Anaphylactoid reactions to methotrexate.
Methotrexate is a chemotherapeutic agent frequently utilized for the treatment of malignant, rheumatic, and pulmonary diseases. Although this agent has been extensively used for more than 45 years, there are few reports of immediate systemic hypersensitivity reactions. The reported immediate reactions include anaphylaxis, urticaria, and hepatitis. However, these reactions have been reported to occur only after some prior exposure to methotrexate. No immediate hypersensitivity reactions to methotrexate have been reported during the initial exposure. We describe two patients who developed immediate systemic hypersensitivity reactions during the initial administration of methotrexate. The clinical outcomes of two patients treated by the Hematology/Oncology department at a tertiary care military medical center are described. The National Library of Medicine in Bethesda, Maryland, was electronically searched for the literature review. Patient 1, a 30-year-old male with localized high grade osteosarcoma of the left distal femur, developed generalized pruritus, urticaria, angioedema, and pharyngeal edema within 10 minutes of receiving the initial administration of intravenous high-dose methotrexate. No other pharmaceutical agents, such as antiemetics, were found to cause symptoms on rechallenge. The severity of this reaction precluded continuation of methotrexate therapy. Patient 2, a 23-year-old male with localized high grade osteosarcoma of the right distal tibia, developed pruritus and urticaria within 30 minutes of receiving the initial administration of intravenous high dose methotrexate. This patient, like most patients with immediate hypersensitivity reactions to methotrexate, developed recurrent symptoms during rechallenge of this agent despite prophylactic premedication. Unlike prior reports in our literature, our cases demonstrate that anaphylactoid reactions can occur during the initial exposure to methotrexate. Clinicians must be prepared to treat potentially life-threatening reactions with both the initial and subsequent doses of methotrexate.


The Effect of Hydrogen Bonding and Azomethine Group Orientation on Liquid Crystal Properties in Benzylidene Aniline Compounds.
This study examines the effects of substituents and hydrogen bonding, orientations of imine linkage on the behavior of benzylidene aniline compounds as liquid crystals (LC). Compounds 4-carboxy benzylidene-4-X-aniline (X = H, F, Cl, Br, CH3, OCH3) 1a-6a were synthesized by the reaction of aniline and its substituted derivatives with 4-formylbenzoic acid. Compounds 4-X-benzylidene-4-carboxy aniline (X = H, F, Cl, Br, CH3, OCH3) 1b-6b were synthesized by the reaction of benzaldehyde and its substituted derivatives with 4-aminobenzoic acid using absolute ethanol as the solvent. Synthesized compounds were characterized by FT IR and 1H NMR spectroscopy, liquid crystal properties were inves-tigated using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) techniques. Based on the mesomorphic properties, it was proven that the compounds 2b-4b are dimorphic exhibiting a smectic and nematic phase, compounds 5b, 6b are monomorphic exhibiting a nematic phase, while compounds 1a-6a and 1b have not shown any mesophase. For compounds 1a-6a hydrogen bonding and reversing imine linkage (in comparison with compounds 1b-6b) caused the absence of their mesomorphic properties.


Endogenous interleukin-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis.
To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10(-/-)) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis. IL-10(-/-) mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10(-/-) mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages. IL-10(-/-) mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1alpha [MIP-1alpha], and MIP-1beta) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8(+) T cells were reduced and the intracerebral bacterial load was not reduced in IL-10(-/-) mice compared to WT mice. Following intraperitoneal infection, IL-10(-/-) mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.


The nursing home dining assistant program: a demonstration project.
The purpose of this study was to extend earlier research on the dining assistant (DA) federal regulation allowing trained non-nursing staff to provide feeding assistance care in nursing homes. Observations were conducted pre- and post-implementation, with periodic observations during implementation. To assess sustainability, data were analyzed at 12 months post-implementation. Results replicated previous findings: DAs spent more time assisting residents, and the quality of care was comparable to that of nurse aides. Results confirmed continuation of the program at 12 months post-implementation. DA programs that augment nursing home staffing levels offer a feasible way to improve feeding assistance care within the constraints of existing resources.


Cardiovascular disease risk in women with premature ovarian insufficiency: A systematic review and meta-analysis.
The purpose of this review was to assess the relationship between premature ovarian insufficiency (POI), defined as natural menopause <40 years, and risk of ischaemic heart disease (IHD), stroke and overall cardiovascular disease (CVD). We performed a systematic search in PubMed (1966-2012), EMBASE (1980-2012). Studies were included if they were prospective, follow-up>3 years, assessment of age menopause <40 years, and incident cases of fatal or nonfatal IHD, stroke, or overall CVD. Relative risks (RRs) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 10 observational studies were identified, comprising 190,588 women (follow-up 4-37 years) with 9440 events (2026 events for IHD (seven studies) and 6438 events for stroke (seven studies) and 976 for total CVD (two studies). POI was assessed by questionnaire and incident cases through certification and event registers. POI was related to an increased risk of developing or dying from IHD (hazard ratio (HR) 1.69, 95% CI 1.29-2.21, p = 0.0001) and total CVD (HR 1.61, 95% CI 1.22-2.12, p = 0.0007). No relation was found for stroke (HR 1.03, 0.88-1.19, p = 0.74). We found no evidence for heterogeneity. POI is an independent though modest risk factor of IHD and overall CVD but not of stroke. Because of the limited impact of POI on CVD risk compared to classical cardiovascular risk factors, it is unlikely that POI will be implemented as modifier of cardiovascular risk classification.


Burnout and Appreciation: A Cross-Sectional Study Assessing Preferences for Appreciation Among Oncology Clinicians.
Feeling appreciated is related to increased well-being/reduced burnout. We developed a health care-specific appreciation assessment for clinicians, exploring what impactful appreciation looks like and whether it differs across a diverse provider population. The cross-sectional study was conducted with a diverse oncology clinician population in academic medicine as part of a general well-being survey. A total of 28 different methods of appreciation were assessed for their impact on feeling appreciated. A total of 405 clinicians participated (response rate, 58%). No single method of appreciation showed high/low impact for everyone, although seven methods received high impact ratings from 60% or more, including inclusion in decision making (76%), private words of affirmation (64%), positive feedback about skills (63%), positive comments about clinical care from patients/families (62%), efforts to reduce daily frustrations (62%), signs of trust in medical skills (62%), and time for self-care (62%). The least impactful methods of appreciation describe public expression of accomplishments, leadership rounding, and awards but each still receive a rating of moderate/high impact from 33% of participants. Appreciation comes from many different places and takes on multiple forms, suggesting that making healthcare workers (HCWs) feel valued takes the efforts of colleagues, leaders, the system as well as patients. There exists no one perfect way of showing appreciation, and no one method is meaningless for all. The impact on feeling valued is primarily a function of the specific appreciation method and not the demographic/personal characteristics of the recipient. The findings highlight modifiable factors that-when intervened upon-can reduce burnout and address organization-level determinants of burnout impactfully.


Treatment of Femoral Head Necrosis With Bone Marrow Mesenchymal Stem Cells Expressing Inducible Hepatocyte Growth Factor.
Our study assessed the effect of bone marrow mesenchymal stem cells (BMSCs) expressing inducible hepatocyte growth factor (HGF) on the recovery of femoral head necrosis (FHN). BMSCs were isolated by density gradient centrifugation. A recombinant AdTRE-HGF was constructed as the response plasmid and Adeno-X Tet-on as the regulator vector. The regulator and the response vectors were coinfected into BMSCs and induced at 0, 200, 500, 1000, and 1200 ng/mL doxycycline (Dox). After 3 days, the concentration of HGF was determined using enzyme-linked immunosorbent assay. Forty rabbits were selected to establish the FHN model and divided into 4 experimental groups. After the rabbits were killed by ketamine overdose, the restoration of FHN was assessed. The distribution of HGF-positive cells was observed by immunohistochemical method. Enzyme-linked immunosorbent assay results showed that 1000 ng/mL Dox induced the highest HGF expression level, even higher than the 1200 ng/mL Dox induction. The highest osteonecrosis incidence and empty lacunae percentage were found in group A compared with all the other groups (all P < 0.05). Furthermore, dramatically lower osteonecrosis incidence and empty lacunae percentage were found in group C compared with those of groups B and D (all P < 0.05). A significantly higher level of HGF protein was detected in group C compared with the other groups (all P < 0.05). Our study successfully developed the AdTRE-HGF, a recombinant adenovirus carrying HGF gene, for high expression of HGF in BMSCs. Importantly, introduction of BMSCs expressing HGF successfully produced the desired therapeutic effect in reversing FHN, in a Dox-dependent manner.


