Enrichment of omega-3 fatty acids in suckling pigs by maternal dietary fish oil supplementation.
This study was designed to determine whether substituting menhaden fish oil (FO) for lard (LA) in a practical sow diet was a suitable method for enriching newborn pigs with omega-3 polyunsaturated fatty acids (n-3 PUFA). On d 107 of gestation, 18 crossbred sows were randomly allotted to one of three experimental diets, in which FO was substituted for LA at 0, 3.5, and 7% of the diet. On d 1, 7, 14, and 21 after farrowing samples of milk and serum from the sows and pig serum were collected for fatty acid analysis. The content of n-3 PUFA in the serum of sows fed FO increased six-fold over that in serum of LA-fed sows P < .0001). Feeding FO decreased the levels of arachidonic acid in maternal serum by approximately 50% (P < .0001). Similar changes were reflected in the fatty acid profiles of sow's milk. Pig serum n-3 PUFA levels were elevated over 5- and 10-fold within 24 h of birth in those litters born to sows fed 3.5 and 7% fish oil, respectively. Eicosapentaenoic acid levels in pig serum increased linearly (P < .01) during the first 2 wk postnatally in pigs suckling FO-feds sows and accounted for as much as 12% of the total fatty acids present on d 21. In conclusion, we have demonstrated that feeding FO to sows during late gestation and lactation enriches the newborn pig with n-3 PUFA.


Extended mean-field approach for chimera states in random complex networks.
Identical oscillators in the chimera state exhibit a mixture of coherent and incoherent patterns simultaneously. Nonlocal interactions and phase lag are critical factors in forming a chimera state within the Kuramoto model in Euclidean space. Here, we investigate the contributions of nonlocal interactions and phase lag to the formation of the chimera state in random networks. By developing an extended mean-field approximation and using a numerical approach, we find that the emergence of a chimera state in the Erdös-Rényi network is due mainly to degree heterogeneity with nonzero phase lag. For a regularly random network, although all nodes have the same degree, we find that disordered connections may yield the chimera state in the presence of long-range interactions. Furthermore, we show a nontrivial dynamic state in which all the oscillators drift more slowly than a defined frequency due to connectivity disorder at large phase lags beyond the mean-field solutions.


Antidiabetic potential of medicinal plants.
It is the fact that diabetes can't be cured and it has never been reported that someone had recovered totally from diabetes. The rapidly increasing incidence of diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. Moreover, during the past few years some of the new bioactive drugs isolated from plants showed antidiabetic activity with more efficacy than oral hypoglycemic agents used in clinical therapy. The traditional medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus. The present paper reviews natural medicines with their mechanism of action and their pharmacological test results. Many studies have confirmed the benefits of medicinal plants with hypoglycemic effects in the management of diabetes mellitus. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities. WHO has pointed out this prevention of diabetes and its complications is not only a major challenge for the future, but essential if health for all is to attain. Therefore, in recent years, considerable attention has been directed towards identification of plants with antidiabetic ability that may be used for human consumption. Further, it emphasizes strongly in this regard the optional and rational uses of traditional and natural indigenous medicines.


Dose-Dependent Effects of Ranolazine on Reentrant Ventricular Arrhythmias Induced After Subacute Myocardial Infarction in Rabbits.
Ranolazine has been found to prevent ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study aimed to investigate its efficacy on VAs induced several days post-MI. For this purpose, 13 anesthetized rabbits underwent coronary artery ligation. Ten of these animals that survived AMI were reanesthetized 3 to 7 days later for electrophysiologic testing. An endocardial monophasic action potential combination catheter was placed in the right ventricle for simultaneous pacing and recording. Monophasic action potential duration, ventricular effective refractory period (VERP), and VAs induced by programmed stimulation were assessed. Measurements were performed during control pacing, and following an intravenous infusion of either a low-dose ranolazine (2.4 mg/kg, R1) or a higher dose ranolazine (4.8 mg/kg cumulative dose, R2). During control stimulation, 2 animals developed primary ventricular fibrillation (VF), 6 sustained ventricular tachycardia (sVT), and 2 nonsustained VT (nsVT). R1 did not prevent the appearance of VAs in any of the experiments; in contrast, it aggravated nsVT into sVT and complicated sVT termination in 2 of 6 animals. Sustained ventricular tachycardia cycle length and VERP were only slightly decreased after R1 (112 ± 5 vs 110 ± 6 ms and 101 ± 11 vs 98 ± 10 ms, respectively). R2 suppressed inducibility of control nsVT, VF, and sVT in 2 animals. In 4 animals with still inducible sVT, R2 significantly prolonged VT cycle length by 150 ± 23 ms (P < .01), and VERP by 120 ± 7 ms (P < .001) versus control. In conclusion, R2 exerted antiarrhythmic efficacy against subacute-MI VAs, whereas R1 rather aggravated than prevented these arrhythmias. Ventricular effective refractory period prolongation could partially explain the antiarrhythmic action of R2 in this rabbit model.


Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition.
Inflammatory mediators, including acute phase reactants and cytokines, have been reported to be associated with clinical efficacy in patients with melanoma and other cancers receiving immune checkpoint inhibitors (ICI). Analyses of patient sera from three large phase II/III randomized ICI trials, one of which included a chemotherapy arm, were performed to assess whether baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6) or neutrophil/lymphocyte (N/L) ratios were prognostic or predictive. Baseline and on-treatment sera were analyzed by multiplex protein assays from immunotherapy-naïve patients with metastatic melanoma randomized 1:1 on the Checkmate-064 phase II trial of sequential administration of nivolumab followed by ipilimumab or the reverse sequence. Baseline sera, and peripheral blood mononuclear cells using automated cell counting, were analyzed from treatment-naïve patients who were BRAF wild-type and randomly allocated 1:1 to receive nivolumab or dacarbazine on the phase III Checkmate-066 trial, and from treatment-naïve patients allocated 1:1:1 to receive nivolumab, ipilimumab or both ipilimumab and nivolumab on the phase III Checkmate-067 trial. Higher baseline levels of IL-6 and the N/L ratio, and to a lesser degree, CRP were associated with shorter survival in patients receiving ICI or chemotherapy. Increased on-treatment levels of IL-6 in patients on the Checkmate-064 study were also associated with shorter survival. IL-6 levels from patients on Checkmate-064, Checkmate-066 and Checkmate-067 were highly correlated with levels of CRP and the N/L ratio. IL-6, CRP and the N/L ratio are prognostic factors with higher levels associated with shorter overall survival in patients with metastatic melanoma receiving ICI or chemotherapy in large randomized trials. In a multi-variable analysis of the randomized phase III Checkmate-067 study, IL-6 was a significant prognostic factor for survival.


The role of terphenyl-containing carboxylic acid in the oligomerization of aryl vinyl ketone.
The molecular structure of 8-((4''-((1R,4S)-4-butylcyclohexyl)-2'-chloro-[1,1',4',1''-terphenyl]-4-yl)oxy)oct-1-en-3-one (TERPh-VK) and 6-((4''-((1R,4S)-4-butylcyclohexyl)-2'-chloro-[1,1':4',1''-terphenyl]-4-yl)oxy) hexanoic acid (TERPh-COOH) is analyzed by FTIR spectroscopy. Vinyl ketone isolated from solution forms a thermodynamically unstable cis conformation due to probable peculiarities of the crystal structure formation. The heating of this substance above 100 °C results in the cis-trans transformation with the simultaneous opening of the vinyl double bond. The mixing of the above terphenyls in solution followed by the isolation of the solid product results in the formation of the TERPh-VK/TERPH-COOH associated species due to the H-bonding between ketone and carboxylic groups. The thermal transformation of the H-bond associated species resulted in the formation of the oligo (TERPh-VK)/TERPh-COOH associated species.


