Implications of dose rounding of chemotherapy to the nearest vial size.
There are practical implications of preparing cytotoxic doses calculated to the exact milligram. The objective here was to explore the magnitude of the effect of dose rounding to the nearest whole vial strength for some newly marketed expensive cytotoxic chemotherapy agents. Body surface areas (BSA) of 2838 adult patients presenting for chemotherapy at the Peter MacCallum Cancer Centre between May 1996 and December 2000 were calculated by using the DuBois and DuBois linear equation to two decimal places. Each individual dose of docetaxel, liposomal doxorubicin, gemcitabine, oxaliplatin and vinorelbine was calculated from the actual BSA based on the dose recommended in the approved drug product information. This calculated dose was then rounded upwards to the full next vial if the calculated dose exceeded above 50% of the next appropriate vial strength and was rounded downwards to the full previous vial if the calculated dose did not exceed above 50% of the next appropriate vial strength. Potential impacts on cost were calculated in Australian dollars for each drug for both the calculated and rounded dose on those instances where the difference was no greater than +/-5%. The proportion of patients in whom the dose rounded to the nearest vial strength varied by not more than +/-5% was 89.5% for docetaxel, 60.4% for liposomal doxorubicin, 99.4% for gemcitabine, 34% for oxaliplatin and 56.3% for vinorelbine. The implications of dose rounding in financial terms are significant and project savings of 4-14.2%. The judicious application of dose rounding of chemotherapy agents is possible without any negative clinical effect. It is feasible to dose round to the nearest vial for those cytotoxic agents that are available in multiple vial sizes.


Poison hemlock determination in postmortem samples.
Poison hemlock (Conium maculatum L.) is a weed that grows rampant in many areas of North America. Forensic toxicology laboratories rarely receive requests to analyze biological specimens for the presence of poison hemlock. This report discusses two postmortem cases that were encountered over a decade apart and describes different analytical approaches that may be used to quantify coniine, a primary poison hemlock alkaloid, in biological specimens. The first case is from 2004 and involves a 27-year-old female that was found deceased in a relatively isolated area of California. Based on the presence of plant material at the scene and signs of its ingestion at autopsy, the possibility of hemlock poisoning was considered. Toxicological testing of the blood and gastric content by quantitative selected-ion monitoring Gas Chromatography/Mass Spectrometry (SIM-GC/MS) revealed the presence of coniine at concentrations of 410 ng/mL and 9300 ng/mL, respectively. The second case is from Pennsylvania and was sent for analysis in the spring of 2019. In this case, a male in his forties was found deceased in the kitchen area of a camper. Green substances, in liquid and residue forms, were observed in the sink. Mixtures of leaf-like material were also found in several bowls and pans. Subclavian blood screened positive for coniine by full-scan Gas Chromatography/Mass Spectrometry (GC/MS). Semi-quantitative confirmation testing was performed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and showed the presence of coniine at a concentration of 35 ng/mL. These analytical approaches can be used to substantiate or exclude poison hemlock exposure as a cause of death.


Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.
The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.


Hepatic cyst with intracystic bleeding: contrast-enhanced sonographic findings.
Intracystic bleeding is a relatively rare complication of hepatic cysts, which is very difficult to diagnose by conventional sonography (US). Hence, a new US technique has been sought for this purpose. We present the case of a hepatic cyst with intracystic bleeding in which contrast-enhanced US showed microbubbles oozing from the cyst wall into the cystic cavity. Contrast-enhanced US is now an important diagnostic tool for diagnosing liver tumors, but contrast-enhanced US findings relating to intracystic bleeding have not been reported. Our observations suggest that this technique may be a useful new diagnostic tool for this purpose.


[Amalgam. XI. Glass-ionomer as a possible substitute of amalgam: longevity].
The clinical use of glass-ionomer increases, also for restorative goals. The longevity of glass ionomer restorations is among others determined by premature contact with saliva and by acid erosion. The adherence to the dental hard tissues may be increased by acid pretreatment. The longevity data presented here indicate that glass ionomer restorations do not last as long as amalgam restorations. In the deciduous teeth the material seems to be a more acceptable substitute for amalgam. The same holds true for restorations which are not submitted to stress, such as class V.


Development of real-time PCR (TaqMan) assays for the detection and quantification of Botrytis cinerea in planta.
Real-time PCR assays based on TaqMan chemistry have been developed for the detection and quantification of Botrytis cinerea, suitable for a wide range of different host plant species. Assays were designed to the beta-tubulin gene, the intergenic spacer (IGS) region of the nuclear ribosomal DNA and also to a previously published, species-specific sequence characterised amplified region (SCAR) marker; the assays were compared to a published method based on SYBR Green I technology. The assays designed to the IGS region and SCAR marker proved to be highly specific for B. cinerea but assays designed to the beta-tubulin gene and the previously published assay designed to the cutinase-A gene both cross-react with B. fabae. The assay designed to the IGS region was the most sensitive and was able to reliably detect and quantify as little as 20 fg of B. cinerea DNA. The method incorporates the detection of a gene from the plant host to compensate for variations in extraction efficiency and size of sample tested. The assays designed were used to follow the progression of infection of B. cinerea in plant material inoculated with spores to the point of symptom induction. They should be ideally suited to investigating infection processes in-planta and could be used to investigate aspects of infection/plant pathogenesis, by B. cinerea and are particularly suited to the detection and quantification of the pathogen prior to the development of symptoms.


Juvenile Dermatomyositis: what comes next? Long-term outcomes in childhood myositis from a patient perspective.
To describe long-term outcomes in JDM using patient questionnaires and link to longitudinal, prospectively collected data for each patient within the Juvenile Dermatomyositis Cohort and Biomarker Study, UK and Ireland (JDCBS) to determine outcome predictors. METHODS: JDCBS participants aged ≥ 16y completed the SF36, HAQ and a questionnaire regarding current disease features, medications, education and employment. Data collected from the JDCBS included disease subtype, demographics, clinical and laboratory features. Intensity indices were calculated for physician VAS, modified skin DAS, CMAS and MMT8 by dividing area under the curve (AUC) from longitudinal score trajectories by duration of study follow-up (y). Relationships between questionnaire and JDCBS clinical / laboratory data were investigated fitting statistical models appropriate for cross sectional and longitudinal data. Of 190 questionnaires sent, 84 (44%) were returned. Average age of respondents was 20.6 years (SD 3.9), time since diagnosis was 12.4 years (SD 5.0), age at onset was 9.2 years (SD 4.3), female to male ratio 4.25:1. Forty-nine (59%) self-reported persistently active disease, 54 (65%) were still taking immunosuppressive medication. 14/32 at school/higher education reported myositis adversely affecting academic results. 18-24 year-olds were twice as likely to be unemployed compared the UK population (OR = 0.456, 95% CI 0.24, 0.84, p = 0.001). Participants ≥ 18 years were three times as likely to be living with a parent/guardian (OR = 3.39, p < 0.001). SF36 MCS and MMT8 intensity index scores were significantly correlated (ρ = 0.328, p = 0.007). After 12.4 years, questionnaire responders reported self-perceived high rates of persistently active disease and medication use, reduced rates of employment and were more likely to live with a parent/guardian. Perceived persistently active muscle disease appeared to affect quality of life in these patients and was the most significant contributor to long-term outcomes. Our findings highlight the importance of including the patient perspective in the assessment of long term outcomes, so that that we can start to target initial management strategies more effectively based on a combination of clinical and patient-reported data.


Phylogenetics of the Monogenea--evidence from a medley of molecules.
Nuclear ribosomal DNA sequences of Monogenea from both complete small and partial large (D1-D2) subunits were determined and added to previously published sequences in order to best estimate the molecular phylogeny of the group. A total of 35 ssrDNA, 100 D1 lsrDNA and 51 D2 lsrDNA monogenean sequences were used, representing a total of 27 families. From these sequences different data sets were assembled and analysed to make the best use of all available molecular phylogenetic information from the taxa. Maximum parsimony and minimum evolution trees for each data partition were rooted against published sequences from the Cestoda, forcing the Monogenea to appear monophyletic. There was broad agreement between tree topologies estimated by both methods and between genes. Well-supported nodes were restricted to deeply diverging major groupings and more derived taxa with the lsrDNA data but were at most nodes with ssrDNA. The Polyonchoinea showed the greatest resolution with a general pattern of ((Monocotylidae(Capsalidae(Udonellidae+Gyrodactylidea)))((Anoplodiscidae+Sundanonchidae)(Pseudomurraytrematidae+Dactylogyridae))). The Heteronchoinea readily split into the Polystomatoinea+Oligonchoinea, and Chimaericolidae and Hexabothriidae were successively the most basal of oligonchoinean taxa. Relationships within the Mazocraeidea, comprising 27 families of which 15 were sampled here, were largely unresolved and appear to reflect a rapid radiation of this group that is reflected in very short internal branches for ssrDNA and D1 lsrDNA, and highly divergent D2 lsrDNA. A reduced morphological matrix, employing only those families represented by molecules, contrasted sharply with respect to polyonchoinean interrelationships. Deep branches of the Heteronchoinea were similar for both classes of data but also showed that the interrelationships of the mazocraeidean families are labile and susceptible to sampling.