Competitive Stereocomplexation and Homocrystallization Behaviors in the Poly(lactide) Blends of PLLA and PDLA-PEG-PDLA with Controlled Block Length.
Stereocomplex poly(lactide) (PLA) was obtained by solution blending of linear PLLA and PDLA-PEG-PDLA. Effects of the L/D ratios, PEG block, and PDLA block on stereocomplexation of the blends are systemically discussed. The full stereocomplex PLA can be acquired by solution blending when L/D ratios are in the range of 7/3⁻5/5. The experiment results demonstrated that the stereocomplex degree of PLLA/PDLA-PEG-PDLA prepared by melt blending was closely related to the PEG block and PDLA block. POM results indicated that the blends with high L/D ratio showed large disordered spherulites, and the typical Maltese cross pattern was observed as the L/D ratios decreased. The results of PEG block on the stereocomplexation of PLLA/PDLA-PEG-PDLA revealed that the PEG blocks possessed two sides: accelerating agent for the mobility of polymer chains and decreasing nucleation capacity due to their diluting effect. The effect of PDLA block on the stereocomplexation of the blends was also well investigated. The results showed that the crystallization of sc-crystallites and hc-crystallites in the PLLA/PDLA-PEG4k-PDLA blends with different PDLA blocks presents an obvious competition relationship, and this is not beneficial to the formation of sc-crystallites with increasing PDLA block. The melting behavior of PLLA/PDLA-PEG4k-PDLA with different PDLA blocks after isothermal crystallization showed that the blends could achieve full stereocomplex when the crystallization temperature exceeded 160 °C, and a crystallite with high perfection could be formed as the crystallization temperature increased. This study systemically investigated the effects of the L/D ratios, PEG block, PDLA block, and crystallization conditions on stereocomplex crystallization of PLLA/PDLA-PEG-PDLA blends, which can provide potential approaches to control the microstructure and physical performances of PLLA/PDLA-PEG-PDLA blends.


[Dynamic changes of forest landscape pattern in Lushuihe Forest Bureau of Changbai Mountains, northeast China].
Based on the forest management inventories in Lushihe Forest Bureau of Changbai Mountains in 1987, 1995 and 2003, and by using ArcGIS and Fragstats spatial analysis software, this paper analyzed the relationships between landscape pattern change and forest management mechanism in the study area at landscape and patch scales. During the study period, the landscape fragmentation degree and heterogeneity in the study area increased. From 1987 to 2003, the patch number increased by 979, while the proportion of the largest patch area decreased from 28. 7% to 12.7%. With the change of management strategy, the landscape matrix changed from mixed broad-leaved forest matrix in 1987 to compound matrix in 1995. The extent of landscape fragmentation in 1995-2003 was somewhat reduced, compared with that in 1987-1995. During the study period, the mean patch area and edge density of broadleaved mixed forest decreased most, suggesting that natural secondary forest suffered most from human disturbances.


Purification and Properties of Mesophyll and Bundle Sheath Cell alpha-Glucan Phosphorylases from Zea mays L. : Equivalence of the Enzymes with the Cytosol and Plastid Phosphorylases from Spinach.
Two major alpha-glucan phosphorylases (I and II) from leaves of the C(4) plant corn (Zea mays L.) were previously shown to be compartmented in mesophyll and bundle sheath cells, respectively (C Mateyka, C Schnarrenberger 1984 Plant Sci Lett 36: 119-123). The two enzymes were separated by chromatography on DEAE-cellulose and purified to homogeneity by affinity chromatography on immobilized starch, according to published procedures, as developed for the cytosol and chloroplast phosphorylase from the C(3) plant spinach. The two alpha-glucan phosphorylases have their pH optimum at pH 7. The specificity for polyglucans was similar for soluble starch and amylopectin, however, differed for glycogen (K(m) = 16 micrograms per milliliter for the mesophyll cell and 250 micrograms per milliliter for the bundle sheath cell phosphorylase). Maltose, maltotriose, and maltotetraose were not cleaved by either phosphorylase. If maltopentaose was used as substrate, the rate was about twice as high with the bundle sheath cell phosphorylase, than with the mesophyll cell phosphorylase. The phosphorylase I showed a molecular mass of 174 kilodaltons and the phosphorylase II of 195 kilodaltons for the native enzyme and of 87 and of 53 kilodaltons for the SDS-treated proteins, respectively. Specific antisera raised against mesophyll cell phosphorylase from corn leaves and against chloroplast phosphorylase from spinach leaves implied high similarity for the cytosol phosphorylase of the C(3) plant spinach with mesophyll cell phosphorylase of the C(4) plant corn and of chloroplast phosphorylase of spinach with the bundle sheath cell phosphorylase of corn.


Phytochrome mediated regulation of sucrose phosphate synthase activity in maize.
The extractable activity of sucrose phosphate synthase was determined in etiolated seedlings of maize (Zea mays L.), soybean (Glycine max [L.] Merr.), and sugar beet (Beta vulgaris L.) following treatments of changing light quality. A 30-minute illumination of 30 microeinsteins per square meter per second white light produced a three-fold increase in sucrose phosphate synthase activity at 2 hours postillumination when compared to seedlings maintained in total darkness. Etiolated maize seedlings treated with 3.6 microeinsteins per square meter per second of red and far-red light showed a 50% increase and a 50% decrease in sucrose phosphate synthase activity, respectively, when compared to etiolated maize seedlings treated with white light. Maize seedlings exposed for 30 minutes to red followed by 30 minutes to far-red showed an initial increase in sucrose phosphate synthase activity followed by a rapid decrease to control level. Neither soybean or sugar beet sucrose phosphate synthase responded to the 30-minute illumination of white light. Phytochrome is involved in sucrose phosphate synthase regulation in maize, whereas it is not responsible for changes in sucrose phosphate synthase activity in soybean or sugar beet.


Characterizing the metabolism of Dehalococcoides with a constraint-based model.
Dehalococcoides strains respire a wide variety of chloro-organic compounds and are important for the bioremediation of toxic, persistent, carcinogenic, and ubiquitous ground water pollutants. In order to better understand metabolism and optimize their application, we have developed a pan-genome-scale metabolic network and constraint-based metabolic model of Dehalococcoides. The pan-genome was constructed from publicly available complete genome sequences of Dehalococcoides sp. strain CBDB1, strain 195, strain BAV1, and strain VS. We found that Dehalococcoides pan-genome consisted of 1118 core genes (shared by all), 457 dispensable genes (shared by some), and 486 unique genes (found in only one genome). The model included 549 metabolic genes that encoded 356 proteins catalyzing 497 gene-associated model reactions. Of these 497 reactions, 477 were associated with core metabolic genes, 18 with dispensable genes, and 2 with unique genes. This study, in addition to analyzing the metabolism of an environmentally important phylogenetic group on a pan-genome scale, provides valuable insights into Dehalococcoides metabolic limitations, low growth yields, and energy conservation. The model also provides a framework to anchor and compare disparate experimental data, as well as to give insights on the physiological impact of "incomplete" pathways, such as the TCA-cycle, CO(2) fixation, and cobalamin biosynthesis pathways. The model, referred to as iAI549, highlights the specialized and highly conserved nature of Dehalococcoides metabolism, and suggests that evolution of Dehalococcoides species is driven by the electron acceptor availability.


Targeted Therapy for Colorectal Cancers With Non-V600 BRAF Mutations: Perspectives for Precision Oncology.
BRAF mutations are found in up to 10% of colorectal cancers (CRC). Whereas the majority of BRAF mutant CRCs harbor V600 mutations, up to 25% express non-V600 BRAF mutations. It has been established that BRAF V600E mutations in CRC predict unresponsiveness to epidermal growth factor receptor (EGFR) inhibition-cetuximab and/or panitumumab-as a result of the constitutive activation of the mitogen-activated protein kinase pathway downstream of EGFR signaling. As more centers begin using next-generation sequencing assays to detect BRAF mutations, oncologists are more frequently confronted with treating patients with non-V600 BRAF mutations. In many instances, clinicians may be hesitant to use EGFR inhibitors for these patients, as it is largely assumed that tumors with non-V600 BRAF mutations activate the mitogen-activated protein kinase pathway in a similar manner to RAS or BRAF V600E mutations and would therefore be equally refractory to EGFR inhibition; however, the evidence that currently exists to substantiate this claim is mixed and incomplete. Recent data demonstrate that non-V600 BRAF mutant CRC is a distinct clinical entity with a favorable prognosis compared with CRC with V600E mutations. Preclinical data and several case reports suggest that a subset of BRAF non-V600 mutations that impair the protein's kinase activity may in fact confer heightened sensitivity to EGFR inhibition because of dependency on upstream receptor tyrosine kinase signaling. This review summarizes the clinical characteristics and targeted therapy approaches for non-V600 BRAF mutant CRCs, speculates on the value of non-V600 BRAF mutations as predictive biomarkers of responsiveness to EGFR inhibitors, and highlights outstanding questions in this emerging area of precision oncology.


Just data? Solidarity and justice in data-driven medicine.
This paper argues that data-driven medicine gives rise to a particular normative challenge. Against the backdrop of a distinction between the good and the right, harnessing personal health data towards the development and refinement of data-driven medicine is to be welcomed from the perspective of the good. Enacting solidarity drives progress in research and clinical practice. At the same time, such acts of sharing could-especially considering current developments in big data and artificial intelligence-compromise the right by leading to injustices and affecting concrete modes of individual self-determination. In order to address this potential tension, two key elements for ethical reflection on data-driven medicine are proposed: the controllability of information flows, including technical infrastructures that are conducive towards controllability, and a paradigm shift towards output-orientation in governance and policy.


Oncogene or Tumor Suppressor: The Coordinative Role of Lysine Methyltransferase SET7/9 in Cancer Development and the Related Mechanisms.
SET7/9 is a member of the protein lysine methyltransferase family that methylates both histone 3 lysine 4 (H3-K4) and lysine(s) of other non-histone proteins. In recent years, dis-regulation of SET7/9 were frequently detected in various cancer types and SET7/9-mediated methylation has been recognized as an important mechanism that affects cancer initiation and development through regulation of a series of cellular processes. Here we review the currently identified histone and non-histone protein targets of SET7/9 that are closely correlated with human cancer and the function of SET7/9 in regulating the expression and stability of its protein targets. The review also discusses the putative role of SET7/9 as an oncogene or tumor suppressor in the development of various cancer types and the underlying mechanisms, which may help better evaluate the potential of SET7/9 as a novel candidate for cancer therapy.