A Study on the Surface Quality of Selective Laser Melted Cylindrical- and Parallelepipedic-Shaped Inner Structure.
A systematic study was conducted to investigate the distinct mechanisms involved in the formation of the inner surfaces of cylindrical and parallelepipedic-shaped structures. The surface roughness, flatness, and sinking distance were used as key indices to measure the quality of overhanging surfaces, while the surface flatness and roughness were used to evaluate the quality of the side and bottom surfaces of the inner hole. The inner surface morphology was observed using a scanning electron microscope and a white light interferometer. The test results show that the quality of the overhanging surface had a significant impact on the quality of the parallelepipedic-shaped inner hole. In contrast, the cylindrical-shaped inner hole had a shorter but more uniformly distributed overhanging surface, resulting in a different behavior of the overhanging and side surface quality. An improved model of the overhanging surface was established by combining all of the above results and comparing them with the traditional Euler Bernoulli beam model. The factors affecting the quality of the overhanging surface were analyzed, and measures for improving the quality of the overhanging surface during the SLM manufacturing process were proposed.


The kinetics and mechanism of the ferrate(VI) oxidation of hydroxylamines.
Aqueous solutions of potassium ferrate(VI) cleanly and rapidly oxidize hydroxylamine to nitrous oxide, N-methylhydroxylamine to nitrosomethane, N-phenylhydroxylamine to nitrosobenzene, and O-methylhydroxylamine to methanol and nitrogen. The kinetics show first-order behavior with respect to each reactant and a two term component representing acid dependent and independent pathways. A general mechanism involving intermediate formation coupled with a two-electron oxidation is proposed.


Self-sandwich method. An improved immunoperoxidase technic for the detection of small amounts of antigens.
The unlabeled antibody peroxidase-antiperoxidase (PAP) sequence has been widely accepted as the most sensitive method for demonstrating antigens in paraffin sections. However, the results have been unpredictable in routine surgical specimens, with frequent false-negative stains. In order to amplify the staining reactions a self-sandwich method was used. The amplifier (antigen itself) was added after the application of specific antibody. The procedure may be repeated several times before the application of the bridge antiserum followed by PAP complexes. The method was designed to increase the number of antigen-antibody layers without increasing the number of heteroantisera in the system. Specimens derived from routine tonsillectomy were studied semi-quantitatively. Based on the number of positively stained Ig-containing cells in germinal centers, the sensitivity of the self-sandwich method was estimated to be 20 to 50 times that of the PAP method. In addition, extracellular Ig (reticular staining) and surface Ig were also stained positively in the germinal centers and lymphocytic mantles, respectively, but were not demonstrated by the PAP method. The enhancement of the sensitivity was achieved without compromising the specificity.


Crystal structure of ORF12 from Lactococcus lactis phage p2 identifies a tape measure protein chaperone.
We report here the characterization of the nonstructural protein ORF12 of the virulent lactococcal phage p2, which belongs to the Siphoviridae family. ORF12 was produced as a soluble protein, which forms large oligomers (6- to 15-mers) in solution. Using anti-ORF12 antibodies, we have confirmed that ORF12 is not found in the virion structure but is detected in the second half of the lytic cycle, indicating that it is a late-expressed protein. The structure of ORF12, solved by single anomalous diffraction and refined at 2.9-A resolution, revealed a previously unknown fold as well as the presence of a hydrophobic patch at its surface. Furthermore, crystal packing of ORF12 formed long spirals in which a hydrophobic, continuous crevice was identified. This crevice exhibited a repeated motif of aromatic residues, which coincided with the same repeated motif usually found in tape measure protein (TMP), predicted to form helices. A model of a complex between ORF12 and a repeated motif of the TMP of phage p2 (ORF14) was generated, in which the TMP helix fitted exquisitely in the crevice and the aromatic patches of ORF12. We suggest, therefore, that ORF12 might act as a chaperone for TMP hydrophobic repeats, maintaining TMP in solution during the tail assembly of the lactococcal siphophage p2.


Trispecific F(ab')3 derivatives that use cooperative signaling via the TCR/CD3 complex and CD2 to activate and redirect resting cytotoxic T cells.
To investigate whether the retargeting of resting CTL can benefit from cooperative signaling between the TCR/CD3 complex and various accessory molecules, such as CD2, CD4, CD5, and CD8, we have constructed a series of trispecific F(ab')3 derivatives. Each derivative was designed to engage effector T lymphocytes with two Fab' arms, and tumor cells with a single Fab' arm. They were constructed by selective coupling of three mAb Fab' fragments, primarily via their hinge-region sulfhydryl groups, using the cross-linker o-phenylenedimaleimide. En route to the production of trispecific F(ab')3 antibodies a range of bispecific F(ab')2 derivatives was first prepared which could bind simultaneously to two different receptor molecules on T cells. Bispecific derivatives containing specificities for (CD2 (T11(1)) x CD3), (CD3 x CD4), (CD3 x CD8) or two epitopes on CD2, ((T11(1) x (T11(3)), all yielded two to three times the uptake of [3H]thymidine with fresh PBMC to that seen with intact IgG from anti-CD3 (OKT3). The exception to these findings was a bispecific F(ab')2 derivative with specificities for (CD3 x CD5) which caused slightly less proliferation than the control reagent, OKT3 IgG. When these bispecific antibodies were converted into trispecific antibodies (TsAb) by the addition of a Fab' from anti-CD37 they were then all able to retarget resting, unprimed, T cells from fresh PBMC for lysis of CD37+ tumor cells. However, the cytotoxic activity of these reagents fell into two distinct groups: group one, containing (anti-CD3 x anti-CD4 x anti-CD37), (anti-CD3 x anti-CD5 x anti-CD37), and (anti-CD3 x anti-CD8 x anti-CD37), gave minimal lysis and behaved in a similar way to the BsAb, (anti-CD3 x anti-CD37), i.e., no evidence of cooperative signaling for lysis; and group two, containing (anti-T11(1) x anti-CD3 x anti-CD37) and (anti-T11(1) x anti-T11(3) x anti-CD37), which were highly cytotoxic and gave up to 80% specific 51Cr-release. The failure of group one TsAb, in particular (anti-CD3 x anti-CD8 x anti-CD37) which should recruit CD8+ CTL, to give efficient lysis despite having anti-T cell arms that were mitogenic as a bispecific antibody, indicates that the cooperative signaling for proliferation is probably distinct from the signal(s) provided by group two TsAb that activate for both proliferation and lysis.(ABSTRACT TRUNCATED AT 400 WORDS)


The organization and operation of a study of diarrheal disease in Fresno County.
The procedures used in the organization and operation of a special study on diarrheal diseases involving federal, state, and local agencies are outlined. The integration of such a project into a local routine program is discussed and the possible benefits derived by the various agencies are briefly evaluated.


[Sigmund Freud and Herbert Silberer: conjectures on the addressee of a letter by Freukd written in 1922].
This article starts by exposing a number of biographical facts concerning Herbert Silberer, one of the pioneers of the psychoanalytic movement. This information has already been presented in a new edition of selected passages from Silberer's work (Nitzschke, 1988a). The article then goes on to make a critical study of a letter written by Freud in 1922 which was thought up till now to have been addressed to Herbert Silberer. By basing our analysis on the first publication of this letter we have been able to show that it was not addressed to Herbert Silberer, but to his father Victor, thus refuting certain suppositions that are linked to the contents of this letter and according to which Freud was partly responsible for Herbert Silberer's suicide.


Blood Pressure Before Initiation of Maintenance Dialysis and Subsequent Mortality.
Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown. Observational study. 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160mmHg in 10-mmHg increments) and 5 (<60 to ≥90mmHg in 10-mmHg increments) categories, respectively, and as continuous measures. Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access. Mean predialysis SBP and DBP were 141.2±16.1 (SD) and 73.7±10.6mmHg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP<140mmHg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ≥160 (vs 140-<150) mmHg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. Results cannot be inferred to show causality and may not be generalizable to women or the general US population. Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.