A test battery to assess intrasensory and intersensory development of young children.
The purpose of the study was to develop a battery of tests for use in evaluation of intra- and intersensory development of young children. A battery of 15 tests (4 visual, 4 auditory, 4 tactile-kinesthetic, and 3 intersensory) was administered to 109 normally developing 6- and 8-year-old and 32 slowly developing or learning disabled children. Interdependence of test items within each intrasensory and the intersensory category was determined; intercorrelations ranged from .00 to .78. Reliability estimates were also determined. Face validity was claimed for each item. The effects of age or developmental level on test performance were established. Based upon the interdependence of the tests, reliability estimates, and the capacity of the tests to discriminate among groups classified according to age or developmental level, a battery of 10 intra- and intersensory tests was proposed. The battery has 3 tests of visual perception-visual memory, dynamic depth perception, and size discrimination; 3 tests of auditory perception-auditory discrimination, auditory memory of related syllables, and auditory sequential memory of numbers; 2 tests of tactile-kinesthetic perception-tactile integration and movement awareness; and 2 tests of intersensory integration-auditory-tactile intergration and auditory-visual integration.


Neuregulin-1β Plays a Neuroprotective Role by Inhibiting the Cdk5 Signaling Pathway after Cerebral Ischemia-Reperfusion Injury in Rats.
This study investigated the effects of neuregulin-1β (NRG1β) after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats to evaluate whether they occur via the cyclin-dependent kinase (Cdk)5 signaling pathway. One hundred adult male Wistar rats were randomly divided into sham, MCAO/R, treatment (NRG1β), inhibitor (roscovitine; Ros), and inhibitor + treatment (Ros + NRG1β) groups. The MCAO/R model was established using the intraluminal thread method. The neurobehavioral function was evaluated by the modified neurological severity score (mNSS). The cerebral infarction volume (CIV) was measured by triphenyl tetrazolium chloride (TTC) staining. Morphological changes were observed by hematoxylin-eosin (HE) staining. The apoptotic cell index (ACI) was detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Immunohistochemistry and Western blotting were performed to detect the expression of calpain 1, p35/p25 (regulatory binding partners of Cdk5), Cdk5, and p-Tau in neurons. The neuronal morphology in the MCAO/R, NRG1β, Ros + NRG1β, and Ros groups differed compared to the sham group; the mNSS, CIV, ACI, and the expression of calpain 1, p35/p25, Cdk5, and p-Tau were significantly increased in all four groups (P < 0.05). In the NRG1β, Ros and Ros + NRG1β groups, the neuronal morphology was significantly improved compared to the MCAO/R group, as were the mNSS, CIV, and ACI. The levels of calpain 1, p35/p25, and p-Tau were decreased compared with the MCAO/R group (P < 0.05), while the Cdk5 expression was not significantly different (P > 0.05). NRG1β may exert neuroprotective effects by inhibiting the expression of calpain 1, p35/p25, and p-Tau after cerebral ischemia-reperfusion injury.


Cephalometric characteristics of Class II division 1 malocclusion in a Saudi population living in the western region.
To describe and analyze the cephalometric dento-skeletal characteristics associated with Angle's Class II, division 1 malocclusion in Saudi population living in the western region. The material examined included 149 lateral head radiographs comprising two series: (1) 85 films of children with Class II, division 1 malocclusion and (2) 62 films of children with "normal" occlusion. Age range of the representing children was 10-13 years. In Class II division 1 subjects, the maxilla was prognathic in relation to anterior cranial base. The mandible was normally positioned in relation to anterior cranial base. Upper incisors were proclined and lower incisors were normally positioned. The cranial base angle was not different between the two groups. In the western region of Saudi Arabia, Class II division 1 malocclusion has specific characteristics. The presence of prognathic maxilla, in this sample, indicates that the use of head gear therapy might be more appropriate than functional appliances when treating Class II division 1 malocclusion in Saudis living in the Western region.


Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation.
Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5'-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism.


Global anti-synchronization of a class of chaotic memristive neural networks with time-varying delays.
This paper is concerned with the global exponential anti-synchronization of a class of chaotic memristive neural networks with time-varying delays. The dynamic analysis here employs results from the theory of differential equations with discontinuous right-hand side as introduced by Filippov. And by using differential inclusions theory, the Lyapunov functional method and the inequality technique, some new sufficient conditions ensuring exponential anti-synchronization of two chaotic delayed memristive neural networks are derived. The new proposed results here are very easy to verify and they also improve the earlier publications. Finally, a numerical example is given to illustrate the effectiveness of the new scheme.


68Ga DOTANOC PET/CT for accurate delineation of disease extent in a case of sinonasal small cell neuroendocrine carcinoma.
Neuroendocrine tumors constitute a heterogeneous group of neoplasms arising from the cells of the neural crest. We present a rare case of primary sinonasal neuroendocrine carcinoma in a 61-year-old male patient where somatostatin receptor PET/CT with 68Ga-DOTANOC correctly delineated the extent of primary tumor as compared to contrast-enhanced CT, thereby changing patient management.


[Chronic granulomatous endophthalmitis. Clinical-pathological correlation].
The authors present the case of a patient with a painful eye secondary to a non-perforating traumatism sustained in the past which, at the time of the injury, had caused a post-traumatic cataract, corneal lesions and a secondary glaucoma. The structural damage of the ocular content, associated with a well preserved size and external shape, made the diagnosis more difficult, requiring additional diagnostic methods. The pathological findings are also presented. The authors present the available diagnostic methods for those cases with chronic inflammation in which direct examination of the ocular content is not feasible, and it is mandatory to exclude vital threatening pathologies.


Decatungstate photocatalyzed oxidation of aryl alkanols. Electron transfer or hydrogen abstraction mechanism?
[reaction: see text] Decatungstate W(10)O(32)(4-) photosensitized oxidation of a series of para-X-substituted 1-aryl-1-alkanols was investigated. The only oxidation product of the side-chain of the 1-aryl-1-alkanol was the aryl ketone. The product analysis and kinetic data of the title reaction support a hydrogen atom transfer mechanism in the rate-determining step.


Prognostic factors of tracheobronchial mucoepidermoid carcinoma--15 years experience.
Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patient's prognosis and the tumour's histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer. A retrospective analysis of the medical records of patients diagnosed with mucoepidermoid carcinoma of the lung between 1991 and 2006 was conducted. The study comprised 15 patients. Higher histological grade tumours had a higher proportion of squamoid cells (P = 0.019); the tumours of patients with lymph node metastases also had a higher proportion of squamoid cells than did the tumours of patients without lymph node metastases (P = 0.015). Patients with early stage tumours (stage IA, IB, IIB) had better outcomes (10-year survival rate = 87.5%), than did patients with late-stage tumours (stage IIIB, IV) (1-year survival rate = 28.6%; 2-year survival rate = 0%, P = 0.001). Patients with lower-grade tumours (grade 1 and grade 2) had better outcomes (1-year survival rate = 80%; 5-year survival rate = 57.1%) than did patients with higher-grade tumours (grade 3) (1-year survival rate = 20%, P = 0.035). Tumour staging was a significant independent predictor of survival on Cox proportional hazards analysis. The proportion of squamoid cells on tumour histology may be an indicator of the level of tumour malignancy. Tumour, node, metastasis staging is a significant determinant of prognosis in patients with tracheobronchial mucoepidermoid carcinoma.


Natural Immunosuppressants as a Treatment for Chronic Insomnia Targeting the Inflammatory Response Induced by NLRP3/caspase-1/IL-1β Axis Activation: A Scooping Review.
Chronic insomnia is an inflammatory-related disease with an important pathological basis for various diseases which is a serious threat to a person's physical and mental health. So far, many hypotheses have been proposed to explain the pathogenesis of insomnia, among which inflammatory mechanisms have become the focus of scientific attention. In this regard, the aim of the present scooping review is to evaluate the potential benefits of natural compounds in treatment of chronic insomnia targeting nucleotide-binding oligomerization domain (NOD)-like receptor-pyrin-containing protein 3 (NLRP3)/caspase-1/IL-1β axis as one of the most important activators of inflammatory cascades. The data show that compounds that have the potential to cause inflammation induce sleep disorders, and that inflammatory mediators are key molecules in regulating the sleep-related activity of neurons. In the inflammatory process of insomnia, the role of NLRP3 in the pathogenesis of insomnia has been gradually considered by researchers. NLRP3 is an intracellular sensor that recognizes the widest range of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). After identification and binding to damage factors, NLRP3 inflammasome is assembled to activate the caspase-1 and IL-1β. Increased production and secretion of IL-1β may be involved in central nervous system dysregulation of physiological sleep. The current scooping review reports the potential benefits of natural compounds that target NLRP3 inflammasome pathway activity and highlights the hypothesis which NLRP3 /caspase-1/IL-1β may serve as a potential therapeutic target for managing inflammation and improving symptoms in chronic insomnia.