An overview on stem cell research: a report on the 7th Annual Meeting of the International Society for Stem Cell Research.
The focus of the seventh annual meeting of the International Society for Stem Cell Research was placed on several topics, such as cancer stem cells, stem cell transplantation, tissue regeneration, biology of embryonic and adult stem cells of various species and production of induced pluripotent stem cells via reprogramming of mammalian somatic cells. This report provides an overview of stem cell research, based on the proceedings of the meeting.


Pasteurella pneumotropica isolated from bone and joint infections.
Pasteurella pneumotropica is a normal inhabitant of the oropharynx of mice, rats, cats, and dogs. We describe here the first reported case of joint and bone involvement in a human. The need for culturing and adequate prophylactic treatment is discussed.


Diurnal variation of QT dispersion in patients with and without coronary artery disease.
QT dispersion defined as interlead QT variability in a 12-lead electrocardiogram was proposed by Day and associates as a simple method to evaluate the repolarization heterogenicity of the ventricular myocardium. The frequency of onset of myocardial infarction and sudden death has been reported to have a circadian variation, with a peak incidence in the early morning hours. The authors investigated whether there is diurnal variation of QT interval and QT interval dispersion in healthy subjects and in patients with coronary artery disease. The study population consisted of two groups. Group I consisted of 62 subjects without coronary artery disease and group II consisted of 82 patients with coronary artery disease. Twelve-lead ECG was recorded for each patient in the morning (between 7 AM and 8 AM), afternoon (between 3 PM and 5 PM) and at night (between 11 PM and 1 AM), on the day after performance of coronary angiography. QTc dispersion was significantly higher in patients with coronary artery disease than in healthy subjects in the morning hours and afternoon (p<0.001). Although the differences were much prominent in group I than group II, both QTc dispersion of morning and afternoon were significantly greater than those at night. There were no statistically significant differences between group I and group II at nighttime with respect to maximum QTc, minimum QTc intervals, and QTc dispersion (p>0.05). In conclusion, QT dispersion shows diurnal variation with an increase in the morning hours in both patients with coronary artery disease and subjects without coronary artery disease. The mechanism of diurnal variation of QT dispersion in patients with coronary artery disease is quite different from that of healthy subjects.


Pollen diversity and its implications to the systematics of mimosaceous species by LM and SEM.
In this study we have discussed pollen morphology of 14 mimosaceous species belonging to five genera by using light microscopy (LM) and scanning electron microscopy (SEM). The palynological features of species were determined by both qualitative and quantitative characters. The qualitative characters include pollen shape, colpi arrangement, and exine sculpturing. Oblate spheroidal shaped pollens were noted in Albizia procera, Albizia lebbeck, Acacia tortilis, Acacia ampliceps, and Acacia modesta, subprolate shaped pollen in Leucaena leucocephala, Prosopis julifera, and Acacia nilotica, prolate pollen in Acacia farnesiana and Prosopis glandulosa while spheroidal, sub spheroidal and sub oblate pollen grains were observed in Acacia catechu, Mimosa himalayana, Prosopis cineraria, respectively. Sparsely foveolate, reticulate, scabrate, and scrobiclate exine sculpturing were observed. Colpi with sunken ornamentation were seen in P. cineraria, P. glandulosa, P. juliflora, and L. leucocephala while colpi were absent in rest of the studied species. The quantitative characters were statistically studied using SPSS software. The current study gives important morpho-palynological characters for identifying and validation of close related and similar taxa which will aid to the phylogenetic analysis of Mimosaceae family.


World's Oldest Case of Synchronous Bilateral Benign Phyllodes Tumors of the Breast: A Rare Occurrence.
Phyllodes tumors are rare fibroepithelial tumors of the breast. They account for less than 0.5% of breast cancers. Bilateral presentation is a rare event, and seems to be associated with the more benign subtype but, reports are scarce. It is more common to have multiple ipsilateral tumors or bilateral asynchronous presentations. However, bilateral synchronous phyllodes are seldom reported. A literature search has revealed only five cases of synchronous and one case of metachronous bilateral phyllodes tumor of the breast. The age ranges of these patients are between 16-42 years. We are reporting the world's first case of bilateral synchronous phyllodes tumor of the breast in a patient over the age of 50 years.


Decentralization and health system performance - a focused review of dimensions, difficulties, and derivatives in India.
One of the principal goals of any health care system is to improve health through the provision of clinical and public health services. Decentralization as a reform measure aims to improve inputs, management processes and health outcomes, and has political, administrative and financial connotations. It is argued that the robustness of a health system in achieving desirable outcomes is contingent upon the width and depth of 'decision space' at the local level. Studies have used different approaches to examine one or more facets of decentralization and its effect on health system functioning; however, lack of consensus on an acceptable framework is a critical gap in determining its quantum and quality. Theorists have resorted to concepts of 'trust', 'convenience' and 'mutual benefits' to explain, define and measure components of governance in health. In the emerging 'continuum of health services' model, the challenge lies in identifying variables of performance (fiscal allocation, autonomy at local level, perception of key stakeholders, service delivery outputs, etc.) through the prism of decentralization in the first place, and in establishing directed relationships among them. This focused review paper conducted extensive web-based literature search, using PubMed and Google Scholar search engines. After screening of key words and study objectives, we retrieved 180 articles for next round of screening. One hundred and four full articles (three working papers and 101 published papers) were reviewed in totality. We attempted to summarize existing literature on decentralization and health systems performance, explain key concepts and essential variables, and develop a framework for further scientific scrutiny. Themes are presented in three separate segments of dimensions, difficulties and derivatives. Evaluation of local decision making and its effect on health system performance has been studied in a compartmentalized manner. There is sparse evidence about innovations attributable to decentralization. We observed that in India, there is very scant evaluative study on the subject. We didn't come across a single study examining the perception and experiences of local decision makers about the opportunities and challenges they faced. The existing body of evidences may be inadequate to feed into sound policy making. The principles of management hinge on measurement of inputs, processes and outputs. In the conceptual framework we propose three levels of functions (health systems functions, management functions and measurement functions) being intricately related to inputs, processes and outputs. Each level of function encompasses essential elements derived from the synthesis of information gathered through literature review and non-participant observation. We observed that it is difficult to quantify characteristics of governance at institutional, system and individual levels except through proxy means. There is an urgent need to sensitize governments and academia about how best more objective evaluation of 'shared governance' can be undertaken to benefit policy making. The future direction of enquiry should focus on context-specific evidence of its effect on the entire spectrum of health system, with special emphasis on efficiency, community participation, human resource management and quality of services.


Somatostatin analogues for somatostatin-receptor-mediated radiotherapy of cancer.
The aim of the present study was to selectively target a beta-emitter-labelled octreotide analogue to somatostatin (SRIF)-receptor-expressing tumours and to evaluate the feasibility of SRIF-receptor-mediated radiotherapy by delivering a lethal dose of radiation to the tumour. The most promising compound in a series of DTPA-coupled octreotide analogues was DTPA-benzyl-acetamido-D-Phe1, Tyr3-octreotide (SDZ413). In vitro, SDZ413 binds with nanomolar affinity to SRIF-receptors (IC50 = 4.0 nM) and inhibits growth hormone release from primary cultures of rat pituitary cells with an IC50 of 7.2 nM. Biodistribution studies with [90Y]SDZ413 demonstrated a fast and significant SRIF-receptor-specific accumulation of the labelled conjugate (tumour/muscle ratio after 24 h: 52/1). [90Y]SDZ413 was effective in the radiotherapy of SRIF-receptor-positive tumours in a nude mouse model. A single treatment with [90Y]SDZ413 led to a significant decrease (25%) of tumour mass. This effect was mediated by the intact radioligand, since treatment with [90Y]SDZ978, a derivative of SDZ413 which does not bind with high affinity to SRIF-receptors or with the unlabelled SDZ413 alone, failed to affect tumour growth. These results suggest that receptor-targeted radiotherapy with a 90Y-labelled octreotide analogue represents a new strategy for the treatment of SRIF-receptor-positive tumours that have been previously diagnosed with OctreoScan111 (pentetreotide).


Identification and quantification of thymol metabolites in plasma, liver and duodenal wall of broiler chickens using UHPLC-ESI-QTOF-MS.
In the present study, we aimed to develop a method for thymol sulfate and thymol glucuronide determination in plasma, liver and duodenal wall of broiler chickens after feeding with a Thymus vulgaris essential oil at the different concentrations (0.01, 0.05 and 0.1% w/w). UHPLC coupled with accurate-mass QTOF-MS was used for identification and quantification of thymol metabolites. Novel Waters Oasis Prime HLB solid-phase extraction cartridges were applied to sample clean-up with extraction recoveries ranged from 85 to 92%. The presence of thymol glucuronide was confirmed by MS software according to molecular formula, score, mass error and double bond equivalent. In terms of validation, calibration curves of thymol sulfate were constructed in matrix samples with linearity from 3.91 to 250.0 ng/mL and correlation coefficients were within the range of 0.9979-0.9995. Limits of detection were 0.97, 0.29 and 0.63 ng/mL and limits of quantification were 3.23, 0.97 and 2.09 ng/mL for plasma, liver and duodenal wall, respectively. Intra-day and inter-day precision expressed as relative standard deviation were <4.35%. To highlight, thymol metabolites were directly detected for the first time in liver and duodenal wall and this method was shown to be successfully applicable for investigation of thymol metabolism in chickens after thyme essential oil ingestion.