Subunit structure and functional properties of the predominant globulin of perilla (Perilla frutescens var. frutescens) seeds.
Approximately 40% of defatted perilla seeds consists of proteins which are primarily composed of globulin (84%). The amino acid profile of perilla proteins demonstrated balanced amounts of all essential amino acids, except for lysine. The molecular mass of the predominant globulin was estimated to be 340 kDa by gel filtration. This globulin was separated into three intermediary subunits (54, 57 and 59 kDa) by SDS-PAGE. It is suggested from these results that the globulin exists as a hexamer. A treatment with 50 mM dithiothreitol enabled the intermediary subunits to be separated into three acidic subunits (31-34 kDa) and four basic subunits (23-25 kDa). It is interesting that this subunit structure is the same as that of sesame α-globulin, despite them coming from different families. Compared to sesame α-globulin, the heat-induced gel of perilla globulin had better water-holding ability, despite it displaying the same degree of gel hardness.


Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA).
The octamer sequence ATGCAAAT is found in the promoters of immunoglobulin (Ig) heavy and light chain genes and in the heavy chain enhancer and is a major determinant of the cell type specific expression of Ig genes in B cells. An apparent paradox is that the same sequence serves as an upstream promoter or enhancer element in a variety of housekeeping genes such as the histone H2B and U snRNA genes. The differential usage of this regulatory sequence motif is thought to be mediated by different species of octamer binding proteins. One species of 100 kd, designated OTF-1, is present in all cell types and may exert its activating function only when it can interact with additional adjacent transcription factors. The lymphoid cell specific octamer binding protein of 60 kd (OTF-2A) specifically stimulates Ig promoters which consist essentially of a TATA-box and an octamer sequence upstream of it. Here we present evidence for yet another B cell specific octamer binding protein of 75 kd (OTF-2B). From several findings, including the absence of OTF-2B (but not OTF-2A) from a lymphocyte line that cannot respond to the IgH enhancer, we propose a role of the novel octamer factor in the long range activation by the IgH enhancer. We have used the proteolytic clipping bandshift assay (PCBA) technique to distinguish the three different forms found in B cells. This analysis indicates that the 75 kd-species OTF-2B is closely related to the 60 kd species OTF-2A.


Experimental studies on the radiation-modifying effect of bleomycin in malignant and normal mouse tissue in vivo.
The interaction between bleomycin (BLM) and radiation was studied in a C3H mammary carcinoma and its surrounding normal skin. In the skin, single and fractionated doses of sequential treatment with BLM (25 mg/kg) 24 hours prior to radiation therapy did not influence the response to irradiation, whereas simultaneous treatment with BLM given 15 minutes before radiation therapy enhanced the reaction to irradiation by a factor of 1.2 or 1.4 following treatment with one fraction or five fractions, respectively. The tumor response to irradiation was not influenced by a single sequential treatment, but five daily fractions of radiation therapy following five daily dose fractions of BLM increased the radiation dose needed to control 50% of the tumors, probably because the tumors continued to grow during the BLM treatment. Simultaneous treatment enhanced the response to irradiation by a factor of 1.2 after both single-dose and fractionated therapy. Based on these data it was concluded that none of the combined treatment schedules were able to produce a better therapeutic effect than radiation therapy alone. Furthermore, mortality due to lung fibrosis in mice treated with BLM indicated the marked toxicity of the drug. This toxicity was most pronounced after fractionated treatment and when radiation therapy and BLM were given simultaneously.


Co-existing pulmonary tuberculosis and bronchogenic carcinoma. A report of 15 cases.
Eighty patients with carcinoma of the lung have been treated at the Nova Scotia Sanatorium since 1940; in 15, coexisting active pulmonary tuberculosis was present. No characteristic clinical or roentgenological findings indicated that the tuberculous individual also had lung cancer. In four cases cancer was not diagnosed until the lung was examined by the pathologist. In the others a considerable interval elapsed before carcinoma was suspected.Only four patients with known cancer were considered suitable for thoracotomy. In three, an attempt at curative resection was made. One survived over seven years before accidental death; one is alive less than one year after operation; the third died as a result of the surgery. Bronchogenic carcinoma should be suspected in every tuberculous patient over the age of 50; diagnostic investigations should include bronchoscopy and cytological studies of bronchial secretion and sputum. Suspicion of carcinoma in any such patient constitutes an indication for early resection of the tuberculous disease.


Overcoming barriers and improving public health nursing practice.
Public health nurses (PHN) are critical to ensuring the health of communities. Absent the most basic information on the PHN workforce in our state, we conducted interviews with 21 PHN and school health nurse (SHN) leaders and an online survey of PHNs and SHNs practicing in Maryland (N = 491). Our study identified an older, very experienced, and well-educated workforce. Both the interviews and survey identified similar barriers: low salaries, recruitment and hiring challenges, limited funding for public health programs, and no opportunities for education or career advancement. Survey participants also identified barriers of inadequate leadership, recognition, and communication including PHNs not being represented at decision-making tables or at the state leadership level. Strategies to promote public health nursing from leaders and survey participants were similar: increasing awareness about what public health and PHNs do and their value; improving advocacy and stakeholder engagement; improving access and availability of services; improving PHN leadership representation at the state level; a improving PHN salaries and benefits including tuition reimbursement. Although results were similar to national studies, comprehensive, granular workforce data is critical to ensure the public health workforce can meet current and emerging public health needs and that public health infrastructure and services are appropriately funded.


Bold move brings hope for children's services.
Employees may not always give or achieve their best but a "one cure fits all" approach will not solve the problem. Knowing how to motivate, value and energise staff is key to successful management and retention. Sharon Crabtree looks at the different factors that can affect staff motivation and explores how to recognize why individual staff may not be achieving or trying to achieve their full potential.


Contamination status and accumulation characteristics of metals and a metalloid in birds on Teuri Island, Hokkaido, Japan.
Teuri Island, Hokkaido in Japan is an important place for seabirds breeding. We measured the concentrations of heavy metals (Hg, Cd, Cr, Co, Ni, Cu, Zn, and Pb) and a metalloid (As) in rhinoceros auklet (Cerorhinca monocerata) (n = 7), thick-billed murre (Uria lomvia) (n = 2), spectacled guillemot (Cepphus carbo) (n = 6), slaty-backed gull (Larus schistisagus) (n = 15), jungle crow (Corvus macrorhynchos) (n = 3), Japanese anchovy (Engraulis japonica) (n = 6) and Atka mackerel (Pleurogrammus azonus) (n = 2). Spectacled guillemot had high As concentrations, with its source being their feeding habitat. Concentration of Hg in kidney of jungle crow was higher than other seabird species at Teuri.


Somatotopic Fascicular Lesions of the Brachial Plexus Demonstrated by High-Resolution Magnetic Resonance Neurography.
The aim of this study was to evaluate whether high-resolution brachial plexus (BP) magnetic resonance neurography (MRN) is capable of (1) distinguishing patients with compressive neuropathy or noncompressive plexopathy from age- and sex-matched controls, (2) discriminating between patients with compressive neuropathy and noncompressive plexopathy, and (3) detecting spatial lesion patterns suggesting somatotopic organization of the BP. Thirty-six patients (50.9 ± 12.7 years) with clinical symptoms, nerve conduction studies, and needle electromyography findings suggestive of brachial plexopathy and 36 control subjects matched for age and sex (50.8 ± 12.6 years) underwent high-resolution MRN of the BP. Lesion determination and localization was performed by 2 blinded neuroradiologists at the anatomical levels of the plexus trunks and cords. By applying defined criteria of structural plexus lesions on high-resolution MRN, all patients were correctly rated as affected, whereas 34 of 36 controls were correctly rated as unaffected by independent and blinded reading from 2 neuroradiologists with overall good to excellent interrater reliability. In all cases, plexopathies with a compressive etiology (n = 12) were correctly distinguished from noncompressive plexopathies with inflammatory origin (n = 24). Pathoanatomical contiguity of lesion from trunk into cord level allowed recognition of distinct somatotopical patterns of fascicular involvement, which correlated closely with the spatial distribution of clinical symptoms and electrophysiological data. Brachial plexus MRN is highly accurate for differentiating patients with symptomatic plexopathy from healthy controls and for distinguishing patients with compressive neuropathy and noncompressive plexopathy. Furthermore, BP MRN revealed evidence for somatotopic organization of the BP. Therefore, as an addition to functional information of electrodiagnostic studies, anatomical information gained by BP MRN may help to improve the efficiency and accuracy of patient care.