First divertor Thomson scattering measurements on MAST-U.
MAST-U is equipped with a Super-X divertor, which aims to reduce heat flux to the target and promote detachment. Measurements of plasma electron density and temperature in the Super-X chamber offer insight into the processes at work in this type of divertor. First data have been obtained from the MAST-U divertor Thomson scattering diagnostic designed to measure these quantities. Following a Raman scattering calibration in nitrogen, the diagnostic operated over a number of plasma pulses in the first physics campaign. Electron density and temperature measurements have been taken in attached and detached conditions as the strike leg moved through the field of view of the diagnostic. The system operated with a dedicated 30 Hz laser with timing synchronized to seven similar lasers installed in the core Thomson system. Electron densities in the range of 1 × 1018-5 × 1019 m-3 have been measured by the system throughout these regimes. Although the system was specified to measure from 1 to 40 eV, electron temperatures in the Super-X divertor in the first campaign were low, and measurement down to 0.5 eV has been critical, particularly close to the detachment front. This generation of polychromator has been designed with increased stray light rejection compared to those used in the core system. This has proved successful with very low levels of stray light observed.


Gregariousness versus solitude: another look at parasite faunal richness in Canadian freshwater fishes.
Recently Poulin (1991), using published data on Canadian freshwater fishes (60 species, three families), concluded that there is no difference in parasite species numbers between solitary and social species. Nor could he associate parasite diversity to host size, age or range of distribution. Analysing Poulin's data with somewhat differing methods I reached different conclusions. Recognising that reported parasite species number per host species is a function of research effort (also noted by Poulin), I use residuals of the regression model as a measure of standardized parasite species number. First, it turned out that solitary and social salmonids differ in parasite faunal richness. That is, solitary species harbour a smaller diversity than species that school outside the breeding season. Second, host distribution range clearly correlates with the richness of total parasite fauna of the species in the three families. This observation was recently confirmed for North American freshwater fish species by Chandler and Cabana (1991). Third, in Percidae host size and age are also correlated with parasite species diversity.


Decreased Sox2 Messenger RNA Expression in Basal Cell Carcinoma.
Sox2, zeb1, and p21 have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma. However, their expression level in basal cell carcinoma (BCC) has not been elucidated. We hypothesized BCC, contrary to SCC, and melanoma, could be a suitable model to study mechanisms which attenuate tumor metastasis. The aim of this study was to examine the messenger RNA (mRNA) expression levels of sox2, zeb1, and p21 in BCC. Twenty-seven nonmetastatic BCC and twelve normal skin samples were evaluated using real-time reverse transcriptase polymerase chain reaction. The stemness marker sox2 demonstrated marked down-regulation, but zeb1 and p21 showed no significant change. Here, we report a negative association between sox2 mRNA expression level and nonmetastatic BCC, thus, providing a likely explanation for the fact that normal skin is more reliant on sox2 than BCC. BCC may be using decreased sox2 mRNA to remain incognito from metastatic potential.


The Emerging Network of Mitochondria-Organelle Contacts.
Membrane contact sites between mitochondria and other organelles are important for lipid and ion exchange, membrane dynamics, and signaling. Recent advances are revealing their molecular features and how different types of mitochondria contacts are coordinated with each other for cell function.


Quantitative analysis of sterols in serum by high-performance liquid chromatography. Application to the biochemical diagnosis of cerebrotendinous xanthomatosis.
A method for the simultaneous determination of 5 alpha-cholestan-3 beta-ol and cholesterol in serum by high-performance liquid chromatography was developed. After addition of internal standard (5 beta-cholestan-3 alpha-ol) and saponification with ethanolic potassium hydroxide, the sterols were converted into their benzoyl derivatives, which were subjected to reversed-phase liquid chromatography with ultraviolet detection at 228 nm. Only 0.1 ml of serum was needed to give a reproducible result. This method has been used for the biochemical diagnosis of cerebrotendinous xanthomatosis, a hereditary disorder of cholesterol metabolism.


Phage infection in vaginal lactobacilli: an in vitro study.
During bacterial vaginosis, an unexplained decrease of vaginal lactobacilli occurs. To identify whether these lactobacilli could be infected by phages, we isolated phages from vaginal lactobacilli and analyzed their potential virulence in attacking vaginal lactobacilli in vitro. Vaginal samples were obtained from 39 reproductive-aged women. The selective Rogosa SL agar was used to isolate lactobacilli, from which phages induced by mitomycin C or released spontaneoulsy were analyzed by the agar spot method. Of 20 samples from women with vaginal infections, 12 did not have lactobacilli. From the remaining 8 infection samples and the 19 samples from healthy women, 37 Lactobacillus strains were isolated, from which 7 temperate phages were identified. Upon analysis, all 7 phages infected vaginal lactobacilli from the same and/or different women in vitro. Two phages, Phikc005 and Phikc007, had a broad host range, infecting 7 of 8 species tested. A control intestinal Lactobacillus phage also lysed several vaginal strains. One vaginal phage, Phikc039, was apparently lytic against vaginal lactobacilli from 7 other women. This phage was characterized as follows: plaque morphology, small and clear; burst size, 300 phages per cell; spontaneous induction rate, 1 per 10(6) cells; DNA, double-stranded and linear, 41 kb; and shape, a hexogonal head and a non-contractile tail. Bacteriophages were isolated from vaginal lactobacilli of some women and were shown in vitro to lyse vaginal Lactobacillus strains from the same and/or different women. It was suggested that vaginal lactobacilli might be suppressed by phages.


Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR.
Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I-BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I-BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I-BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I-BABP-bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. The coordinates of the 10 lowest energy structures of the human I-BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3.


Extension of the ELISA method to the measurement of the specific radioactivity of viruses in crude cellular extracts.
The double-antibody sandwich method of ELISA, which allows accurate quantitative determination of plant viruses, was extended to a radiochemical procedure which permits direct measurement of the specific radioactivity of virus labelled in vivo and present in very crude plant homogenates. Evidence is presented showing that 20 to 50% of the virus introduced in the polystyrene wells during the antigen incubation step could be trapped in the sandwich. The percentage of virus bound increased with the concentration of the coating antibody and was almost proportional to the concentration of the antigen and to the incubation time of the antigens. Complete dissociation of the double-antibody sandwich was achieved by incubation with 0.2 M KOH or NaOH (pH 13.3), and the label carried by the virus was measured by scintillation counting of the solubilization fluid. The ratio infected/healthy was much higher for the radiochemical procedure than for the immunosorbent assay itself since binding of the virus to the coating antibody was not accompanied by any nonspecific trapping of radioactive contaminants in the double-antibody sandwich. The procedure was highly sensitive since the background corresponded to the scintillation counting background. The detection of label carried by tobacco mosaic virus was possible when the tobacco samples contained at least 5 ng of virus carrying a label as low as 40 dpm 3H or 20 dpm 14C.


Reduced cisplatin sensitivity of head and neck squamous cell carcinoma cell lines correlates with mutations affecting the COOH-terminal nuclear localization signal of p53.
Head and neck squamous cell carcinomas (HNSCC) are the most frequent malignancies of the upper aerodigestive tract. Cisplatin resistance is a major problem in the treatment of a large number of HNSCC cancer patients. In this study, nine randomly selected HNSCC cell lines were investigated regarding expression, presence of mutations, nucleocytoplasmic distribution of p53, and sensitivity to cisplatin. Protein expression was evaluated by Western blot analysis. The whole open reading frame of p53 was determined by reverse transcription-PCR sequencing. Nucleocytoplasmic distribution was evaluated by confocal laser scanning microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay was used to test for cisplatin sensitivity. p53 mutations were found in all nine investigated HNSCC cell lines. Nuclear p53 signal was detected in six cell lines, whereas three cell lines exhibited total loss of nuclear p53 signal. Nuclear signal depended on the presence or absence of the COOH-terminal nuclear localization signal in p53. Cisplatin sensitivity was highly reduced in the group with loss of nuclear p53 signal compared with those with detectable nuclear signal. Transfection of wild-type and mutant p53 into a rat embryonic cell system showed highly reduced activity of the nuclear localization signal mutant p53 protein. Taken together, these data suggest that "loss of nuclear p53 signal" correlates with cisplatin resistance in HNSCC. If these results can be validated on a larger number of tumor samples, including fresh tumor tissues, it potentially could help in sparing a subgroup of HNSCC patients the side effects associated with unnecessary chemotherapy by identifying cisplatin nonresponders before chemotherapy induction.


Delivering Sprinkles Plus through the Integrated Child Development Services (ICDS) to reduce anemia in pre-school children in India.
To assess the effectiveness of micronutrient powder (MNP) supplementation in reducing anemia levels in children aged 6 mo to 6 y in India. Sixty sachets of MNP (Sprinkles Plus) were administered flexibly over a 4 mo period to 17,124 children at anganwadi centers or at home through Integrated Child Development Services (ICDS). Compliance was monitored using compliance cards and an assessment of mother's recall at post-intervention survey. Hemoglobin was measured in separate random samples of 1,786 children before and 1,782 children after MNP supplementation. Mean compliance rate was estimated at 56.4 % (based on mother's recall) and 91.7 % (based on compliance cards) for children who received MNP at home. Mean compliance was 96.9 % (based on compliance cards) for children who received MNP at anganwadis. A significant reduction in anemia (50 % to 33 % in boys; p-value <.000; 47.4 % to 34.2 % in girls) was seen following MNP supplementation. Integration of a flexibly administered MNP supplementation into the ICDS is effective in reducing and treating anemia in children 6 mo to 6 y age.