Experiences of foot and ankle mobilisations combined with home stretches in people with diabetes: a qualitative study embedded in a proof-of-concept randomised controlled trial.
The benefits of exercise and staying active are widely reported in the literature, however adherence and engagement with exercise amongst people with long-term illness and diabetes is poor. Physiotherapy aims to promote independence and physical activity using a range of strategies, including manual therapy and education/advice on exercises. However, low adherence impacts negatively on treatment outcomes. In this study, the practicality of physiotherapy interventions in patients who participate in a proof-of-concept (PoC) randomised controlled trial (RCT) will be considered. To explore the experiences of people with diabetes who received an intervention package of foot and ankle mobilisations combined with home stretches for a 6-week period. An embedded qualitative study in a proof-of-concept RCT using semi-structured interviews and thematic analysis. Purposive sample of 16 participants (mean age 73 years) with a diagnosis of diabetes (mean duration 13.4 years) were recruited. Analysis revealed seven themes informing the adherence and non-adherence to the exercise intervention. Themes describing the positive experiences were: 1) support from others to do the exercises; 2) psychological factors to motivate exercise adherence; 2) physical factors contributing to exercise adherence; 4) acceptability of home exercises during and beyond the study. Other themes described barriers: 5) social factors that contributed to exercise disengagement; 6) emotional limitations that influence exercise avoidance; 7) physical circumstances that made exercise participation burdensome. Themes highlighted positive influences by physiotherapists, the motivation of doing exercises while participating in a study, improving the perceived range of motion in their foot and ankle and reducing discomfort in these joints whilst being more active with daily activities. Our findings highlighted that the intervention of foot and ankle mobilisations combined with home stretches is feasible for study participants. Psycho-social support, self-efficacy, and physiotherapy support are motivational to adhere to the study intervention and might contribute to the success of a full-scale RCT.


A dipstick, dot-ELISA assay for the rapid and early detection of bladder cancer.
A mouse monoclonal antibody (CK1K10) specific for keratin was developed. Enzyme immunoassays (EIAs) were performed to detect keratin in urine samples using CK1K10 and anti-mouse IgG. A high degree of sensitivity and specificity was obtained in the detection of bladder cancer patients. A fast dot-ELISA was developed in which urine is applied onto nitrocellulose (NC) sheets or dipsticks. Dipsticks coated with urine samples can be stored at room temperature for more than 5 days and at -20 degrees C for more than 3 months without loss of efficiency. A high positive correlation was found between the fast dot-ELISA and other EIAs. The assay does not require sophisticated equipment nor highly trained technical staff and can be performed in less than 30 min. The keratin dot-ELISA could be a reliable screening test for the early detection of bladder cancer.


[Diabetic osteopahty and vitamin K].
Diabetes mellitus is considered as a risk factor for fractures, and there are some reports showing that metabolic effects of poor glycemic control resulted in lower bone turnover. Previous studies have revealed that this reduction of bone turnover increases bone fragility, independently of bone mineral density, so that the mechanisms of diabetic osteopahty seem to be more closely related to bone quality than bone quantity. The mechanisms of the preventive effect on fractures by vitamin K treatment should be related to amelioration of bone quality via increasing amounts of carboxylated osteocalcin. Therefore, administration of vitamin K(2) (menatetrenone) to the patients with diabetic osteopathy will be beneficial in order to improve the impaired bone quality and to reduce fracture risk.


Sjögren's syndrome presenting as hypokalemic periodic paralysis.
We describe a 21-year-old Hispanic woman who presented with hypokalemic paralysis as the initial manifestation of Sjögren's syndrome (SS). Our review of the English literature revealed 12 previously reported cases of SS and renal tubular acidosis (RTA). Paralysis often preceded the sicca complex in those patients. Renal function in the patients with hypokalemic paralysis was reduced compared with that in patients who had primary SS and RTA but no history of hypokalemic paralysis (P < 0.002). Hypokalemic periodic paralysis is a rare manifestation of SS. It is seen more often in patients with primary SS, may precede the classic sicca complex, and may serve as a clinical marker for more severe renal disease in patients who have primary SS and RTA.


The taxonomic revision of Asian Aristolochia (Aristolochiaceae) V: two new species from Yunnan, China.
Aristolochia pseudoutriformis X.X.Zhu & J.S.Ma, sp. nov. and A. yangii X.X.Zhu & J.S.Ma, sp. nov., two new species from Yunnan, China, are described and illustrated here. The former is morphologically similar to A. utriformis and A. forrestiana and the latter is similar to A. cucurbitoides and A. forrestiana. According to Ma's (1989a) classification, both new species belong to Aristolochia subgenus Siphisia on the basis of the 3-lobed gynostemium and oblong anthers that are adnate in pairs, opposite the gynostemium lobes. Meanwhile, the two new species are assessed as Vulnerable (VU D2) according to IUCN Red List criteria.


Validation of right and left ventricular conductance and echocardiography for cardiac function studies.
Continuous estimation of left ventricular volume from instantaneous conductance has compared favorably with "gold standards," is less labor intensive, and provides real-time data. Little information exists, however, correlating right ventricular conductance with such gold standards or examining the effects of an electrical field generated in the opposite ventricle. In open-chested sheep, right and left ventricular conductance, two-dimensional echocardiography, and thermodilution cardiac outputs were measured at steady-state conditions. After these measurements, postmortem pressure-volume relations, ventricular mass, and ventricular casting were performed. The corrected end-diastolic volume measured by conductance correlated well with volumes measured by echocardiography (r = 0.89), postmortem pressure-volume relations (r = 0.84), and casts (r = 0.85). Left ventricular end-diastolic volume measured by conductance did not differ significantly from other standards by analysis of variance. The presence of an electrical field in the opposite ventricle did not affect measured conductance in the studied ventricle. Conductance is useful for the measurement of right and left ventricular end-diastolic volumes in the beating heart and is not affected by the presence of an electrical field in the opposite ventricle. Hence, conductance is a useful tool in studies involving interventricular dependence and function.


Partial Sequence Analysis of the 5S to 18S rRNA Gene Region of the Maize Mitochondrial Genome.
The nucleotide sequence has been determined for a 664-base pair region of maize (Zea mays L.) mtDNA which contains the 3' end of the 18S rRNA gene, the 5S rRNA gene, and an intergenic region of 108 base pairs. Specific regions of the 18S rRNA gene show striking homology with the corresponding gene in Escherichia coli.


Cryoprecipitate production: the use of additives to enhance the yield.
Cryoprecipitate is still widely used to treat hemophilia A in developing countries. However, the yield of factor VIII is relatively low averaging, i.e. only 50%. We have attempted to enhance the yield by adding sodium citrate to the plasma following the method of Shanbrom and Owens (Blood 98, 2001, 60a). Fresh-frozen plasma (FFP) units were processed either as control plasma or after the addition of 10% sodium citrate. Cryoprecipitate was produced from both. After resuspension, calcium chloride was added to the citrated cryoprecipitate to correct for excess citrate prior to testing. The levels of FVIII and fibrinogen were determined in both preparations. The citrated cryoprecipitates had varying yields of fibrinogen and FVIII in the cryoprecipitate. The FVIII levels varied from 34% to 215% recovery. Fibrinogen ranged from 55.5% to 121.4%. We found that the addition of increasing amounts of CaCl2 to normal plasma raised the FVIII values from 1.0 to 4 U/ml. To determine the possibility of assay influence we added different quantities of CaCl2 to control plasma and measured the FVIII and activated partial thromboplastin time levels. Addition of citrate to plasma resulted in an increased total amount of cryoprecipitate much of which was citrate. Assays showed considerable ranges in the quantity of FVIII and fibrinogen. Activation of FVIII can be caused by addition of excess calcium.


Cardiovascular risk factors: multiple interventions in man.
Cardiovascular disease, especially coronary heart disease, is multifactoral. Therefore, it is reasonable to use multiple interventions to try to obtain the greatest reduction in risk. This has been attempted in several controlled clinical trials and in two community educational trials. The results have been variable, showing either benefit or a favorable trend with no statistically significance change. Although the benefit of multiple intervention has not been conclusively demonstrated, there has been a downward trend in cardiovascular mortality in many countries which parallels a downward trend in the level of cardiovascular risk, supporting the concept of benefit from multiple intervention.