[Transition of Psychotropic Drugs in Japanese Pharmacopoeia (JP) (Part 15). Transitions in the Standards and Test Methods of Potassium Bromide in JP I (1886) and JP X VI (2011), and Comparison between the USP and BP].
In mental clinics, bromide agents such as potassium bromide were often once used as therapeutic drugs to treat psychiatric disorders. They were also given as hypnotic, sedative and antiepileptic medicines. However, the appearance of new medicines has resulted in them not being used for these purposes in recent years. Potassium bromide is still continuously listed in today's JP and BP. This suggests that it maintains value as a basic medicine for treating mental disorders in the history of psychotropic medicines. However, regarding the standards and test methods for potassium bromide in the present JP, as a result of a comparison between the USP of the same age, BP and EP, a gap is seen, and this is very regrettable. The exchange of art and scientific information related to medical sciences with foreign countries is becoming more active today. Therefore, scholarly information overseas should be collected and reflected in the standards and test methods for potassium bromide adopted in the JP of Japan. The author believes that the standards and test methods comparable to those at the international level should introduced. On the other hand, potassium bromide was recetnly relisted by USP29 (2006) for the first time in approximately 50 years. Moreover, instrumental analysis was introduced as part of the test methods in BP2013; that is, an epoch-making revision was made in terms of test methods. It is assumed from this that there is a sign of new change regarding the existence of potassium bromide as hypnotic, sedative and antiepileptic medicines, and its utility value. It is believed that the sign of change in view of the utility value and pharmacological evaluation probably arose with the new clinical knowledge that potassium bromide was used to treat a baby seriously ill with myoclony epilepsy, as well as to treat a dog with epilepsy.


Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery.
To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). In patients with pre-CRT serum CEA ≥6 ng/ml, those with "normalized" CEA levels after CRT may have similar DFS to those with "normal" (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.


Size-Selective Exclusion Effects of Liquid Crystalline Tactoids on Nanoparticles: A Separation Method.
Liquid crystalline tactoids are anisotropic microdroplets existing in isotropic phases. We studied the structure and evolution of tactoids in the presence of doping nanoparticles by electron microscopy at the resolution of individual mesogens and observed size-selective exclusion effects of liquid crystalline tactoids on foreign nanoparticles. We applied this principle to the separation of polymer nanospheres, gold nanoparticles, and magnetic nanoparticles by size. These results indicate a new way to size-selectively separate nanoparticles using lyotropic liquid crystals, in which nanoparticles smaller than a threshold size will be selectively transferred from the disordered phase into the ordered phase by tactoids during the phase separation process.


Location detection of key areas in medical images based on Haar-like fusion contour feature learning.
Key area location is an important content of medical image processing and an important detail of auxiliary medical diagnosis. In this paper, a prior knowledge fusion method based on Haar-like feature and contour feature is proposed to locate and detect key areas in medical images. For the image to be processed, six Haar-like features and five contour features are extracted respectively. The improvement of Haar-like feature extraction template better adapts to the complexity of regional structure of medical images. The design of the contour feature extraction process fully reflects the consideration of feature invariance. The two features, together with prior knowledge, are fed into their respective decision makers and final fusers as the basis for determining and locating key regions. The experimental results show that the proposed method has excellent performance in locating key regions of medical images on MRI. When the capacity of the database increases from 10 to 200, the accuracy of locating the key areas of the image to be processed still reaches more than 90%. The proposed method realizes the accurate location of the key areas of medical images, which is of great significance for the auxiliary medical diagnosis.


Successful management of severe respiratory failure combining heliox with noninvasive high-frequency percussive ventilation.
Heliox has been shown to be beneficial in the management of different obstructive pulmonary disorders. High-frequency percussive ventilation has recently been advocated to treat lung injury in children with reduced lung compliance. We report our experience of combining heliox with noninvasive high-frequency percussive ventilation in a 5-yr-old boy with severe acute respiratory failure resulting from advanced cystic fibrosis lung disease. The dramatic improvement allowed stabilization and withholding of endotracheal intubation. We hypothesize that this approach improved gas exchange by enhancing molecular diffusion and by favoring laminar flow throughout the upper and lower airways. Further investigations should study the mechanisms of this noninvasive bimodal therapy.


Klockmannite, CuSe: structure, properties and phase stability from ab initio modeling.
The details of the electronic and crystal structure, the nature of the interatomic bonding and the phase stability of three modifications of klockmannite, CuSe, are analysed using first principles modeling. The hexagonal modification of CuSe is predicted to be less stable than the orthorhombic phase under pressure. The stabilizing force for the orthorhombic phase is identified as the Cu-Cu bond formation between the Cu atoms in the flat hexagonal CuSe layer and in the buckled Cu(2)Se(2) layer. Furthermore, klockmannite is shown to be unstable under compression with respect to the decomposition into umangite, Cu(3)Se(2), and krutaite, CuSe(2) II.


Continuous blood purification in children with severe sepsis.
This study aims to analyse the clinical effects of continuous blood purification (CBP) in children with severe sepsis to form a basis for CBP application in this context. One hundred and twenty children with severe sepsis treated in Binzhou People's Hospital, Shandong, China, from June 2013 to June 2014 were divided into two groups, a treatment and a control group, depending on parental preference. The control group was treated conventionally, and the treatment group underwent CBP in addition to conventional therapy. Cardiovascular and respiratory parameters were measured on admission and after 72 h. This study also assayed interleukin (IL)-8 and tumour necrosis factor (TNF)-α levels, and monitored clinical outcomes and prognosis. The cardiovascular and respiratory parameters of the treatment group improved to a significantly greater extent than did those of the control group (all P less than 0.05). After treatment, the levels of IL-8, IL-6, IL-10, and TNF-α declined in both groups, but more so in the treatment group (all P<0.05). The white blood cell count and C-reactive protein level fell more in the treatment than control group, with statistical significance (both P less than 0.05). CBP remarkably improved the cardiovascular and respiratory functions of children with severe sepsis, probably by eliminating factors mediating inflammation.


SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent.
Superparamagnetic iron oxide (SPIO) acts as a negative contrast agent in magnetic resonance imaging (MRI), and is widely used in clinical applications, including the diagnosis of hepatic diseases. Hepatocyte-targeted magnetic resonance contrast agents (MRCAs) can provide useful information for evaluating hepatic diseases. We prepared targeted magnetic nanostructured lipid carriers (MNLCs) to enhance the hepatocytes targeting efficiency. In vitro characterizations of MNLCs were determined by transmission electron microscopy (TEM). The cytotoxicity assay of the MNLCs was measured by methyl tetrazolium (MTT) method. The uptaken study was measured by confocal microscopy, flow cytometry and MRI in vitro. The enhanced liver-targeting efficiency of MNLCs was measured by fluorescence imaging and MRI in vivo. Gal-NLC-SPIO was prepared successfully. The cytotoxicity assay of the MNLCs demonstrated that the MNLC had relatively low cytotoxicity and high biocompatibility for LO2 cells. More importantly, we confirmed that Gal-NLC-SPIO had greater uptake by LO2 cells than Gal-NLC-SPIO/PEG and free Gal in vitro. A liver distribution study of MNLCs in normal mice demonstrated that the fluorescent signal values to livers of the Gal-NLC-SPIO were significantly stronger than those of NLC-SPIO and Gal-NLC-SPIO/PEG. The liver targeting efficiency of Gal-NLC-SPIO was confirmed both in vitro and in vivo. We successfully developed liver-targeting MNLCs, which showed accurate hepatocytes targeting, and thus have the potential to be a new MRI contrast agent to help the diagnosis of liver diseases.