Epidemiology of admissions to 11 stand-alone high-dependency care units in the UK.
High-dependency care units (HDUs) are a focus of research to optimize critical care resource allocation. HDUs provide a level of care between the general ward and the intensive care unit (ICU). However, few data report on the case mix and outcomes of patients in these units. Retrospective observational cohort study of patients admitted to 11 stand-alone HDUs in the UK from 2008 to 2011. We stratified patients by location prior to HDU admission and location on discharge from HDU, and we summarized the case mix, transitions of care, and mortality. Of 9008 patients admitted to 11 stand-alone HDUs, 56.5% were male and the mean age was 62.7 ± 17.9 years. The majority of patients admitted to HDUs were non-surgical (59.3%), with 22.4 and 20.1% admitted from the ICU and general ward, respectively; 41.3% were admitted from the operating room or recovery suite. The median length of stay in HDU was 1.8 days (IQR 0.9-3.5) and in-HDU mortality was 5.1%. Among HDU survivors (n = 8551), 8.5% were discharged to an ICU, 80.9% to a general ward, and 10.6% to other care areas. For patients admitted to HDU from an ICU, only 5.8% were readmitted to ICU. Hospital mortality for the HDU population was 14.8%; for patients discharged to an ICU, hospital mortality was 43.6%. In a sample of 11 stand-alone HDUs in the UK, patients are from many different hospital locations. Hospital mortality for patients requiring HDU care is high, particularly for patients who require transfer to an ICU.


Simple method for production of randomized human tenth fibronectin domain III libraries for use in combinatorial screening procedures.
Challenges such as the rapid development of detection reagents for emerging or engineered pathogens, the goal of identifying probes for every protein in the human proteome, and the development of therapeutic molecules require systems for development of epitope binding molecules that are faster and cheaper than conventional antibody development. To be practical and effective, antibody mimics must be small, stable molecules that contain exposed loops or surfaces that can be randomized and screened using selective combinatorial assays. The tenth human fibronectin type III domain (10Fn3) fits these requirements and has recently been developed as an antibody mimic for use in detection and therapeutic platforms. Previously described systems for working with 10Fn3 used PCR-based approaches to anneal multiple oligonucleotides to generate randomized 10Fn3 libraries. Here we describe a simplified approach for creating randomized 10Fn3 libraries and report the first use of a T7-based phage display system for screening these libraries.


Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage.
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of brain edema formation after experimental subarachnoid hemorrhage (SAH). In this study, we evaluated the effect of anti-VEGF antibody neutralization on brain edema formation after experimental SAH in mice. Mice underwent sham operation or filament puncture SAH and were assigned to sham, SAH + vehicle, or SAH + anti-VEGF antibody groups. Vehicle or anti-VEGF antibody was administrated by an intracerebroventricular injection at 30 min post-SAH. After 24 h of SAH modeling, neurological score was recorded to evaluate neurobehavioral functions, brain water content was calculated to assess the level of brain edema, and immunohistochemistry of immunoglobulin (Ig) G was performed to evaluate the permeability of the blood-brain barrier (BBB). Anti-VEGF antibody significantly ameliorated neurological score and brain edema after SAH compared with the SAH + vehicle group. Immunohistochemistry showed that post-SAH IgG extravasation in brain tissue was suppressed by anti-VEGF antibody. This study suggests that VEGF is involved in brain edema formation after SAH, and that anti-VEGF antibody can decrease BBB permeability, suppress brain edema formation, and improve functional outcome after 24 h of SAH.


Clinical triggers and vital signs influencing crisis acknowledgment and calls for help by anesthesiologists: A simulation-based observational study.
In a perioperative emergency, anesthesiologists must acknowledge the unfolding crisis promptly, call for timely assistance, and avert patient harm. We aimed to identify vital signs and qualitative factors prompting crisis acknowledgment and to compare responses between observers and participants in simulation. Prospective, simulation-based, observational study. An anesthesia crisis resource management course at a freestanding simulation center. Sixty attending anesthesiologists from a variety of practice settings. In each case, a primary anesthesiologist in charge (PAIC) managed a simulated patient undergoing a uniformly scripted sequence of perioperative anaphylaxis and called for help from another anesthesiologist when a crisis began. Anesthesiologist observers (AOs) viewed the case separately and recorded times of crisis onset. Simulation footage was reviewed by investigators for patient vital signs and participant behaviors at times of crisis acknowledgment, with the call for help as an explicit proxy for PAIC crisis acknowledgment. These factors were categorized, and group-level data were compared. Nineteen PAICs and 41 AOs were included. Clinicians acknowledged crises around a mean arterial pressure (MAP) of 65 mmHg and oxygen saturation of 94% as anaphylactic shock progressed. PAICs acknowledged crises at a higher respiratory rate than AOs (20 vs. 18 breaths/min, p = 0.038). Other vitals and timing of crisis acknowledgment did not differ between PAICs and AOs. Nearly half of all participants (45%) identified crises at MAP <65 mmHg. Timing of crisis acknowledgment varied widely (range: 421 s). Despite overall heterogeneity in clinical performance, anesthesiologists acknowledged crises per standard definitions of hypotension. Thresholds for crisis acknowledgment did not significantly differ between PAICs and AOs, suggesting minimal effect from active care responsibility. Many indicated crises at MAP <65 mmHg or after significant deterioration, risking failure-to-rescue events. We suggest that crisis management instruction should address triggers for requesting help.


Monomeric insulins obtained by protein engineering and their medical implications.
The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.


Assessment of rice yield loss due to exposure to ozone pollution in Southern Vietnam.
The study domain covered the Eastern region of Southern of Vietnam that includes Ho Chi Minh City (HCMC) and five other provinces. Rice production in the domain accounted for 13% of the national total with three crop cycles per year. We assessed ozone (O3) induced rice production loss in the domain for 2010 using simulated hourly surface O3 concentrations (WRF/CAMx; 4km resolution). Simulated O3 was higher in January-February (largely overlaps the first crop) and September-December (third crop), and lower in March-June (second crop). Spatially, O3 was higher in downwind locations of HCMC and were comparable with observed data. Relative yield loss (RYL) was assessed for each crop over the respective growing period (105days) using three metrics: AOT40, M7 and flux-based O3 dose of POD10. Higher RYL was estimated for the downwind of HCMC. Overall, the rice production loss due to O3 exposure in the study domain in 2010 was the highest for the first crop (up to 25,800metrictons), the second highest for the third crop (up to 21,500tons) and the least for the second crop (up to 6800tons). The low RYL obtained for the second crop by POD10 may be due to the use of a high threshold value (Y=10nmolm(-2)s(-1)). Linear regression between non-null radiation POD0 and POD10 had similar slopes for the first and third crop when POD0 was higher and very low slope for the second crop when POD0 was low. The results of this study can be used for the rice crop planning to avoid the period of potential high RYL due to O3 exposure.


Radiographic assessment of skeletal maturation stages for orthodontic patients: hand-wrist bones or cervical vertebrae?
The skeletal maturation status of a growing patient can influence the selection of orthodontic treatment procedures. Either lateral cephalometric or hand-wrist radiography can be used to assess skeletal development. In this study, we examined the correlation between the maturation stages of cervical vertebrae and hand-wrist bones in Taiwanese individuals. The study group consisted of 330 male and 379 female subjects ranging in age from 8 to 18 years. A total of 709 hand-wrist and 709 lateral cephalometric radiographs were analyzed. Hand-wrist maturation stages were assessed using National Taiwan University Hospital Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages were determined by the latest Cervical Vertebral Maturation Stage (CVMS) Index. Spearman's rank correlation was used to correlate the respective maturation stages assessed from the hand-wrist bones and the cervical vertebrae. The values of Spearman's rank correlation were 0.910 for males and 0.937 for females, respectively. These data confirmed a strong and significant correlation between CVMS and NTUH-SMI systems (p less than 0.001). After comparison of the mean ages of subjects in different stages of CVMS and NTU-SMI systems, we found that CVMS I corresponded to NTUH-SMI stages 1 and 2, CVMS II to NTUH-SMI stage 3, CVMS III to NTUHSMI stage 4, CVMS IV to NTUH-SMI stage 5, CVMS V to NTUH-SMI stages 6, 7 and 8, and CVMS VI to NTUH-SMI stage 9. Our results indicate that cervical vertebral maturation stages can be used to replace hand-wrist bone maturation stages for evaluation of skeletal maturity in Taiwanese individuals.


MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor of the extremities.
To determine diagnostic performance of MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor (ALT) of the extremities. This retrospective study was performed at three tertiary sarcoma centers and included 150 patients with surgically treated and histology-proven lesions. The training-validation cohort consisted of 114 patients from centers 1 and 2 (n = 64 lipoma, n = 50 ALT). The external test cohort consisted of 36 patients from center 3 (n = 24 lipoma, n = 12 ALT). 3D segmentation was manually performed on T1- and T2-weighted MRI. After extraction and selection of radiomic features, three machine learning classifiers were trained and validated using nested fivefold cross-validation. The best-performing classifier according to previous analysis was evaluated and compared to an experienced musculoskeletal radiologist in the external test cohort. Eight features passed feature selection and were incorporated into the machine learning models. After training and validation (74% ROC-AUC), the best-performing classifier (Random Forest) showed 92% sensitivity and 33% specificity in the external test cohort with no statistical difference compared to the radiologist (p = 0.474). MRI radiomics-based machine learning may classify deep-seated lipoma and ALT of the extremities with high sensitivity and negative predictive value, thus potentially serving as a non-invasive screening tool to reduce unnecessary referral to tertiary tumor centers.


[DETECTION OF VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS RNA IN BIOLOGICAL SAMPLES BY REVERSE-TRANSCRIPTION POLYMERASE CHAIN REACTION].
Detection-and identification of Venezuelan equine encephalomyelitis (VEE) virus RNA in biological samples by reverse-transcription polymerase chain reaction (RT-PCR) and RT-PCR in real time (rRT-PCR). VEE, Sindbis, West Nile, Japanese and tick-borne encephalitis viruses were studied. Cell culture of chicken fibroblasts, outbred mice and rats, Javanese macaques were used in the experiments. Biological activity determination of the running culture of causative agents used in the experiments was carried out by negative colony method in monolayer cell culture under agar coating. and using intra-cerebral infection of mice. Reagent kits developed in the 48th Central Research Institute and Institute of Analytical Instrument Engineering were used during execution of experiments of VEE virus RNA detection by RT-PCR and rRT-PCR. VEE virus was detected in biological samples by various methods. Data from RT-PCR and rRT-PCR are in accordance with the results of virus detection in samples using sensitive animals. Use of molecular-diagnostics methods for detection in biological samples of a causative agent of a dangerous infectious disease is important for procuring biological safety of Russian Federation.


Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.
Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies.


Shared reading: Parental attitudes, practices and barriers in Turkey.
Understanding the nature of parent-child shared reading (SR) practices is important to reach children's developmental potential and subsequent achievement. We evaluated the parental attitudes and practices, associated variables and barriers related to SR. This prospective study enrolled 624 parents of children aged 1-72 months who presented to a tertiary hospital for well-child care or acute minor illness. Face-to-face interviews were conducted using a questionnaire. The median age for starting SR was 12 (0-72) months. Daily SR activities were provided by 29.5% of the parents. Owning >10 children's books, higher socioeconomic status, attending pre-school/kindergarten and being a single child were associated with daily reading (P < 0.001). In total, 36.5% of the parents reported that they had not yet started SR and planned to start SR when their children reached a median age of 20.5 (2-72) months. The most commonly reported barriers were time constraints and the perception that their child was too young. Almost 10% of the parents had received an SR recommendation. Parents who had received a recommendation and those who had a habit of self-reading multiple times a week were more likely to begin SR at younger child age and to read daily (P < 0.001). This study demonstrated low rates of parent-child SR activities in early childhood, particularly in the first years of life, in Turkey. Our findings emphasise the need for a national strategy integrated into the healthcare system to promote SR.


Inhibitory effect of 5-methoxy-N,N-dimethyltryptamine on the synaptosomal uptake of 5-hydroxytryptamine.
5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) in concentrations of 0.5-500 microM produced a significant inhibition of [14C]5-hydroxytryptamine [14C]5-HT) uptake in striatal, hippocampal and hypothalamic crude synaptosomes from rat brain. Higher concentrations of 5-MeODMT (10 microM) also inhibited the uptake of [3H]dopamine [3H]DA) and induced the release of [14C]5-HT and [3H]DA from preloaded synaptosomes. It appears that the 5-HT agonist properties of 5-MeODMT may involve reuptake inhibition in addition to the previously documented direct receptor stimulation.


miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review.
Head and neck cancers include epithelial tumors arising in the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity. Metastasis is a hallmark of cancer. MicroRNAs (miRNAs) are endogenous small non-coding RNAs involved in cell proliferation, development, differentiation and metastasis. It is believed that miRNA alterations correlate with initiation and progression of cancer cell proliferation or inhibition of tumorigenesis. Moreover, miRNAs have different roles in development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). Altered expression of miRNAs could be novel molecular biomarkers for the definite diagnosis of cancer, metastatic site, cancer stage, and its progression. The purpose of this review was to provide a comprehensive literature review of the role of miRNAs in head and neck cancer metastasis. A relevant English literature search in PubMed, ScienceDirect, and Google Scholar was performed. The keywords 'miRNA', 'head and neck', and 'cancer' were searched in title and abstract of publications; limited from 1990 to 2015. The inclusion criterion was the role of miRNAs in cancer metastasis. The exclusion criterion was the other functions of miRNAs in cancers. Out of 15221 articles, the full texts of 442 articles were retrieved and only 133 articles met the inclusion criteria. Despite the advances in cancer treatment, the mortality rate of HNSCC is still high. The potential application of miRNAs for cancer therapy has been demonstrated in many studies; miRNAs function as either tumor suppressor or oncogene. The recognition of metastamir and their targets may lead to better understanding of HNSCC oncogenesis, and consequently, development of new therapeutic strategies which is a necessity in cancer treatment. Development of therapeutic agents based on miRNAs is a promising target.


Prediction of Adverse Effects of Drug-Drug Interactions on Cardiovascular System Based on the Analysis of Structure-Activity Relationships.
Co-administration of drugs often leads to drug-drug interactions, which could be accompanied by various adverse drug reactions that pose a threat to life and health of the patient. The effect caused by adverse drug reactions on cardiovascular system is one of the most significant manifestations of drug-drug interaction. Clinical assessment of adverse drug reactions resulting from drug-drug interaction between all drug pairs used in therapeutic practice is not possible. The purpose of this work was to build models using structure-activity analysis to predict adverse effects of drugs on cardiovascular system, mediated by pairwise interactions between the drug pairs when they are taken together. Data on the adverse effects resulting from drug-drug interaction were obtained from the DrugBank database. The data on drug pairs that do not cause such effects, which are necessary for building accurate structure-activity models, were obtained from the TwoSides database, which contains the results of analysis of the spontaneous reports. Two types of descriptors were used to describe a pair of drug structures: PoSMNA descriptors and probabilistic estimates of the prediction of biological activities obtained using the PASS program. Structure-activity relationships were established using the Random Forest method. Prediction accuracy was calculated by means of five-fold cross-validation. The highest accuracy values were obtained using PASS probabilistic estimates as descriptors. The area under the ROC curve was 0.94 for bradycardia, 0.96 for tachycardia, 0.90 for arrhythmia, 0.90 for ECG QT prolongation, 0.91 for hypertension, 0.89 for hypotension.


Antigenic comparison of swine influenza virus isolates.
Cross hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests demonstrated strong antigenic relationship between A/Swine/Wisconsin/1/73 (SW/73) and A/Swine/Shope/15/31 (SW/31) influenza viruses. An eigthyone fold purification of virus was achieved by adsorption and elution followed by differential ultracentrifugation and sedimentation through linear sucrose gradient. Radioimmunoassay using purified 125I labeled viral antigens revealed antigenic variation between the two virus isolates. Neuraminidase of both viruses had pH optima between 6.5 and 7.0, and SW/31 enzyme was relatively more heat stable than SW/73.


Cortical responses associated with the preparation and reaction to full-body perturbations to upright stability.
To examine the cortical activity associated with 'central set' preparations for induced whole-body instability. Self-initiated and temporally unpredictable perturbations to standing balance were caused by the release of a load coupled to a cable affixed to a harness while participants stood on a force plate. Electroencephalographic and electromyographic signals were recorded. Peak activity was located at the Cz electrode. The predictable condition elicited a DC shift 950 ms prior to perturbation onset and was 18.0+/-10.5 micro V in magnitude. Pre-perturbation activity was not associated with the motor act of perturbation initiation and was dissociable from cortical activity related to anticipatory postural muscle activation. Following perturbation onset, N1 potentials were observed with a peak amplitude of 17.6+/-7.2 micro V and peak latency of 140.1+/-25.9 ms. In unpredictable trials, pre-perturbation activity was absent. The peak amplitude (32.0+/-14.8 micro V) and latency (156.5+/-11.8 ms) of the post-perturbation N1 potential were significantly larger (p=0.002) and later (p<0.001) than for predictable trials. Self-initiated postural instability evokes cortical activity prior to and following perturbation onset. Pre-perturbation cortical activity is associated with changing central set to modulate appropriate perturbation-evoked balance responses. These findings establish a link between reactive balance control and cortical activity that precedes and follows perturbations to stability.