Effects of polyamines on the release of gonadotropin-releasing hormone and gonadotropins in developing female rats.
Polyamines, putrescine (PUT), spermidine (SPD), spermine (SPM), and agmatine (AGM), are polycationic amines related to multiple cell functions found in high concentrations during the development of hypothalamus and pituitary. In previous works, we demonstrated that alpha-difluoromethylornithine (DFMO), an inhibitor of polyamines biosynthesis, induced a delay in puberty of female rats, accompanied by high, sustained follicle-stimulating hormone (FSH) levels during the infantile period. Also, DFMO treatment induced changes in polyamine concentration both in hypothalamus and pituitary of rats, mainly a decrease of PUT and SPD, an increase in SPM, and no change in AGM. In the present work, we investigated the direct effects of polyamines on the secretion of hypothalamic GnRH and pituitary gonadotropins in 6- and 15-day-old female rats. In 6-day-old animals, in vitro incubations with PUT, SPD, and AGM of hypothalami or anterior pituitaries were able to inhibit GnRH, FSH, and leutinizing hormone (LH) secretion, respectively. SPM showed a nonspecific transient inhibitory effect on FSH. When challenged with either high K(+) (hypothami) or GnRH (pituitaries), the tissues incubated in the presence of polyamines showed no differences when compared with their controls. No effects of polyamines in 15-day-old rats in either tissue were observed. Pituitary cell cultures of 6-day-old animals incubated with DFMO for 4 days showed a significant increase in FSH, but not in LH. We conclude that high PUT, SPD, and AGM levels during the first 10 days of life are important for the development of the hypothalamic-hypophyseal unit, probably related to an inhibitory effect on GnRH and gonadotropins. Therefore, polyamine participation, especially PUT and SPD, is of importance in the regulation of GnRH and gonadotropin secretion in the neonatal and infantile periods, critical stages in the establishment of sexual differentiation.


Application of Hollow Fibre-Liquid Phase Microextraction Technique for Isolation and Pre-Concentration of Pharmaceuticals in Water.
In this article, a comprehensive review of applications of the hollow fibre-liquid phase microextraction (HF-LPME) for the isolation and pre-concentration of pharmaceuticals in water samples is presented. HF-LPME is simple, affordable, selective, and sensitive with high enrichment factors of up to 27,000-fold reported for pharmaceutical analysis. Both configurations (two- and three-phase extraction systems) of HF-LPME have been applied in the extraction of pharmaceuticals from water, with the three-phase system being more prominent. When compared to most common sample preparation techniques such as solid phase extraction, HF-LPME is a greener analytical chemistry process due to reduced solvent consumption, miniaturization, and the ability to automate. However, the automation comes at an added cost related to instrumental set-up, but a reduced cost is associated with lower reagent consumption as well as shortened overall workload and time. Currently, many researchers are investigating ionic liquids and deep eutectic solvents as environmentally friendly chemicals that could lead to full classification of HF-LPME as a green analytical procedure.


Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats.
A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug seeking after intravenous cocaine self-administration. Male Long-Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug seeking provides further potential for treatment by epigenetic modulation.


Severe hyponatremia during therapy with fluoxetine.
We described two elderly patients with severe hyponatremia that was probably caused by inappropriate secretion of antidiuretic hormone. The hyponatremia arose during fluoxetine (Prozac) antidepressant therapy.


Regulation of the Drosophila protein timeless suggests a mechanism for resetting the circadian clock by light.
Circadian behavioral rhythms in Drosophila depend on the appropriate regulation of at least two genes, period (per) and timeless (tim). Previous studies demonstrated that levels of PER and TIM RNA cycle with the same phase and that the PER and TIM proteins interact directly. Here we show the cyclic expression of TIM protein in adult heads and report that it lags behind peak levels of TIM RNA by several hours. We alsoshow that nuclear expression of TIM depends upon the expression of PER protein. Finally, we report that the expression of TIM, but not PER, is rapidly reduced by light, suggesting that TIM mediates light-induced resetting of the circadian clock. Since both PER and TIM RNA are unaffected by light treatment, the effects of light on TIM appear to be posttranscriptional.


Differential DM20 mRNA expression distinguishes two distinct patterns of spontaneous recovery from murine autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS) mediated by T cells responding to CNS myelin proteins. Immunization of SWXJ mice with the immunodominant p139-151 peptide of myelin proteolipid protein (PLP) results in a relapsing-remitting pattern of EAE characterized by incomplete remyelination during clinical recovery. In the present study we observed two distinct clinical patterns of spontaneous remission during recovery from EAE, viz., sustained remission involving continuous neurologic improvement and aborted remission involving modest transient clinical improvement. We hypothesized that the ability to recover from autoimmune demyelination was directly linked to remyelination events that recapitulated developmental processes. Quantitative immunocytochemistry of CNS tissue showed decreased demyelination in mice undergoing sustained remission compared to mice undergoing aborted remission. Quantitative RT-PCR analysis showed elevated expression of DM20, the developmental isoform of PLP, in CNS tissue from mice undergoing sustained remission compared to mice undergoing aborted recovery. Moreover, DM20 expression was similarly elevated in CNS tissue from mice undergoing sustained recovery from EAE relapse. Our data indicate that expression of the developmental DM20 isoform of PLP is intimately associated with decreased demyelination and sustained clinical recovery from EAE. Thus, DM20 gene expression may provide an appropriate molecular target for promoting CNS remyelination and may serve as a useful marker for predicting clinical outcome and assessing the effectiveness of strategies aimed at promoting CNS tissue repair during autoimmune demyelinating disease.


Heterogeneity of epithelial marker expression in routinely processed, poorly differentiated carcinomas.
The application of immunohistochemical markers against epithelial antigens has proved useful for studying tumor differentiation and in aiding tumor diagnosis. However, the reactivity of various epithelial markers with poorly differentiated carcinomas (the situation in which they are most often used) has not been well established. As a result, it is unclear how negative results should be interpreted and how often more than one antibody may be needed to document the epithelial nature of poorly differentiated neoplasms. We studied 98 poorly differentiated epithelial tumors with AE1, CAM 5.2, and EMA to assess the use of these markers in their diagnosis. Both CAM 5.2 and EMA provided support for epithelial differentiation in 71% (70/98) of the cases, while AE1 stained 50% (49/98) of the tumors; CAM 5.2 was the single most useful marker in the subset of poorly differentiated neuroendocrine carcinomas, staining 20 (77%) of 26 tumors. Use of these markers in pairs increased the recognition of epithelial differentiation (at least one marker showing positive staining) as follows: AE1/CAM 5.2, 80% (78/98); AE1/EMA, 87% (85/98); and CAM 5.2/EMA, 99% (97/98). Thirty carcinomas stained with all three markers, 34 with two markers, and in 34 cases only one antibody supported epithelial differentiation. Twelve (21%) of 58 tumors showed evidence of S100 reactivity. None of the 71 cases to which PD7 was applied showed staining This study indicates that poorly differentiated carcinomas are heterogeneous in their expression of antigens recognized by AE1, CAM 5.2, and EMA. Moreover, these results quantitate the probability of reactivity with poorly differentiated carcinomas for each marker and support the use of one or more antibodies in a "backup" panel when a negative result is obtained with a single antibody and the diagnosis of carcinoma is still suspected.


Neuronal inputs and outputs of aging and longevity.
An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging.


Histopathologic Findings of Coronavirus in Lung: A Mini-Review.
Coronaviruses (CoVs) are important human and animal pathogens. There have been several outbreaks of lung involvement by this category of viruses in the world, ie, severe acute respiratory syndrome (SARS-CoV-1) in 2002 and 2003, the Middle East respiratory syndrome (MERS-CoV) in 2012, and the new coronavirus (2019-nCoV) outbreak of pneumonia from Wuhan, China, since December 2019. There have been several studies about the clinical features and imaging features, but very few reports have been published about pathologic findings in lung tissue, which was partly because of the lack of tissue diagnosis secondary to suddenness of the outbreak. Overall, less than 30 reports have been published in the literature about histologic findings of lung in these viruses, so far. In this report, we will review the published reports about the histopathologic findings of lung tissue in the patients infected with SARS-CoV-2 in comparison with 2 other coronaviruses that have caused outbreaks, ie, SARS-CoV-1 and MERS-CoV.


Census undercount and the undercount of the Black population.
"Despite the [U.S.] Census Bureau's great efforts in various accuracy-improvement and outreach programs, census undercount still persists.... This paper focuses on the undercount of the Black population and its impacts in the form of such biased statistics on Blacks as inflated proportions of Black female-headed households, deflated victimization rates of Black males, or crude death rates of Blacks. The paper concludes with suggestions on how to deal with the undercount problems."


How to avoid complications of distraction osteogenesis for first brachymetatarsia.
Distraction osteogenesis may be used for the treatment of brachymetatarsia. However, few reports have been published on first metatarsal lengthening by this method. We evaluated the complications of distraction osteogenesis for first brachymetatarsia and here we provide a solution. 16 patients (27 feet) underwent distraction osteogenesis for first brachymetatarsia. Mean age at time of surgery was 20 (12-34) years and mean duration of postoperative follow-up was 5 (2-13) years. A unilateral external fixator was fixed at the medial aspect of the metatarsus. The distraction axis was parallel to the plantar surface of the foot in the sagittal plane and to the second metatarsal axis in the transversal plane. First metatarsal length expressed as a proportion of second metatarsal length was 60% (55-64). Average degree of metatarsal lengthening was 42% (34-54), and the average lengthening index was 64 (39-93) days/cm. The most common complication was stiffness of the metatarsophalangeal joint (12 feet). Deformities that included cavus foot and hallux valgus occurred in 3 feet each, and callus fractures occurred in 3 feet. The other complications were pin breakage and pin tract infection in 2 feet each. Distraction osteogenesis for first brachymetatarsia can give satisfactory cosmetic and functional results. However, several complications are commonly encountered. This report on complications and their solutions may help those attempting distraction osteogenesis for first brachymetatarsia.