Mechanisms of solvolyses of acid chlorides and chloroformates. Chloroacetyl and phenylacetyl chloride as similarity models.
[reaction: see text] Rate constants and product selectivities (S = ([ester product]/[acid product]) x ([water]/[alcohol solvent]) are reported for solvolyses of chloroacetyl chloride (3) at -10 degrees C and phenylacetyl chloride (4) at 0 degrees C in ethanol/ and methanol/water mixtures. Additional kinetic data are reported for solvolyses in acetone/water, 2,2,2-trifluoroethanol(TFE)/water, and TFE/ethanol mixtures. Selectivities and solvent effects for 3, including the kinetic solvent isotope effect (KSIE) of 2.18 for methanol, are similar to those for solvolyses of p-nitrobenzoyl chloride (1, Z = NO(2)); rate constants in acetone/water are consistent with a third-order mechanism, and rates and products in ethanol/ and methanol/water mixtures can be explained quantitatively by competing third-order mechanisms in which one molecule of solvent (alcohol or water) acts as a nucleophile and another acts as a general base (an addition/elimination reaction channel). Selectivities increase for 3 as water is added to alcohol. Solvent effects on rate constants for solvolyses of 3 are very similar to those of methyl chloroformate, but acetyl chloride shows a lower KSIE, and a higher sensitivity to solvent-ionizing power, explained by a change to an S(N)2/S(N)1 (ionization) reaction channel. Solvolyses of 4 undergo a change from the addition/elimination channel in ethanol to the ionization channel in aqueous ethanol (<80% v/v alcohol). The reasons for change in reaction channels are discussed in terms of the gas-phase stabilities of acylium ions, calculated using Gaussian 03 (HF/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-311G(d,p) MO theory).


Mixed Dentition Period Follow-up of Primary Unilateral Cleft Nose Deformity Repair.
Recently, there has been an increased acceptance of the primary cleft rhinoplasty providing acceptable outcomes. Nose reconstruction, and specifically cleft nose deformity, should be addressed based on this philosophy. The purpose of this study was to evaluate surgical outcomes during the mixed dentition period after primary surgery to address unilateral cleft lip nose deformity based on the proposed technique. This is a retrospective cohort study. Thirty-two primary complete unilateral cleft lip patients were operated on by a single surgeon using the V-Y-Z cleft rhinoplasty. This method combines a composite V-Y advancement flap with lateral Z-plasty. Data collection was accomplished by evaluation of nasal symmetry through anthropometric measurements performed under general anesthesia during primary cleft palatoplasty and alveolar bone graft. The outcomes were evaluated through anthropometric measurements of the repaired nose during the mixed dentition period of follow-up, and no type of presurgical management was performed for any of the patients. Total nasal symmetry has been observed in 34.37% of patients at 7 years or more and 40.62% at 1-year follow-up. Nonstatistically significant differences were observed during follow-up, and major revision requirement (>3 mm of asymmetry in any of the nose measurements) was observed in 9.37% of patients. The proposed primary cleft rhinoplasty is a good approach to improve nasal appearance in patients with complete unilateral cleft lip and palate.


Toxin production, adherence and protein expression by clinical Aeromonas spp. isolates in broth and human pooled ileostomy fluid.
The physiological behaviour of clinical Aeromonas spp. isolates was compared following culture in a conventional broth and human pooled ileostomy fluid (PIF). Protein expression was markedly affected by the growth medium, with an overall reduction in whole cell proteins in bacteria grown in ileostomy fluid. In addition, novel outer membrane proteins were produced in PIF but not in broth. The majority of A. hydrophila and A. sobria isolates produced toxin in both broth and PIF, whereas no cytotoxin positive A. caviae were found. Toxin titres were at least two doubling dilutions higher in 40% and 21% of A. hydrophila and A. sobria isolates, respectively, following culture in brain heart infusion broth compared with PIF. Bacterial adherence to Vero and A-549 cells was significantly more common in A. hydrophila (53%) and A. sobria (64%) than in A. caviae (15%) (P < 0.01). We observed increased adherence by 6 aeromonas strains previously classified as adherence-positive, but not by 6 non-adherers, in PIF compared with brain heart infusion broth. The influence of growth medium on the expression of potential virulence determinants by Aeromonas spp. provides a rationale for the use of human ileostomy fluid in future in vitro studies, in order to simulate the nutrient conditions found in vivo.


Progressive muscle relaxation increases slow-wave sleep during a daytime nap.
Sleep is critical for health, cognition, and restorative processes, and yet, many experience chronic sleep restriction. Sleep interventions have been designed to enhance overnight sleep quality and physiology. Components of these interventions, like relaxation-based progressive muscle relaxation (PMR), have been studied in isolation and have shown direct effects on sleep architecture, including increasing time in restorative, slow-wave sleep (SWS). These relaxation methods have been understudied in naps, which are effective fatigue countermeasures that reduce deleterious effects of chronic sleep restriction. We hypothesised that PMR should boost SWS in a nap, as compared to an active control. We used a between-subject design in which healthy young adults underwent PMR training or listened to Mozart music (control) prior to a 90-min nap opportunity. We assessed changes in the amount and lateralisation of SWS, as evidence suggests left hemispheric lateralisation may be a proxy for recuperative sleep needs, and changes to state-dependent anxiety and fatigue before and after the nap to assess intervention success. We found PMR participants spent ~10 min more in SWS, equivalent to 125% more time, than the control group, and concomitantly, significantly less time in rapid eye movement sleep. PMR participants also had greater right lateralised slow-wave activity and delta activity compared to the control suggesting a more well-rested brain profile during sleep. Further, pre-sleep anxiety levels predicted nap architecture in the intervention group, suggesting benefits may be impacted by anxiety. The feasibility and accessibility of PMR prior to a nap make this an interesting research avenue to pursue with strong translational application.


Long Standing Eculizumab Treatment without Anticoagulant Therapy in High-Risk Thrombogenic Paroxysmal Nocturnal Hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan disease affecting all hematopoietic cell types. The abnormality of red blood cells in this disease predisposes to intravascular complement-mediated hemolysis. Eculizumab is an orphan drug used to treat this rare disease. Thrombosis is the key cause of death in PNH patients in about 40% to 67% of cases. We report the case of a woman presenting with PNH complicated with serious Budd-Chiari syndrome thrombosis and with a stent inserted in the portal vein. She refused to take any anticoagulant treatment since she commenced eculizumab 4 years before. No thrombotic events happened since that time. This case could add an extra benefit for eculizumab, which could be used as an anti-thromboembolic prophylactic agent in PNH, especially in patients with thrombocytopenia, where the use of anticoagulant agents is extremely hazardous. More randomized studies might establish the use of eculizumab without anticoagulants to avoid serious bleeding that could happen in thrombocytopenic PNH patients.


Survival Differences Between Pediatric Head and Neck Versus Body Melanoma in the Surveillance, Epidemiology, and End Results Program.
To review the demographics, treatment, and survival of pediatric melanoma of the head and neck and to determine if melanoma of the head and neck has worse survival than melanoma of other body sites. Retrospective database review. Pediatric patients from 0 to 21 years in the Surveillance, Epidemiology, and End Results 18 registries database were included from 1975 to 2016 based on a diagnosis of melanoma of the skin using the primary site International Classification of Diseases for Oncology, Third Edition codes from C44.0-C44.9.skin of lip, C44.1-eyelid, C44.2-external ear, C44.3-skin other/unspecified parts of face, C44.4-skin of scalp and neck, C44.5-skin of trunk, C44.6-skin of upper limb and shoulder, C44.7-skin of lower limb and hip, C44.8-overlapping lesion of skin, and C44.9-skin, NOS (not otherwise specified). A total of 4,561 pediatric melanomas of the skin were identified. There were 854 (18.7%) cases of melanoma of the head and neck (MHN) and 3,707 (81.3%) cases of melanoma of the body (MOB). The hazard ratio for MHN versus MOB was 1.6 (95% confidence interval: 1.3-2.1) after accounting for sex, race, and age. Of MHN sites, the hazard ratio for melanoma of the scalp and neck was 2.2 (1.1-4.7). The 2- and 5-year Kaplan-Meier overall survival for MHN were 94.6% and 90.7%, respectively, compared with 96.6% and 94.7%, respectively, for MOB (P < .01). Survival outcomes of pediatric melanoma are notably related to anatomic site. Children with melanoma of the scalp and neck have the worst survival of all sites. Additionally, children who are older/white/male are at greater risk for worse survival outcomes. 3 Laryngoscope, 131:E635-E641, 2021.


