterine development. Because the placenta is the organ for communication between mother and fetus, placental insufficiency invariably affects embryonic development and health in later life. In order to optimise their income, dairy farmers inseminate their nulliparous heifers at adolescent age, and subsequently strive for calving intervals not longer than 380 days. Hence, heifers are still growing and multiparous animals are still yielding large quantities of milk while pregnant. Dairy cows heavily selected for milk yield have specific endocrinological characteristics, like low peripheral insulin levels and low peripheral insulin sensitivity, both contributing to safeguard glucose for milk production. The reverse of this advanced selection is the high incidence of a wide range of metabolic diseases. Evidence from epidemiological studies is now available demonstrating that milk yield during gestation and environmental factors, such as season of pregnancy and parturition, affect both the size and the intermediary metabolism of the neonatal calf. The latter suggests that further optimisation in terms of production, reproduction, general health and longevity in the dairy sector may be feasible by taking into account environmental factors occurring during pregnancy.