Beta-adrenergic modulation of pulmonary transvascular fluid and protein exchange.
We determined in anesthetized sheep whether isoproterenol, a beta-adrenergic agonist, prevents the increases in pulmonary fluid and protein exchange produced by thrombin-induced intravascular coagulation. Seven sheep were infused intravenously with 0.05 micrograms X kg-1 X min-1 isoproterenol before infusion of alpha-thrombin, and six sheep were infused with alpha-thrombin only and served as control subjects. The marked increases in pulmonary lymph flow and lymph protein clearance in the control thrombin group were attenuated (P less than 0.05) in the isoproterenol group in association with a higher pulmonary blood flow (P less than 0.05) and a lower pulmonary vascular resistance (P less than 0.05) in the isoproterenol group and with similar increases in pulmonary arterial and pulmonary arterial wedge pressures in both groups. The decreases in fluid and protein fluxes produced by isoproterenol are related to its beta-adrenergic properties because propranolol, a beta-adrenergic antagonist, blocked the protective effects of isoproterenol in a second group of sheep infused with propranolol, isoproterenol, and thrombin. Raising left atrial pressure to test for changes in vascular permeability increased protein flux to a much greater extent in the thrombin control group than in the isoproterenol group challenged with thrombin. The data suggest that isoproterenol attenuated the increase in fluid and protein fluxes produced by thrombin-induced intravascular coagulation by a permeability-decreasing mechanism.


Increased G + C content of DNA stabilizes methyl CpG dinucleotides.
The vertebrate genome is a mosaic of regions differing dramatically in their G + C content. Those regions with a high G + C content contain the expected number of CpG dinucleotides and we propose that following methylation these have been protected from deamination by the increased stability of the surrounding DNA duplex. This argument applies both to the microenvironment of the CpG dinucleotide and to whole gene regions.


Hyrtiosenolides A and B, two new sesquiterpene gamma-methoxybutenolides and a new sterol from a Red Sea sponge Hyrtios species.
Two new sesquiterpene gamma-methoxybutenolides, hyrtiosenolides A (1) and B (2), together with a new 4alpha-methyl polyoxygenated steroid, hyrtiosterol (3), were isolated from a Red Sea sponge, Hyrtios species. Their structures were elucidated by analysis of their 1D and 2D NMR spectra and HRFABMS. Compounds 1 and 2 showed weak antibacterial activity against Escherichia coli.


Rare intraspinal clear cell meningioma in children: a case report and literature review.
Meningioma of the spinal canal is very rare. Clear cell meningioma (CCM) with special histological features occurs more commonly in the spinal cord. A review of the published English-language literature identified 40 reported cases of children with intraspinal CCM and this current report presents an additional case of a 3-year-old child with confirmed lumbar CCM. The current case underwent gross total resection of the CCM. At 9 months after the operation, lumbar magnetic resonance imaging was undertaken and confirmed the absence of tumour recurrence. The child was able to walk normally again. During this period, the child did not receive adjuvant treatments such as radiotherapy and chemotherapy. An evaluation of the 41 cases demonstrated the following: (i) there was no significant difference between the recurrence rate of females and males; (ii) there was a significant difference in the recurrence rate based on the extent of resection (gross total resection versus partial resection); (iii) the recurrence rate in patients where the number of involved segments ≥3 levels was significantly higher than that in patients where the number of involved segments was 1-2 levels. For children with CCM, complete surgical resection might be an important characteristic for predicting the risk of the recurrence of CCM.


[Influence of retention or resection subpatellar fat pad on patella height during rheumatoid knee replacement].
To compare influence of retention or resection subpatellar fat pad on patella height during rheumatoid knee replacement. Totally 48 patients with rheumatoid arthritis who underwent total knee replacement from October 2013 to October 2017 were retrospectively analyzed and divided into resection and retention subpatellar fat pad group. There were 23 patients in resection subpatellar fat pad group, including 9 males and 14 females aged from 48 to 69 years old with an average of(55.83±5.65) years old; subpatellar fat pad were resected during opertaion. There were 25 patients in retention subpatellar fat pad group, including 6 males and 19 femlaes aged from 49 to 70 years old with an average age of (55.52± 6.28) years old;subpatellar fat pad were retentedduring opertaion. Postopertaive complications were observed between two groups, visual analogue scale (VAS) and Hospital for Special Surgery (HSS) at 1 year after operation were used to evaluate relieve pain degree and clnical effect of knee joint, Insall-Salvati ratio(I-S ratio) was used to compare changes of postoperative patella height at 1 year after operation. All patients were followed up from 12 to 39 months with an average of (23.85± 8.82) months. The postoperative wound healed well without infection complications and no prosthetic loosening or revision. Postoperative VAS score at 1 year between two groups was lower than that of before opertaion(P<0.05), but no statistical difference between two groups at 1 year after operation(P>0.05). Postopertaive HSS score between two groups was higer than that of before operation(P<0.05), while no difference in HSS score at 1 year after operation between two groups (P>0.05). I-S ratio of subpatellar fat pad resection group (1.03±0.04) was lower than that of subpatellar fat pad retention group (1.06±0.06), and difference was statistically significant (P<0.05). Resection or retention subpatellar fat pad in rheumatoid knee replacement have advantages of relieving postoperative pain and improving functional recovery, however, retention of infrapatellar fat pad is beneficial to restoration of patellar height.


Diabetes Status is Associated With Plantar Soft Tissue Stiffness Measured Using Ultrasound Reverberant Shear Wave Elastography Approach.
The purpose of this study was to investigate the association between the mechanical properties of plantar soft tissue and diabetes status. 51 (M/F: 21/30) participants with prediabetes onset (fasting blood sugar [FBS] level > 100 mg/dL), age >18 years, and no lower limb amputation were recruited after ethical approval was granted from Pontificia Universidad Catolica del Peru ethical review board. Ultrasound reverberant shear wave elastography was used to assess the soft tissue stiffness at the 1st metatarsal head (MTH), 3rd MTH, and the heel at both feet. Spearman's rank-order correlation (rho) test indicated a significant (P < .05) positive correlations between FBS level and the plantar soft tissue shear wave speed at the 1st MTH: rho = 0.402 (@400 Hz), rho = 0.373 (@450 Hz), rho = 0.474 (@500 Hz), rho= 0.395 (@550 Hz), and rho = 0.326 (@600 Hz) in the left foot and rho = 0.364 (@450 Hz) in the right foot. Mann-Whitney U test indicated a significantly (P < .05) higher shear wave speed in the plantar soft tissue with the following effect sizes (r) at the 1st MTH of the left foot at all tested frequencies: r = 0.297 (@450 Hz), r = 0.345 (@500 Hz), r = 0.322 (@550 Hz), and r = 0.275 (@600 Hz), and at the 1st MTH of right foot r = 0.286 (@400 Hz) in diabetes as compared with the age and body mass index matched prediabetes group. An association between fasting blood sugar level and the stiffness of the plantar soft tissue with higher values of shear wave speed in diabetes versus prediabetes group was observed. This indicated that the proposed approach can improve the assessment of the severity of diabetic foot complications with potential implications in patient stratification.


Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment.
The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force.


Nanoporous selenium as a cathode material for rechargeable lithium-selenium batteries.
Nanoporous selenium was prepared by a simple mechanical method adopting nano-CaCO3 as a template. When used as a cathode, it can exhibit relatively high capacity and good cycling behaviour. These results present great promise for this new cathode material for rechargeable lithium batteries of high energy density.


Genome beginnings: rooting the tree of life.
A rooted tree of life provides a framework to answer central questions about the evolution of life. Here we review progress on rooting the tree of life and introduce a new root of life obtained through the analysis of indels, insertions and deletions, found within paralogous gene sets. Through the analysis of indels in eight paralogous gene sets, the root is localized to the branch between the clade consisting of the Actinobacteria and the double-membrane (Gram-negative) prokaryotes and one consisting of the archaebacteria and the firmicutes. This root provides a new perspective on the habitats of early life, including the evolution of methanogenesis, membranes and hyperthermophily, and the speciation of major prokaryotic taxa. Our analyses exclude methanogenesis as a primitive metabolism, in contrast to previous findings. They parsimoniously imply that the ether archaebacterial lipids are not primitive and that the cenancestral prokaryotic population consisted of organisms enclosed by a single, ester-linked lipid membrane, covered by a peptidoglycan layer. These results explain the similarities previously noted by others between the lipid synthesis pathways in eubacteria and archaebacteria. The new root also implies that the last common ancestor was not hyperthermophilic, although moderate thermophily cannot be excluded.