Flexible magnifying endoscopy with narrow band imaging for the diagnosis of uterine cervical tumors: A cooperative study among gastrointestinal endoscopists and gynecologists to explore a novel microvascular classification system.
Narrow band imaging with magnifying endoscopy (NBI-ME), which is useful for the assessment of micro-vessels, has excellent diagnostic potential for early gastrointestinal epithelial neoplasia. Conventional diagnostic tools for uterine cervical epithelial tumors are still unsatisfactory. An accurate diagnostic tool for uterine cervical epithelial tumors is required to preserve the reproductive ability of young women with uterine cervical tumors. Flexible NBI-ME was performed in patients with cervical squamous cell lesions that required further examinations based on their Pap smear results (cytology ≥ low-grade squamous intraepithelial lesion) at Kagawa University Hospital between April 2014 and April 2015. NBI-ME results concordant with the punch biopsy sites were compared with the histological results. A retrospective review of the NBI-ME images identified abnormal NBI-ME results regarding micro-vascular patterns. All images were categorized as having abnormal features. NBI-ME revealed the following vascular pattern differences of different stage tumors: Dot-like vessels without irregular arrangements and high density in cervical intraepithelial neoplasia (CIN) CIN1-CIN2; dot-like vessels with irregular arrangements and high density in CIN3-carcinoma in situ; crawling vessels in minimum invasive cancer; and willow branch vessels and new tumor vessels in invasive cancer. NBI-ME may be an effective diagnostic tool for uterine cervical epithelial tumors, which may lead to the establishment of a novel classification system.


An unusual foreign body in nasopharynx.
A 4-week-old baby was brought with history of sudden choking, coughing, difficulty in breathing and cyanosis. Plain X-ray neck showed a large screw along with its nut impacted in the nasopharynx, which was retrieved under general anesthesia.


Stabilizing spiral waves by noninvasive structural perturbations.
We suggest a promising engineering approach to structural perturbation that in principle generates arbitrary additional connections artificially. We show that this structural perturbation method can be applied to stabilize spiral waves noninvasively. Furthermore, the stabilization performance is improved dramatically using proper delay for each additional connection to be created. This structural perturbation method with proper parameters can also be considered as a noninvasive adaptive pinning control that obtains better control performance than the typical constant pinning control. Remarkably, we numerically illustrate that a few additional connections (i.e., small structural perturbation) may result in stabilization of spiral waves. All methods suggested are motivated and illustrated with a FitzHugh-Nagumo model.


Cyclosporine pharmacokinetics and variability from a microemulsion formulation--a multicenter investigation in kidney transplant patients.
The steady-state pharmacokinetics and tolerability of a microemulsion formulation of cyclosporine (Sandimmune Neoral) were compared with the commercial formulation (Sandimmune) in 55 clinically stable renal allograft recipients. In study period I (2 weeks' duration), patients entered the study on a stable, individualized twice-daily dosage regimen of the commercial formulation. In period II (2 weeks), they were changed over to the microemulsion formulation at the same dose as at study entry. In period III (2 weeks), dose titration was subsequently allowed if necessary to provide comparable steady-state trough concentrations as at study entry. The commercial formulation was reinstituted during period IV (2 weeks). Safety and tolerability were assessed at weekly clinic visits, and the steady-state pharmacokinetics of cyclosporine in whole blood were characterized at the end of each study period. A milligram-to-milligram dose conversion was adequate when making the initial change between formulations in order to maintain steady-state trough concentrations in the target therapeutic range. Concomitant with this conversion, the steady-state peak concentration and area under the curve increased on average by 59% and 30%, respectively, due to absorption-related differences between the formulations. These increases were not associated with an increase in adverse experiences or changes in blood pressure or clinical laboratory parameters over the first four weeks after the change-over. Trough concentrations were more stable and were more strongly correlated with systemic exposure (area under the curve) during treatment with the microemulsion formulation. Intraindividual coefficients of variation in steady-state peak concentration, time to attain the peak, area under the curve, and percent peak-trough fluctuation ranged from 18% to 74% from the commercial formulation. Variability from the microemulsion formulation was significantly less, ranging from 10% to 22%.


Jump-starting kinesin.
When it is not actively transporting cargo, conventional Kinesin-1 is present in the cytoplasm in a folded conformation that cannot interact effectively with microtubules (MTs). Two important and largely unexplored aspects of kinesin regulation are how it is converted to an active species when bound to cargo and the related issue of how kinesin discriminates among its many potential cargo molecules. Blasius et al. (see p. 11 of this issue) report that either binding of the cargo linker c-Jun N-terminal kinase-interacting protein 1 (JIP1) to the light chains (LCs) or binding of fasciculation and elongation protein zeta1 (FEZ1) to the heavy chains (HCs) is insufficient for activation but that activation occurs when both are present simultaneously. A related paper by Cai et al. (see p. 51 of this issue) provides structural insight into the conformation of the folded state in the cell obtained by fluorescence resonance energy transfer analysis.


Density of lean body mass is greater in blacks than in whites.
Previous studies have reported that Blacks have 10-20% more bone mineral than Whites of the same height. Theoretically, this should mean that the lean body mass of Blacks is denser than that of Whites, such that formulas for calculating lean body mass from density in Whites will overestimate the lean body mass (and thus underestimate fatness) in Blacks. To determine if the lean body mass of Blacks is indeed denser than that of Whites, we measured density, total body water, and anthropometric dimensions in 19 white and 15 black male college students. The black and white cohorts were nearly identical in height, weight, and total body water. Among the Whites there was no significant difference between the observed density and that predicted from anthropometry, nor were there any significant differences between the dimensions of body composition calculated from total body water and from observed density. Among the Blacks, however, the observed density was significantly greater than that predicted from anthropometry, and the lean body mass calculated from observed density was significantly greater than that calculated from total body water. These results are consistent with the hypothesis that the lean body mass of the Blacks is denser than that of the Whites. Separate formulas should therefore be used for converting density to body composition. Based on our data, the correct formula for Blacks is: %fat = 100 X [(4.374/density) - 3.928]. This formula indicates a lean body density of 1.113 g/cm3 in Blacks compared with 1.100 in Whites.


[Spontaneous pneumothorax in young women: possible lymphangioleiomyomatosis].
(Recurrent) pneumothorax developed spontaneously in three women aged 33, 35 and 36 years, two of whom were pregnant. Morbid-anatomical examination of lung biopsy samples in two of them revealed proliferation of smooth muscle cells which through infiltration of pleura, septa, and alveoli had led to loss of pulmonary parenchyma and formation of cystic lesions; the cystic lesions were visible in a CT scan in all three patients. The diagnosis in 2 patients was 'lymphangioleiomyomatosis'; the third patient had anomalies compatible with lymphangioleiomyomatosis, but these were interpreted as tuberous sclerosis because of the presence of renal angiomyolipomas. This disorder occurs exclusively in women in the reproductive age. Treatment consisted in drainage of the pneumothorax, pleurodesis and pleurectomy, with administration of medroxy-progesterone. One year later, the pneumothorax had not recurred.


Multiple literacies: Linking the research on bilingualism and biliteracies to the practical.
The present article addresses the fundamental developmental differences between monolingualism and bilingualism, as outlined in the literature. It takes into account research using qualitative and quantitative methodologies and reviews the advantages and possible disadvantages of bilingualism in preschool children. It then moves on to biliteracies in early childhood education. The questions addressed are: Will the early learning of a second language delay a child's language development? What effect does bilingualism have on the development of phonemic awareness, and does that have an impact on reading development? Do bilingual children have an advantage over monolingual children? What happens when a child with language impairment is called upon to develop two languages? What are some challenges regarding the acquisition of biliteracies? The present article concludes with recommendations for physicians who counsel bilingual families regarding early childhood literacy promotion and development.