Multiple carboxylase deficiency.
1. The multiple carboxylase deficiencies are inborn errors in the metabolism of biotin in which there is defective activity of propionyl CoA carboxylase, 3-methylcrotonyl CoA carboxylase and pyruvate carboxylase. 2. Two distinct disorders have been described. 3. In one the fundamental defect is in the enzyme holocarboxylase synthetase which catalyzes the molecular activation of the apocarboxylase proteins. 4. In the other the fundamental defect is in biotinidase which catalyzes the reutilization of biotin and may be involved in its digestion and intestinal absorption.


Isolation, characterization and partial amino acid sequence of a phosphorylated polypeptide (E4) from bovine embryonic dental enamel.
A phosphorylated polypeptide (E4) of molecular weight 5000-6000, has been isolated from bovine embryonic enamel by Bio-Gel P-10 gel filtration and DE-52 ion-exchange chromatography. The peptide contains three serine residues all of which are phosphorylated. All three O-phosphoserine residues are in glutamic acid-O-phosphoserine-tyrosine sequences that are distributed relatively evenly along the polypeptide chain. Although it was not possible to sequence the entire polypeptide chain directly by automatic peptide sequencing, a partial sequence and peptide map was constructed on the basis of the sequence and composition of peptides derived by cyanogen bromide, trypsin and chymotrypsin digestion. The presence of glutamic acid, tyrosine and leucine adjacent to and near the O-phosphoserine residues may be important in calcium binding and in mineralization.


[Dialysis patients in intensive care units].
The number of dialysis patients needing intensive medical care is steadily increasing, mostly due to cardiovascular diseases. Of the patients 50% are admitted due to myocardial infarction, malignant arrhythmia or acute cardiac failure and many also due to hyperkalemia and acute volume overload against the background of anuria or oligouria associated with arterial hypertension and hypervolemic hypertensive pulmonary edema. The treatment of an acute cardiac syndrome is comparable to the treatment of patients with healthy kidneys and despite the significantly higher cardiovascular mortality of these patients the acute prognosis is not significantly different to non-dialysis patients. In association with hypervolemic hypertensive pulmonary edema and all forms of hyperkalemia, dialysis treatment is always necessary. In the case of complications due to infections, in particular septicemia, dialysis patients seem to profit from the general therapy guidelines for septic patients, such as early goal-directed therapy. Underdosing of antibiotics for dialysis patients with sepsis represents a substantial problem in the clinical practice and can additionally endanger these patients.


Induction of M-phase entry of prophase-blocked mouse oocytes through microinjection of okadaic acid, a specific phosphatase inhibitor.
We report that a specific inhibitor of types 1 and 2A phosphatases, okadaic acid (OA), induces germinal vesicle break down (GVBD) and chromosome condensation when microinjected into denuded mouse oocytes maintained in prophase block by analogs of cAMP, inhibitors of phosphodiesterase, or a tumor-promoting phorbol ester. GVBD and chromosome condensation are also observed when incompetent oocytes are similarly injected with OA, this effect being dependent on the oocyte diameter. Marked changes in cell shape, cytoskeletal organization, and chromosome condensation with abnormal or abortive spindle formation are associated with such injections. The polar body is not formed. These results led to the conclusions that in mouse oocytes, OA acts distal to both the cAMP-modulated pathway involved in meiotic arrest and the inhibitory action exerted by tumor-promoting phorbol esters.


SIUMB recommendations on the use of ultrasound in neoplastic lesions of the gallbladder and extrahepatic biliary tract.
Extrahepatic biliary tract and gallbladder neoplastic lesions are relatively rare and hence are often underrepresented in the general clinical recommendations for the routine use of ultrasound (US). Dictated by the necessity of updated summarized review of current literature to guide clinicians, this paper represents an updated position of the Italian Society of Ultrasound in Medicine and Biology (SIUMB) on the use of US and contrast-enhanced ultrasound (CEUS) in extrahepatic biliary tract and gallbladder neoplastic lesions such as extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, gallbladder adenomyomatosis, dense bile with polypoid-like appearance and gallbladder polyps.


Safety and pharmacokinetics of multiple doses of aclidinium bromide administered twice daily in healthy volunteers.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and increased cholinergic tone. The global initiative for chronic obstructive lung disease (GOLD) guidelines recommend long-acting anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel, long-acting muscarinic antagonist developed for the treatment of COPD. A phase I, randomized, single-blind, multiple-dose clinical trial was conducted to assess the safety and pharmacokinetics (PK) of multiple doses of twice-daily (BID) aclidinium in healthy subjects. Thirty healthy male and female subjects received aclidinium 200 μg, 400 μg, 800 μg, or placebo twice daily for 7 days. Subjects were randomized to 1 of 3 cohorts and 10 subjects in each cohort were randomized (8:2) to either aclidinium or placebo groups. Safety was assessed via adverse events (AEs), laboratory evaluations, vital signs, and ECGs. Plasma samples were obtained at multiple time points throughout the study and analyzed for aclidinium and its inactive acid and alcohol metabolites using a fully validated method of liquid chromatography coupled with tandem mass spectrometry. A total of 9 treatment-emergent AEs were reported (1, placebo; 3, aclidinium 400 μg; 5, aclidinium 800 μg), all of which were mild in severity. No serious AEs were reported. There were no clinically meaningful changes in laboratory parameters or vital signs. PK parameters on Day 7 following BID dosing of aclidinium showed that steady state was achieved for aclidinium and its metabolites. On Days 1 and 7, maximum plasma concentrations (Cmax) of aclidinium were generally observed at the first PK time point (5 min postdose) and rapidly declined, with plasma concentrations generally less than 10% of Cmax by 6 h postdose in all aclidinium groups. Mean effective t(½) after the evening dose on Day 7 ranged from 4.6 to 7.0 h for aclidinium 400 μg and 800 μg, similar to the terminal t(½) observed on Day 1 (4.5-5.9 h). Exposure for aclidinium and both metabolites increased with increasing dose, with the increase in exposure being less than dose proportional between the 400 μg and 800 μg doses. Overall, all doses of aclidinium were safe and well tolerated throughout the study. Pharmacokinetic steady state was reached for aclidinium and both metabolites within the 7-day treatment period for all doses tested. Aclidinium bromide exhibited time-independent PK following dosing to steady state, indicating that similar concentration versus time profiles will occur after repeated administration at the same dose and frequency.


Current Clinical Applications of Testicular Cancer Biomarkers.
Current use of testicular biomarkers for screening, diagnosis, and follow-up is reviewed in the context of potential clinical utility of these tests. This information will be of value to clinicians to determine patient suitability for certain treatments and will also assist in reviewing current literature regarding potential biomarkers that may be used for testicular cancer.


[Lung cancer with metastasis to pituitary gland].
To improve the diagnostic accuracy of lung cancer with metastasis to pituitary gland. The clinical data of 6 cases with lung cancer metastatic to pituitary gland were reviewed retrospectively and the features of clinical manifestations and sella MRI image analyzed. (1) The patients had an average of 57.5 years of age. (2) Most of them had 2 additional metastatic sites other than pituitary gland. (3) Posterior lobe is mostly effected and the most common symptom is diabetes insipidus. The image of sella MRI had some special characteristics. (4) Pituitary anterior lobe function is often impaired in some degree. Lung cancer is one of the commonest primary tumor with metastasis to pituitary gland and thorough exploration for primary cancer should be carried out in elderly patients with new onset of diabetes insipidus.


Conserving forest insect biodiversity requires the protection of key habitat features.
Loss of insect biodiversity is widespread, and in forests habitat loss is one of the major drivers responsible. Integrative forest management must consider the preservation and promotion of key habitat features that provide essential microhabitats and resources to conserve biodiversity alongside ecosystem functions and services.


Rethinking calcium profiles around single channels: the exponential and periodic calcium nanodomains.
Many fundamental calcium-dependent physiological processes are triggered by high local calcium levels that are established around the sites of calcium entry into the cell (channels). They are dubbed as calcium nanodomains but their exact profiles are still elusive. The concept of calcium nanodomains stems from a linear model of calcium diffusion and is only valid when calcium increases are smaller than the concentration of cytoplasmic buffers. Recent data indicates that much higher calcium levels cause buffer saturation. Therefore, I sought explicit solutions of a nonlinear reaction-diffusion model and found a dichotomous solution. For small fluxes, the steady state calcium profile is quasi-exponential, and when calcium exceeds buffer concentration a spatial periodicity appears. Analytical results are supported by Monte-Carlo simulations. I also imaged 1D- and radial calcium distributions around single α-synuclein channels in cell-free conditions. Measured Ca profiles are consistent with theoretical predictions. I propose that the periodic calcium patterns may well arise under certain conditions and their specific functional role has to be established.


[Primary immune thrombocytopenia in adults: diagnostics and treatment consensus statement of the Austrian Society of Hematology and Oncology (ÖGHO)].
Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).


Polypharmacy, chronic kidney disease, and incident fragility fracture: a prospective cohort study.
Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status. Participants were 2023 patients (55% men; mean age, 69 years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders. Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6 years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96-1.79) and 1.99 (1.35-2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction P = 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients. Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.