Caffeine alters A2A adenosine receptors and their function in human platelets.
Caffeine acts mainly via blockade of adenosine receptors, which have been classified into A1, A2A, A2B, and A3 subtypes. We determined whether repeated caffeine administration (750 mg/d for 1 week) upregulates the human platelet A2A adenosine receptor and is accompanied by sensitization of platelet responses (increase in cAMP accumulation and decrease in platelet aggregation) to selective stimulation of the A2A receptors. Platelets were obtained from peripheral venous blood of 9 human volunteers at the end of 1 week of caffeine abstinence (control) and at 12 and 60 hours after the last dose of caffeine (withdrawal). The A2A receptor radioligand [3H]SCH 58261 (5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]-pyrimidine) bound to a single affinity class of sites in platelet membranes from controls with a Bmax of 98+/-2 fmol/mg protein and a KD of 1.29+/-0.05 nmol/L. At 12 and 60 hours after caffeine withdrawal, the radioligand bound with similar affinity (KD=1.36+/-0.06 and 1.21+/-0.05 nmol/L, respectively), but the Bmax was increased (P<0.01) to 128+/-3 and 132+/-2 fmol/mg protein. The A2A receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA) increased cAMP accumulation (EC50=59+/-3 nmol/L) and inhibited (IC50=90+/-6 nmol/L) aggregation of control platelets. The EC50 values for HE-NECA to increase cAMP accumulation of platelets were reduced (P<0.01) at 12 and 60 hours after caffeine withdrawal (31+/-3 and 21+/-2 nmol/L, respectively). The IC50 values for HE-NECA to inhibit ADP-induced platelet aggregation were 50+/-5 and 30+/-2 nmol/L at 12 and 60 hours after caffeine withdrawal, respectively. Chronic caffeine intake leads to upregulation of A2A receptors and is accompanied by sensitization to the actions of the agonist HE-NECA.


Charge modification of plasma and milk proteins results in antiviral active compounds.
Previous studies have shown that acylated plasma and milk proteins with increased negative charge, derived from various animal and human sources, are potent anti-HIV compounds. The antiviral effects seemed to correlate positively with the number of negative charges introduced into the various polypeptides: proteins with a high content of basic amino acids in which all of the available epsilonNH2 groups were anionized yielded the most potent anti-HIV compounds. It remained unclear however whether the total net negative charge of the various derivatized proteins, or rather the charge density on the protein backbone, is essential for the observed anti-HIV activity. Earlier studies have shown that acylated albumins preferentially block the process of HIV/cell fusion through binding to the HIV envelope proteins gp120 and gp41 as well as to the cell surface of the HIV target cells. Some of these polyanionic proteins have been shown to interfere also with the gp120-CD4 mediated virus/cell binding. The relative contribution of these effects to the anti-HIV activity may depend both on the total negative charge introduced as well as the hydrophobicity of the acylating reagent added to the particular proteins. In this study we show that the higher the charge density of the derivatized proteins, the more potent their HIV replication inhibiting effects are. In contrast, the addition of positive charge to the studied plasma and milk proteins through amination resulted in a reduced anti-HIV activity but a clearly increased anti-HCMV activity, with IC50 values in the low micromolar concentration range. Interestingly, native lactoferrin (Lf) was antivirally active against both HIV and HCMV. Acylation or amination of Lf increased the anti-HIV and anti-HCMV activity, respectively. The N-terminal portion of Lf appeared essential for its anti-HCMV effect: N-terminal deletion variants of human Lf were less active against HCMV. Circular dichroism of the modified proteins showed that the secondary structure of the tested proteins was only moderately influenced by acylation and/or covalent attachment of drugs, making these (derivatized) proteins useful candidates as antiviral agents and/or intrinsically active drug carriers. The relatively simple chemical derivatization as well as the abundant sources of blood plasma and milk proteins provides attractive opportunities for the preparation of potent and relatively cheap antiviral agents for systemic or local applications.


[Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction].
Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.


Photo-induced interaction of antibacterial quinolones with human serum albumin.
The absorption and fluorescence spectrums of four antibacterial quinolones, namely, ciprofloxacin, norfloxacin, enoxacin, and cinoxacin, were studied in the presence of human serum albumin (HSA). Of the three fluoroquinolones studied, ciprofloxacin and norfloxacin were found to bind efficiently to HSA when irradiated with visible light, whereas the third, enoxacin, bound only moderately. On the other hand, cinoxacin, a nonfluorinated quinolone of the first generation, did not show any interaction with HSA. The findings were inferred by monitoring the evolution of the fluorescence spectrums of the solutions as a function of time. A direct relationship between the capacity of the photo-induced defluorination to produce aryl cation intermediates, and the subsequent binding reaction with HSA, was observed and is discussed.


Engineering multifunctional protein nanoparticles by in vitro disassembling and reassembling of heterologous building blocks.
The engineering of protein self-assembling at the nanoscale allows the generation of functional and biocompatible materials, which can be produced by easy biological fabrication. The combination of cationic and histidine-rich stretches in fusion proteins promotes oligomerization as stable protein-only regular nanoparticles that are composed by a moderate number of building blocks. Among other applications, these materials are highly appealing as tools in targeted drug delivery once empowered with peptidic ligands of cell surface receptors. In this context, we have dissected here this simple technological platform regarding the controlled disassembling and reassembling of the composing building blocks. By applying high salt and imidazole in combination, nanoparticles are disassembled in a process that is fully reversible upon removal of the disrupting agents. By taking this approach, we accomplish here the in vitro generation of hybrid nanoparticles formed by heterologous building blocks. This fact demonstrates the capability to generate multifunctional and/or multiparatopic or multispecific materials usable in nanomedical applications.


Abdominal Panniculectomy: An Analysis of Outcomes in 238 Consecutive Patients over 10 Years.
Panniculectomy is a commonly performed body contouring procedure to address skin laxity and its related complications. This study aimed to assess clinical outcomes of abdominal panniculectomy and identify predictors of complications at a tertiary academic healthcare center. A retrospective review of patients who underwent panniculectomy between January 2010 and January 2020 at our institution was performed. Exclusion criteria were a history of prior panniculectomy or abdominoplasty. Patient characteristics and clinical outcomes were collected. Univariate and multivariable analyses were performed to assess the risk factors of complications. The mean age in the included 238 patients was 51.7 ± 12.7 years, and the mean body mass index (BMI) at the time of panniculectomy was 33 ± 7.5 kg/m2. Median resection weight was 2.7 kg (range: 0.15-14.6) and median length of hospital stay was 2 days (range: 0-24). Mean follow-up time was 50 ± 37 months. The rate of major complications was 22.3%. Revision surgery was performed in 3.4% of the cases. Multivariable analyses demonstrated that increase in BMI (P = 0.007) and active smoking (P = 0.026) were significantly associated with increased odds of major complication, and increase in BMI (P = 0.0004), history of venous thromboembolism (P = 0.034) and having a concomitant ventral hernia repair (P = 0.0044) were significantly associated with having a length of hospital stay of 3 days or more. Panniculectomy is generally safe to perform, with major postoperative complication rate of 22.3% in our series. Increase in BMI and active smoking were significantly associated with having a major complication. Higher BMI, concomitant hernia repair, and a history of venous thromboembolism were associated with length of hospital stay of 3 days or more.


Biosynthesis of sulfoquinovosyldiacylglycerol in higher plants : use of adenosine-5'-phosphosulfate and adenosine-3'-phosphate 5'-phosphosulfate as precursors.
Adenosine-5'-phosphosulfate (APS) and adenosine-3'-phosphate 5'-phosphosulfate (PAPS) have been used as precursors of sulfoquinovosyldiacylglycerol (SQDG) in intact chloroplasts incubated in the dark. Competition studies demonstrated APS was preferred over PAPS and SO(4) (2-). Rates of SQDG synthesis up to 3 nanomoles per milligram of chlorophyll per hour were observed when [(35)S]APS and appropriate cofactors were supplied to chloroplasts incubated in the dark. The pH optimum for utilization of APS was 7.0. The incorporation was linear for at least 30 minutes. ATP and UTP stimulated the incorporation of sulfur from APS into SQDG, but the most stimulatory additions were DHAP and glycerol-3-P. The concentration curve for APS showed a maximum at 20 micromolar in the absence of DHAP and 30 micromolar in the presence of DHAP. The optimum concentration of DHAP for conversion of APS into SQDG was 2 millimolar. Rates of synthesis up to 4 nanomoles per milligram of chlorophyll per hour were observed when [(35)S]PAPS was the sulfur donor and appropriate cofactors were supplied to chloroplasts. Optimal rates for conversion of sulfur from PAPS into SQDG occurred with concentrations of DHAP between 5 and 10 millimolar. DHAP was by far the most effective cofactor, although ATP and UTP also stimulated the utilization of PAPS for SQDG biosynthesis. In general, triose phosphates, including glycerol-3-P were not effective cofactors for SQDG biosynthesis.


Spinal Epidural Venous Plexus Enlargement as a Cause of Neurologic Symptoms: Vascular Anatomy and MRI Findings.
Pathology of the spinal venous system, unlike that of the spinal arterial system, is rarely considered as a possible cause of clinical symptoms. As the imaging features of the spinal venous anatomy and its diseases are not well-known, related pathologies may be overlooked or misdiagnosed. The major noninvasive technique enabling optimal visualization of spinal venous plexuses is magnetic resonance imaging (MRI). We report MRI findings from three cases of spinal venous plexus engorgement of different etiologies that resulted in neurologic symptoms, including radiculopathy and/or back pain. These cases are discussed in the context of the relevant anatomic and pathophysiologic background.


Parenting Strategies and Adolescents' Cyberbullying Behaviors: Evidence from a Preregistered Study of Parent-Child Dyads.
Little is known about how parents may protect against cyberbullying, a growing problem-behavior among youth. Guided by self-determination theory, a theory concerned with effectively motivating and regulating behavior, six preregistered hypotheses concerning parenting strategies of regulating cyberbullying behavior were tested in 1004 parent-child dyads (45.9% female adolescents; adolescents were either 14 (49.5%) or 15 (50.5%) years old). The results largely supported hypotheses: Parents who used more autonomy-supportive strategies-understanding the adolescent's perspective, offering choice, and giving rationales for prohibitions-had adolescents who reported engaging in less cyberbullying than parents who used controlling strategies (especially using guilt, shame, and conditional regard). Further, this was mediated by lower feelings of reactance to, or a desire to do the opposite of, parents' requests. The discussion focuses on the limits of this study to investigate reciprocal effects of adolescent behavior shaping parenting strategies-a critical agenda for future research-as well as the potential benefits of interventions aimed at increasing parental autonomy support for reducing cyberbullying and other problem behaviors in adolescents.