Antimelanogenic Effects of Picrionoside A Isolated from the Leaves of Korean Ginseng.
This study was initiated to isolate active metabolites from the leaves of Panax ginseng. Among them, picrionoside A, a megastigmane glucoside, was isolated from the leaves of P. ginseng C. A. MAYER and its chemical structure was determined based on spectroscopic methods, including FAB-MS, one-dimensional (1D)-NMR, 2D-NMR, and IR spectroscopy. Picrionoside A from P. ginseng has not been investigated previously, and its biological or pharmaceutical activities have not been reported elsewhere. The IC50 value of mushroom tyrosinase-inhibitory activity of picrionoside A was 9.8 µM, and the rate of inhibition of synthesized melanin content in melan-a cells was 17.1% at a concentration of 80 µM without cytotoxicity. Furthermore, picrionoside A dramatically reduced body pigmentation in the zebrafish model. Taken together, the results suggest that picrionoside A isolated from the leaves of P. ginseng may be an effective skin-whitening agent that could be a potent candidate material in the cosmetic industry.


Identification and characterization of novel long-term metabolites of oxymesterone and mesterolone in human urine by application of selected reaction monitoring GC-CI-MS/MS.
The search for metabolites with longer detection times remains an important task in, for example, toxicology and doping control. The impact of these long-term metabolites is highlighted by the high number of positive cases after reanalysis of samples that were stored for several years, e.g. samples of previous Olympic Games. A substantial number of previously alleged negative samples have now been declared positive due to the detection of various long-term steroid metabolites the existence of which was unknown during the Olympic Games of 2008 and 2012. In this work, the metabolism of oxymesterone and mesterolone, two anabolic androgenic steroids (AAS), was investigated by application of a selected reaction monitoring gas chromatography-chemical ionization-triple quadrupole mass spectrometry (GC-CI-MS/MS) protocol for metabolite detection and identification. Correlations between AAS structure and GC-CI-MS/MS fragmentation behaviour enabled the search for previously unknown but expected AAS metabolites by selection of theoretical transitions for expected metabolites. Use of different hydrolysis protocols allowed for evaluation of the detection window of both phase I and phase II metabolites. For oxymesterone, a new metabolite, 18-nor-17β-hydroxymethyl-17α-methyl-4-hydroxy-androst-4,13-diene-3-one, was identified. It was detectable up to 46 days by using GC-CI-MS/MS, whereas with a traditional screening (detection of metabolite 17-epioxymesterone with electron ionization GC-MS/MS) oxymesterone administration was only detectable for 3.5 days. A new metabolite was also found for mesterolone. It was identified as 1α-methyl-5α-androstan-3,6,16-triol-17-one and its sulfate form after hydrolysis with Helix pomatia resulted in a prolonged detection time (up to 15 days) for mesterolone abuse. Copyright © 2017 John Wiley & Sons, Ltd.


Urgent surgical reperfusion in acute evolving myocardial infarction. A randomized controlled study.
To assess the benefit of immediate surgical reperfusion over conventional medical treatment during the first acute evolving transmural myocardial infarction, 68 patients presenting within 4 hours of onset of chest pain were randomized into a medical group and a surgical group. Both groups were comparable for age, sex, coronary risk factors, location of infarct, and coronary anatomy. Radionuclide global ejection fraction at 48 hours after admission was 45 +/- 15% for the medical group versus 50 +/- 15% for the surgical group; at 3 months, ejection fraction values were 51 +/- 13% and 51 +/- 13%, respectively (p = NS). The average radionuclide wall-motion scores (normal, 3) at 3 months were 2 +/- 0.6 for the medical group and 2 +/- 0.7 for the surgical group. There were three (8.8%) early and four (11.7%) late deaths in the medical group and only one (2.9%) early death in the surgical group. Urgent surgical reperfusion in acute evolving myocardial infarction is a safe and effective procedure that appears to reduce early and late mortality but does not appear to improve left ventricular function.


[Effects of kinesthetic mobilization in comparison with standard mobilization on respiratory function after coronary artery bypass and other relevant factors].
Presently no relevant nursing data exist in Germany on the effect of mobilization according to kinaesthetic principles on the physiological system, on locomotion and the sensory system. The effect of two different versions of mobilization was measured in a unicentric, open, randomized study with two parallel groups from December 1999 to October 2000 in the intermediate ICU for patients after heart surgery at Ulm University Hospital. The aim was, to show superiority of kinaesthetic mobilization, compared to empirically developed standard mobilization on patients after aortal coronary bypass surgery, with reference to respiratory function. The two protocols of mobilization were carefully coordinated with precise plans of action and timing. A total of 104 subjects were randomized to the two groups. In the kinaesthetic mobilization group (n = 52) median age was 67.5 years, ten (19.2%) were female and 42 (80.8%) were male. In the standard mobilization group (n = 52) median age was 69 years, eight (15.4%) were female and 44 (84.6%) were male. The main outcome variable was the respiratory minute volume 30 minutes after the second mobilization minus the respiratory minute volume prior to the second mobilization. The median change in respiratory minute volume was 0.4 ltr/min. (-5.1 to 3) in the group with kinaesthetic mobilization and median 0.3 ltr/min (-6.0 to +9.1) in the standard mobilization group. Superiority of kinaesthetic mobilization compared to standard mobilization could not be proven (p = 0.38). Also in the secondary outcome variables the kinaesthetic mobilization showed no superiority over standard mobilization. The respiratory minute volume data within points of measure show that subjects in the kinaesthetic group have less extreme results (> 12 ltr.). In the area < 5 ltr. there is a similar tendency. This may point out that regulation between movement of body, respiration and circulatory system occurs more continuous in kinaesthetic mobilization than the standard mobilization. A similar tendency was seen in the secondary outcomes variables. Subjectively nurses noted that kinaesthetic mobilization was less strenuous than standard mobilization, even though subjects in the kinaesthetic group showed more mobility restriction (37%) than in the standard group (15%). From before to after the first mobilization the percentage of subjects needing less pain medication was higher in the kinaesthetic group (35%), compared to the standard group (19%). There were no serious adverse events in either group. The concept of kinaesthetic mobilization showed no negative effect on subjects compared to empirically developed standard mobilization. There was no diagnosis of pneumonia and none of instabile sternum on any of the subjects in this study. Also, there was no negative effect on the sternum due to the light support arms gave to sitting up and rotating movements in the area of thorax and pelvis on subjects in the kinaesthetic group. The subjects early trust in their own varied movement and the possible effects of kinaesthetic mobilization in later phases of recuperation was not explored in this study.


Ultra Sensitive Label-Free Detection of Biomolecules Using Vertically Extended Drain Double Gate Si₀.₅Ge₀.₅ Source Tunnel FET.
This work reports a vertically extended drain double gate Si0.5Ge0.5 source tunnel FET for the biomolecules detection using its electrical properties modulation in presence of biomolecules like cell, DNA, protein, etc. The reported biosensor has a dual source of Si0.5Ge0.5 and two cavities above each source-channel interface for the immobilization of biomolecules. This immobilization modulates the screening/tunneling length and energy range available for tunneling due to the dielectric constant and charge density variations of the biomolecules. The dual cavity structure increases the control of biomolecules on the source to channel tunneling probability and thus realizes an increased control on electrical performance parameters of the biosensor enabling it to have a higher sensitivity towards the biomolecules. Further, the cavity length of the reported biosensor is kept as 45 nm making it suitable for large sized biomolecules and polymers detection also. Our study demonstrates that the reported biosensor structure is resilient towards the process variations and temperature effects. Moreover, the effect of dielectric modulation and charge density modulation has also been analyzed in terms of the variation in the drive current, ON state current, threshold voltage, transconductance, and sub-threshold slope (SS). The sensitivity of the reported biosensor is also compared with the existing biosensors and it is found to be highly sensitive.


Create, run, share, publish, and reference your LC-MS, FIA-MS, GC-MS, and NMR data analysis workflows with the Workflow4Metabolomics 3.0 Galaxy online infrastructure for metabolomics.
Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the multiplicity of bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M; http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows.