Comparative effectiveness of aerobic exercise versus Yi Jin Jing on ovarian function in young overweight/obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial.
Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disease among women of childbearing age, characterized by androgen excess and ovarian dysfunction. Aerobic exercise is an important solution used to manage PCOS, due to its multiple benefits. Yi Jin Jing is an important component of traditional Chinese exercise (TCE), based on the root of traditional Chinese medicine theory (TCM), which focuses on keeping the body as a whole in a harmonious state. However, to date there is no literature on the benign effects of Yi Jin Jing on PCOS. The primary purpose of this protocol is to assess the effectiveness of aerobic exercise versus Yi Jin Jing, on the management of ovarian function in young overweight/obese women with PCOS. The study will conduct a controlled randomized, superiority trial with three-arm parallel groups, recruiting 90 women diagnosed with PCOS, ages between 18 and 35 years, with a body mass index (BMI) ≥ 23 kg/m2. Women will be randomly assigned to either control group (combined oral contraceptives) or one of the intervention groups (Yi Jin Jing group or aerobic exercise group) with an allocation rate of 1:1:1. After randomization, the intervention will be conducted within a 12-week period. The primary outcome would be anti-Mullerian hormone (AMH) level; the secondary outcomes would be biochemical profiles, ovarian volume, antral follicle count, BMI, menstrual frequency, and homeostasis model assessment of insulin resistance (HOMA-IR). Outcome measures would be collected during baseline and end of treatment. Reporting of the study will follow the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. This proposed study will be the first randomized clinical trial to evaluate the comparative effectiveness of aerobic exercise versus Yi Jin Jing on the management of ovarian function in young overweight/obese women with PCOS. The results may provide a new evidence-based management strategy for young women with PCOS. Chinese Clinical Trial Registry ChiCTR1900022385 . Registered on 9 April 2019.


Low trait anxiety, high resilience, and their interaction as possible predictors for treatment response in patients with depression.
Although many demographic and clinical characteristics have been suggested to predict treatment outcome of depression, they provide only a weak prediction for clinical response. Based on the predictive values of trauma and biological markers involved in stress response, we investigated the roles of baseline trait anxiety and resilience, which were assumed as vulnerability and resilience factors, respectively, in predicting treatment response in naturalistically treated outpatients with depressive disorders. A total of 178 outpatients with depressive disorders were consecutively recruited and completed measures of trauma experiences, psychological symptoms, and resilience at baseline. Response was defined by Clinical Global Impression (CGI)-Improvement score ≤2 at last visit during a 6month-treatment period. Univariate analyses and multiple logistic regression analysis were performed to determine predictors of treatment response. Among demographic and clinical variables, treatment response was associated with increased age, longer treatment duration, higher resilience, and lower trait anxiety. In logistic regression analysis, resilience, trait anxiety, and their interaction significantly predicted treatment response after adjusting for age and treatment duration. Interaction between resilience and trait anxiety remained significant in the final model. Examining the interaction between the two, patients with low trait anxiety were only significantly affected by the level of resilience in response rate. Low trait anxiety, high resilience, and their interaction might contribute to better treatment response in depressed patients. Our result suggested that individual differences in responding to stress might be important in predicting treatment outcome of depression in addition to other demographic and clinical factors.


A malformed girl with a de novo proximal 6q deletion.
An additional case of interstitial deletion of chromosome 6, the first with breakpoints in q12 and q14, is reported. The female infant was the malformed first child of young, healthy parents. A review of proximal 6q deletions is made.


The effects of ACTH on lung maturation in fetal lambs.
The ability of adrenocorticotrophic hormone (ACTH) to induce lung maturation was evaluated in fetal lambs. One member of 14 twin pairs between 114 and 138 days of gestation was infused intravenously with 0.5 mg ACTH over 5 days. The lungs of treated versus control lambs were judged more mature by morphologic criteria by the use of light and electron microscopy and by biochemical criteria by the use of lamellar-body-rich cell fractions. None of 5 premature lambs treated with ACTH and allowed to breathe showed evidence of hyaline membrane disease, while 3 untreated control lambs showed typical hyaline membranes.


Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: implications for cellular-based therapy.
Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc-mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, β-galactosidase (β-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4(+) cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc-MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0-G1 phase, without significant differences between SSc and HC. SSc-MSCs showed an increased positive β-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, β-Gal staining increased significantly in SSc-MSCs. On the contrary, doxorubicin abolished p21 activation and elicited p53 induction both in SSc- and HC-MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-β-related transcripts and their protein levels were significantly higher in SSc-MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells, increasing surface expression of CD69 and restoring the regulatory function which is impaired in SSc. Increased activation of the IL-6 pathway observed in our cells might represent an adaptive mechanism to senescence, but preserving some specific cellular functions, including immunosuppression.


Short stature, craniofacial dysmorphism and dento-skeletal abnormalities in a large kindred. A variant of K.B.G. syndrome or a new mental retardation syndrome.
A possibly new mental retardation syndrome is described in a large family. The major features of the syndrome are: short statue, craniofacial dysmorphism and dento-skeletal abnormalities. The mode of inheritance of this syndrome appears to be autosomal dominant with a variable degree of expressivity. The possible similarity to another autosomally dominant inherited mental retardation syndrome, "the K.B.G. syndrome" as described by Hermann et al. (1975), is discussed.


Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission.
Patients with chronic lymphocytic leukemia (CLL) are considered in nodular partial remission (nPR) when they are in remission but bone marrow biopsies show rare nodules. The significance of the level of residual disease in nPR is not known. We studied 91 previously untreated CLL patients who were treated with fludarabine alone, fludarabine with prednisone, or fludarabine with cyclophosphamide and achieved nPR at the end of six courses. We compared bone marrow lymphoid infiltration before therapy and at the end of three and six courses of therapy as evaluated by a pathologist in retrospective fashion with that of the routine evaluation at the time of performing bone marrow biopsy. We then compared these results with those obtained by computer-aided histomorphometry in 28 patients in nPR. There was significant correlation (P < 0.05) between pathologists as well as between pathologists and histomorphometry. Upon correlation with clinical characteristics, there was significant correlation (P 0.01) between marrow involvement before therapy and white blood cell counts (wbc), hemoglobin (hgb), absolute lymphocyte counts, and beta2-microglobulin (beta2-m) but none of these parameters correlated with the lymphoid infiltrate at the end of three or six courses of therapy. more importantly, lymphoid infiltration after three and six courses did not correlate with time to progression (ttp) or overall survival (os). however, patients with >70% marrow involvement before therapy had a significantly shorter TTP (P = 0.02). All 91 patients showed similar results. However, we found reverse correlation between marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01).


Taxonomy and molecular epidemiology of Cryptosporidium and Giardia - a 50 year perspective (1971-2021).
The protozoan parasites Cryptosporidium and Giardia are significant causes of diarrhoea worldwide and are responsible for numerous waterborne and foodborne outbreaks of diseases. Over the last 50 years, the development of improved detection and typing tools has facilitated the expanding range of named species. Currently at least 44 Cryptosporidium spp. and >120 genotypes, and nine Giardia spp., are recognised. Many of these Cryptosporidium genotypes will likely be described as species in the future. The phylogenetic placement of Cryptosporidium at the genus level is still unclear and further research is required to better understand its evolutionary origins. Zoonotic transmission has long been known to play an important role in the epidemiology of cryptosporidiosis and giardiasis, and the development and application of next generation sequencing tools is providing evidence for this. Comparative whole genome sequencing is also providing key information on the genetic mechanisms for host specificity and human infectivity, and will enable One Health management of these zoonotic parasites in the future.


Genome Sequences of Two Strains of Salmonella enterica Serovar Enteritidis Isolated from Shell Eggs.
This report presents the complete genome sequences of two Salmonella enterica serovar Enteritidis strains bearing the pulsed-field gel electrophoresis profile JEGX01.0004, which were isolated from the internal contents of eggs.


The prospective influence of COVID-19 affective risk assessments and intolerance of uncertainty on later dimensions of health anxiety.
The COVID-19 pandemic is likely to increase risk for the development of health anxiety. Given that elevated health anxiety can contribute to maladaptive health behaviors, there is a need to identify individual difference factors that may increase health anxiety risk. This study examined the unique and interactive relations of COVID-19 affective risk assessments (worry about risk for contracting/dying from COVID-19) and intolerance of uncertainty to later health anxiety dimensions. A U.S. community sample of 364 participants completed online self-report measures at a baseline assessment (Time 1) and one month later (Time 2). Time 1 intolerance of uncertainty was uniquely associated with the Time 2 health anxiety dimension of body vigilance. Time 1 affective risk assessments and intolerance of uncertainty were uniquely associated with later perceived likelihood that an illness would be acquired and anticipated negative consequences of an illness. The latter finding was qualified by a significant interaction, such that affective risk assessments were positively associated with anticipated negative consequences of having an illness only among participants with mean and low levels of intolerance of uncertainty. Results speak to the relevance of different risk factors for health anxiety during the COVID-19 pandemic and highlight targets for reducing health anxiety risk.