Magnetic semiconductor: structural, magnetic, and conducting properties of the salts of the 6-oxoverdazyl radical cation with M(dmit)(2) anions (M = Ni, Zn, Pd, and Pt, dmit = 1,3-dithiol-2-thione-4,5-dithiolate).
Five kinds of (1:1), (1:3), and (2:1) salts of 3-[4-(diethylmethylammonio)phenyl]-1,5-diphenyl-6-oxoverdazyl radical cation [V](+) with M(dmit)(2) anions (M = Ni, Zn, Pd, and Pt, dmit = 1,3-dithiol-2-thione-4,5-dithiolate) ([V](+)[Ni(dmit)(2)](-) (1), [V](+)[Ni(dmit)(2)](3)(-) (2), [V](+)(2)[Zn(dmit)(2)](2-) (3), [V](+)(2)[Pd(dmit)(2)](2-) (4), and [V](+)(2)[Pt(dmit)(2)](2-) (5)) and an iodide salt of [V](+) ([V](+)[I](-) (6)) have been prepared, and the magnetic susceptibilities (chi(M) values) have been measured between 1.8 and 300 K. The chi(M) of the (1:1) Ni salt (1) can be well reproduced by the sum of the contributions from (i) a Curie-Weiss system with a Curie constant (C) of 0.376 K emu/mol and a negative Weiss constant (theta) of -1.5 K and (ii) the one-dimensional Heisenberg antiferromagnetic alternating chain system with 2J(A-B)/k(B) = -274 K (alternation parameter alpha = J(A-C)/J(A-B) = 0.2). The chi(M) of the (1:3) Ni salt (2) can be well explained by the two-term contributions from (i) the Curie-Weiss system with C = 0.376 K emu/mol and theta = -5.0 K and (ii) the dimer system with 2J/k(B) = -258 K. The magnetic properties of 1 and 2 were discussed based on the results obtained by crystal structure analysis and ESR measurements of 1 and 2. The chi(M) values of the (2:1) Zn, Pd, Pt salts 3, 4, and 5 and [V](+)[I](-) salt 6 follow the Curie-Weiss law with C = 0.723, 0.713, 0.712, and 0.342 K emu/mol and theta = -2.8, -3.1, -2.6, and +0.02 K, respectively, indicating that only the spins of the verdazyl radical cation contribute to the magnetic property of these salts. The salts 1, 3, and 5 are insulators. On the other hand, the conductivity (sigma) of the Ni salt 2 and Pd salt 4 at 20 degrees C was sigma = 8.9 x 10(-2) and 1.3 x 10(-4) S cm(-)(1) with an activation energy E(A) = 0.11 and 0.40 eV, respectively. The salts 2 and 4 are new molecular magnetic semiconductors.


Fast segmentation and modeling of hepatic components for the planning of robot-assisted liver tumor ablation.
Segmentation and modeling of hepatic components from pre-operative images is very important for treatment planning and guidance in robot-assisted liver tumor ablation. An in-house developed system for hepatic component segmentation and modeling using CT data is presented in this paper. This system includes gross liver segmentation by a 3D mesh deformation model, liver vasculature segmentation by a vessel context-based voting and grouping method, liver tumor segmentation by a support vector machine framework, and other segmentation/modeling tool. This system was tested using 20 data sets from human patients and 5 sets of porcine CT scan. It is suggested by experimental results that the developed system is able to conduct fast segmentation and modeling of hepatic components for both human and large animal, with a satisfying accuracy, to support treatment planning.


Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.
Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group. The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period. BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.


The double-entry intraclass correlation as an index of profile similarity: meaning, limitations, and alternatives.
As applied to many psychological phenomena, analysis of profile similarity has an intuitive appeal that masks complex statistical issues. Psychologists have long debated the methods of indexing similarity between 2 psychological profiles, but the double-entry intraclass correlation may be emerging as a preferred approach. Unfortunately, the double-entry intraclass correlation has not been articulated clearly in terms of fundamental facets of profiles--elevation, scatter, and shape--which prevents full understanding of its meaning. In this article, I (a) articulate these effects, (b) discuss potential limitations and confusions arising from these effects, (c) present a failure to replicate previous empirical findings regarding the double-entry intraclass correlation, and (d) present alternative recommendations for analysis of profile similarity. The conceptual, mathematical, and empirical points may enhance the insights emerging from analyses of profiles and profile similarity.


Multi-component adjustable intraocular lenses: a new concept in pediatric cataract surgery.
The multi-component intraocular lens (IOL) (IVO; SAS, Strasbourg, France) is a novel approach to the treatment of pediatric cataract. Because the refractive requirements for pediatric eyes often change over time, current IOL technology does not easily allow refractive adjustments after the primary surgical intervention. The multi-component IOL concept allows easy, surgical refractive adjustments to the initial surgical implantation at any postoperative time period. Thus, both surgical implantation and enhancement surgery have been successfully accomplished in adult patients. A novel surgical approach to pediatric cataract surgery is described. At the time of the primary surgery, a two component IOL was implanted. At any postoperative time period, the front lens component, located in front of the capsular bag, could be easily surgically exchanged because the dioptric power requirements of the pediatric eye changed over time. Both primary and enhancement surgeries have been done in adult patients with good results. Implantations have occurred uneventfully in all cases with no intraoperative or postoperative complications. There was no statistically significant difference in the endothelial cell density, anterior chamber depth, and pachymetry readings preoperatively and 2 years postoperatively. There was no interlenticular fibrosis present. The multi-component IOL should provide a unique and greatly needed surgically adjustable approach to the treatment of pediatric cataract.


Expression, purification, and characterization of rat aromatic L-amino acid decarboxylase in Escherichia coli.
A cDNA encoding rat aromatic L-amino acid decarboxylase (AADC) was successfully expressed in Escherichia coli using a T7 RNA polymerase expression system. Two types of expression vectors were tested and revealed to be equivalent to produce AADC. The enzyme was purified in both cases. The ratio of recovery of the pure active recombinant protein was better when the purification of the protein was made easier by addition of a short His-Tag at the C-terminal moiety of AADC, as achieved in the case of pET-20b+ vector expression. Spectral characteristics of the bound pyridoxal-5'-phosphate were essentially identical to the spectral properties of rat AADC. Kinetic constants Km and Vmax of recombinant AADC for the natural substrates L-dihydroxyphenylalanine and 5-hydroxytryptamine were 0.14 mM and 8444 U/mg, and 0.066 mM and 1813 U/mg, respectively. These values were in good agreement with previously reported values for AADC of the rat and other mammalian species.


An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids.
Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary alpha-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary alpha-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (beta-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle physiological responses on mammalian metabolism, and can be employed to investigate the potential adverse effects of other nanoparticles and nanomaterials on the environment and human health.


No evidence for a large difference in ALS frequency in populations of African and European origin: a population based study in inner city London.
Abstract Previous studies have suggested a lower incidence of ALS in people of African origin. We used a population based register in an urban setting from inner city London postcodes where there is a large population of people of African ancestry to compare the frequency of ALS in people of European and African origin. Population statistics stratified by age, gender and ethnicity were obtained from the 2001 census. Incidence and prevalence were calculated in each ethnic group. Results showed that in a population of 683,194, of which 22% were of African ancestry, 88 individuals with ALS were identified over a seven-year period, including 14 people with African ancestry. The adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3) and in those of European ancestry 1.97 per 100,000 person-years (95% CI 1.55-2.48). In conclusion, in this small population based study we could not detect a difference in rates of ALS between people of African ancestry and those of European ancestry.


18 F-Fluorodeoxyglucose triple-headed coincidence detection imaging in oncology: preliminary results and comparison with dedicated PET.
Dual head coincidence (DHC) imaging has been proposed as a valuable and cheaper alternative to oncological PET. The increased sensitivity of the recently-developed triple-headed gamma camera (THC) optimized for coincidence detection has not been either validated or compared to the sensitivity of a dedicated PET system in a clinical study. Differences in contrast-to-noise-ratio (CNR) between dedicated FDG PET, DHC and THC imaging were assessed using a hot sphere phantom. Twenty-two oncological patients were prospectively studied with consecutive whole body FDG PET and FDG THC imaging. The images were visually read by 2 experienced nuclear medicine specialists. The diagnostic sensitivity of FDG THC imaging was assessed using FDG PET as the imaging gold standard. Lesion size was determined using computed tomography or magnetic resonance imaging. The mean gain in CNR for THC as compared to DHC imaging was 35% (10-56%). Of 63 lesions, 58 (92%) on FDG PET were also detected with THC imaging. Considering only lesions smaller than 15 mm, the relative sensitivity was 86% (24/29). All lesions above 15 mm (n=34) were detected using THC imaging. The first clinical results for THC imaging are promising. The overall relative sensitivity in this limited series was 92%. Only a few lesions smaller than 15 mm were missed.