Quality of life of children during distraction osteogenesis: a comparison between intramedullary magnetic lengthening nails and external fixators.
Distraction osteogenesis is a very demanding process. For decades, external fixation was the only reliable option for gradual deformity correction. Recently, intramedullary magnetic nails have gained popularity. This research aimed to assess the quality of life in children during gradual deformity correction using intramedullary lengthening nails compared to external fixation. Prospective analysis included children who had gradual lower limb deformity correction between 2017 and 2019. Group A included children who had magnetic lengthening nails; patients in group B had external fixation devices. Child health utility 9D (CHU- 9D) and EuroQol 5D youth (EQ- 5D-Y) were used to measure the quality of life at fixed points during the distraction osteogenesis process. The results were used to calculate the utility at each milestone and the overall quality of life adjusted years (QALYs). Thirty-four children were recruited, group A had 16 patients, whilst group B had 18 patients. The average ages were 16.0 years and 14.7 years for groups A and B, respectively. Group A patients reported significantly better utility compared to group B. This was observed during all stages of treatment (P = 0.00016). QALYs were better for group A (0.44) compared to group B (0.34) (P < 0.0001). The quality of life was generally better in group A compared to group B. In most patients, the health utility progressively improved throughout treatment. In the same way, QALYs were better with the lengthening nails compared to external fixators. The magnetic lengthening devices (PRECICE nails) which were used in this research were recently relabelled to restrict their applications in children; this study was conducted before these restrictions.


Transverse sectioning of plastic-embedded immunolabeled cryosections: morphology and permeability to protein A-colloidal gold complexes.
In order to provide data for meaningful interpretation and quantitation of immunogold labeling on cryosections their morphology and permeability to protein A-gold were evaluated: We studied plastic sections of immunogold-labeled ultrathin and semithick cryosections cut perpendicular to the original cryosection plane. Various soluble and insoluble antigens in different specimens (hemoglobin and histone H5 in chicken erythrocytes, tubulin in Leishmania cells, and outer membrane protein OmpA in Escherichia coli) were fixed with glutaraldehyde-formaldehyde, formaldehyde, or periodate-lysine-paraformaldehyde and incubated with specific antibodies and protein A-gold of different sizes. The cryosection surface may be rough or smooth depending both on the sectioned material and on dehydration and drying artifacts or possibly on the cutting process itself. Well-preserved sections are capable of withstanding considerable deformation without showing clefts or cracks. If the sectioned specimen is sufficiently fixed, protein A-gold is not able to enter the IgG-labeled sections significantly but follows surface irregularities. However, gold particles can be detected within visibly damaged sections.


Gadobenate dimeglumine-enhanced liver magnetic resonance imaging: value of hepatobiliary phase for the detection of focal liver lesions.
The objective of the study was to determine the value of addition of hepatobiliary phase to dynamic gadobenate dimeglumine (Gd-BOPTA)-enhanced imaging for the detection of focal liver lesions (nodules with diameter ≤3.0 cm). Routine nonenhanced magnetic resonance images were obtained in 25 patients with focal liver lesions suggested by ultrasonography and/or computed tomography.T1-weighted dynamic gradient-echo images were acquired immediately and 100 minutes after bolus injection of Gd-BOPTA. The number of the lesions detected by T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced, and delayed hepatobiliary-phase imaging was counted, respectively. Contrast-to-noise ratios were measured for all the sequences including delayed hepatobiliary-phase imaging. The signal intensity and morphologic features of liver parenchyma and lesions were recorded and analyzed. There were 7 patients with hepatocellular carcinomas, 6 with hemangiomas, 7 with metastases, and 5 with cholangiocarcinomas. The delayed hepatobiliary-phase imaging showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions. The delayed hepatobiliary-phase imaging was better than diffusion-weighted imaging for the detection of focal liver lesions (P < 0.05). The addition of hepatobiliary-phase imaging to Gd-BOPTA-enhanced dynamic imaging increased the sensitivity and accuracy for the detection of focal hepatic lesions.


A case of hydronephrosis caused by arteriosclerotic compression of the renal pelvis.
We present the case of a 65-year-old woman with vascular compression of the renal pelvis, causing calyectasis. The diagnosis was a subtype of Fraley's syndrome. The cause of compression was concluded to be arteriosclerotic change of both the renal artery and the abdominal aorta.


Towards an optimal perimetric strategy for progression detection in glaucoma: from fixed-space to adaptive inter-test intervals.
The aim was to compare two perimetric strategies for progression detection in glaucoma. Two perimetric strategies for progression detection were compared by means of a thought experiment in a theoretical cohort. In strategy I, visual field testing is performed with fixed-space inter-test intervals at a frequency of two tests per year. In strategy II, the frequency of visual field testing is set to one test per year as long as the fields are apparently unchanged, whereas as soon as progression is suspected, confirmation or falsification is performed within a short time span. Outcome measures were the time delay between the progression event and the diagnosis of definite progression, and the number of visual field tests performed per patient per year. Average time delay between the actual progression event and the final diagnosis of definite progression was 15 months in the case of strategy I and 6 months in the case of strategy II. Maximum time delays were 18 and 12 months respectively. The frequency of visual field testing was 2 tests per patient per year for strategy I and 1.45 tests per patient per year for strategy II. Perimetry in glaucoma can be optimised by postponing the next test in the case of an apparently stable field and accelerating the next test in the case of a suspected progression. This results in an earlier diagnosis, a lower perimetric frequency and a shorter period of uncertainty for the patient.


Magnetic Ionic Liquids in Analytical Microextraction: A Tutorial Review.
Magnetic ionic liquids (MILs) are materials of special interest in analytical chemistry and, particularly, in analytical microextraction. These solvents possess several of the properties derived from their inherent nature of ionic liquids, combined with their magnetism, that permits their manipulation with an external magnetic field. This feature allows for performing typical steps of the microextraction procedure in a simpler manner with the aid of a strong magnet. Although there are several important reviews summarizing the most innovative advances in this field, there is a gap of information, as they do not provide useful details and tips related to the experimental set up of these procedures. This tutorial review fills this gap by providing a guide for the proper handling of MILs, their manipulation with magnets, and their proper hyphenation with the most used analytical techniques. Attention is paid to dispersive liquid-liquid microextraction, stir-bar dispersive liquid microextraction, aqueous biphasic systems, and single-drop microextraction, for being the analytical microextraction techniques mostly employed with MILs. This review also introduces a classification of the MILs employed in analytical microextraction in three classes (denoted as A, B, and C) as a function of the MIL nature (metal-containing anion, metal-containing cation, and radical-containing ion), and discuss about the prospect and future trends regarding new MIL families in microextraction together with new directions expected in these procedures.


A closer association between blood urea nitrogen and the probability of diabetic retinopathy in patients with shorter type 2 diabetes duration.
Blood urea nitrogen (BUN) is an indicator of renal function and catabolic status in human body. Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus (DM) and a serious threat to the vision of diabetic patients. We included 426 type 2 diabetic patients who visited the endocrinology department of Guangdong Provincial People's Hospital and received an ophthalmology consultation from December 2017 to November 2018. The outcome was the probability of DR in participants. Multivariable logistics analysis was used to confirm the relationship between BUN and the probability of DR. And interaction tests were conducted to find the effects of DM duration on their association. A total of 167 of 426 patients with type 2 diabetes had DR, with a probability of 39.20%. After adjusting for potential confounders, a positive association between BUN and the probability of DR (OR = 1.12; 95% CI 1.03-1.21; P = 0.0107). And a test for interaction between DM duration and BUN on the probability of DR was significant (P = 0.0295). We suggested that in patients with type 2 diabetes, BUN was positively associated with the probability of DR and the association was influenced by DM duration.


Non-communicable disease comorbidities in HIV patients: diabetes, hypertension, heart disease, and obstructive sleep apnea as a neglected issue.
The present study evaluates the non-communicable disease (NCD) patterns and related risk factors among people living with HIV (PLWH) in Iran. This national cross-sectional survey study was conducted on 1173 confirmed PLWHs with a mean age of 35.35 (56.82 Over 50 years old, 33.90 Under 50 years old) admitted from 15 different provinces in the country. Logistic regression was used to analyze the association of factors with having at least one NCD comorbidity. From 1173 PLWH, 225(19.18%) participants experienced at least one NCD (15.20% and 38.69% among under- and over-50-year-old patients, respectively). The prevalence of heart disease, hypertension, diabetes, and sleep apnea among all patients was 1.59%, 2.05%, 1.55%, and 10.26%, respectively. The similar prevalence for each NCD among those over 50 years was 10.11%, 15.71%, 9.01%, 25.44%, and 1.01%, 1.12%, 1.04%, and 9.23% among those under 50 years, respectively. The odds of being at risk of at least one NCD stood higher in patients over 50 years (ORadj = 2.93, 95% CI 1.96-4.37), married (ORadj = 2.48, 95% CI 1.41-4.35), divorced or widowed (ORadj = 2.78, 95% CI 1.48-5.20), and obese (ORadj = 3.82, 95% CI 2.46-5.91). According to our findings regarding the prevalence of NCDs among patients under 50 years of age, we recommend that policymakers give greater consideration to this group in the screening and care programs for NCDs since adults and the elderly are both vulnerable to the risk factors for developing NCDs.