Public Medical Preparedness at the "Swiss Wrestling and Alpine Games 2013": Descriptive Analysis of 1,533 Patients Treated at the Largest 3-Day Sporting Event in Switzerland.
Introduction. Medical preparedness at mass gatherings is challenging, as little is known about the optimal planning. Most studies and case reports are based on mass casualty incidents, so the results cannot be extrapolated to mass gatherings. Aim of this study was to evaluate the preclinical medical structure and the frequency of specific injuries and medical emergencies during the event. Methods. Retrospective analysis of a prospectively collected database. Three on-site medical assistance points were set up, completed by mobile teams, and coordinated by an on-site operational management team. Medical staff requirements were calculated using Maurer's formula. Results. A total of 1,533 patients were treated during the three-day event. Overall, the medical usage rate (MUR; patients per 10,000 visitors) was 51.1. A total of 58 patients (3.8%) required a hospital transfer. In 1,063 cases (69.3%) a diagnosis was documented. Of these, 503 patients (47.3%) suffered from hymenoptera stings; the two most common non-trauma-related diagnoses were alcohol/drug intoxication (4.1%) and gastrointestinal diseases (4.0%). Conclusion. Overall, the on-site medical care worked well. However, a high frequency of hymenoptera stings occurred, resulting in a shortage of antihistamine medication. Moreover, more than half of the patients were managed at the second largest medical assistance point. Prospective and critical evaluation of medical care at mass gatherings is crucial in order to optimize on-site medical preparedness at future events.


THE RATE AND EFFECTS DISTRIBUTION OF VIABILITY MUTATION IN DROSOPHILA: MINIMUM DISTANCE ESTIMATION.
The empirical distribution of the mean viability of mutation accumulation lines, obtained from three published experiments, was analyzed using minimum-distance estimation. In two cases (Mukai et al. 1972; Ohnishi 1977), mutations were allowed to accumulate in copies of chromosome II protected from natural selection and recombination. In the other one (Fernández and López-Fanjul 1996), they accumulated in inbred lines derived from an isogenic stock. In contrast with currently accepted hypotheses, we consistently estimated low (about 0.01) genomic viability mutation rates, λ, and a small kurtosis of the distribution of mutational effects on viability (a) in the three datasets. Minimum-distance estimates of the per-generation mean viability change due to mutation (λE[a]) were also obtained. These were very similar for both chromosomal datasets, their absolute values being about five times smaller than estimates obtained from the observed change in mean viability during the mutation process. It must be noted that, in both experiments, viability was measured relative to the Cy chromosome of a Cy/Pm stock. Thus, an unnoticed viability increase in this Cy chromosome may have resulted in overestimation of the mean viability reduction in the lines. In parallel, minimum-distance estimation of λE(a) from inbred lines data (where the selective pressure during the accumulation process was larger) was even somewhat smaller, in absolute value, and very close to the estimate obtained by comparing the mean viability of the lines with that of the control isogenic line. The evolutionary importance of these results, as well as their relevance to the solution of the mutational load paradox, is discussed.


Bioavailable and free 25-hydroxyvitamin D and vitamin D binding protein in polycystic ovary syndrome: Relationships with obesity and insulin resistance.
Polycystic ovary syndrome (PCOS) is a common condition characterised by both reproductive and metabolic features (obesity, insulin resistance, diabetes risk). Some evidence suggests that women with PCOS have lower vitamin D levels compared to healthy controls. Vitamin D binding protein (DBP) is the main carrier of vitamin D in circulation and plays an important role in regulating vitamin D concentration and bioavailability for target tissues. To our knowledge, no previous studies have examined DBP, bioavailable and free 25-hydroxyvitamin D (25(OH)D) in women with PCOS. The primary aim of this study was to compare DBP, bioavailable and free 25(OH)D concentrations in women with PCOS and controls. The secondary aim was to investigate relationships between DBP, bioavailable and free 25(OH)D and metabolic features (anthropometric measures, insulin resistance, and lipid profile). In a cross sectional study using bio-banked samples, we measured 25(OH)D, DBP and albumin. Bioavailable and free 25(OH)D were calculated using previously validated formula. BMI, body composition (dual X-ray absorptiometry, DXA), insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR)) and glucose infusion rate (GIR) from hyperinsulinaemic euglycaemic clamp and serum lipids (ELISA) were also measured in a physically and biochemically well-characterised cohort of women with and without PCOS. We studied 90 women with PCOS and 59 controls aged 18-48 years. DBP concentrations were lower in PCOS compared to controls (median [IQR]: 443.40 [314.4] vs 482.4 [156.8] μg/ml, p=0.02). No significant differences were found in bioavailable or free 25(OH)D concentrations between groups. DBP was not associated with BMI, percent body fat or markers of insulin resistance (all p>0.2). High-density lipoprotein (HDL) was the main determinant of DBP in the overall cohort (β=-0.12, p=0.02), after adjusting for covariates including PCOS/control status, age, BMI, total 25(OH)D and HOMA-IR. In PCOS, total and free 25(OH)D were related to markers of insulin resistance and lipids. Only the associations between free 25(OH)D and triglycerides (p=0.02), and HDL (p=0.03) remained significant after adjusting for age and BMI. In conclusion, women with PCOS had lower DBP, but similar bioavailable or free 25(OH)D concentrations compared to controls, independent of BMI and age. DBP was not associated with insulin resistance or BMI in PCOS. Further studies are needed to investigate the pathophysiology and clinical implications of reduced DBP in PCOS.


Size Matters: From Two-Dimensional AuI -TlI Metallopolymers to Molecular Complexes by Simple Variation of the Steric Demand.
Bis(acetylido) aurates(I) and thallium(I) trifluoromethylsulfonates were used to synthesize AuI -TlI metallopolymers, displaying novel and unusual structural motifs of the metal-metal backbones in the solid state: a discrete molecular cluster, 1D chains of interconnected dimers, tetramers, or dodecamers of Au-Tl units, and a 2D-plane network, consisting of alternating edge-linked (AuTl)6 and (AuTl)4 cycles. The formation of the different architectures was primarily controlled by the steric demand of the acetylide-substituent groups. Thus, the bulkiest 2,6-diisopropylphenyl derivative yielded a molecular cluster [Tl2 Au3 ]. Most compounds showed bright visible photoluminescence with quantum yields of up to 25 % at ambient temperature. The color of the emitted light significantly differs with the network structure. Furthermore, theoretical studies of singlet excitations in the molecular cluster, as well as NMR and mass-spectrometric investigations of the fragmentation of the metallopolymers in solution are described in detail.


Reevaluation of the effects of alcohol consumption on rat liver microtubules: effects of feeding status.
The ability of total, free and microtubule-derived tubulins to bind colchicine was studied (using 4 different methods) in the liver of 12 male rat littermates pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate and kept in the fed state up to the time of sacrifice. In the alcohol fed rats, we found a reproducible decrease in microtubule-derived tubulin and in the percentage of total tubulin present in the polymerized form. This was due to an alteration of the microtubular protein rather than to inhibitory factors of the liver supernatants. An equal group of pair-fed rats was tested after a 24-hour fast. Fasting decreased microtubule-derived tubulin and abolished the inhibitory effect of ethanol, probably by decreasing the rate of ethanol oxidation.


A comparison of effects of fixed and tailored cardiopulmonary bypass flowrates on renal function.
Cardiopulmonary bypass may result in renal impairment but there is little investigative data on the effect of differing flowrates on postoperative renal function. One hundred and twenty-two patients presenting for cardiac surgery were randomly assigned to receive either a fixed CPB flow of 2.4 l.m-2 or a bypass flow tailored to maintain a venous return oxygen saturation of 75-80%. Vasoactive drugs were given to maintain a perfusion pressure of 50 to 80 mmHg. Patients were assessed by serum creatinine, creatinine clearance, arterial blood gases, serum lactates and electrolytes. The results show an overall decline in postoperative renal function compared with preoperative levels, with no significant differences between the two groups.


Behavior of Intermetallic Compounds of Al-Ti Composite Manufactured by Spark Plasma Sintering.
In this research, we successfully fabricate high-hardness and lightweight Al-Ti composites. Al-Ti composites powders with three compositions (Al-20, 50, and 80 vol.% Ti) are mixed using ball milling and subsequently subjected to spark plasma sintering (SPS). The microstructures and phases of the Al-Ti composites are characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, and field emission-electron probe microanalysis (FE-EPMA). These tests confirm the presence of several intermetallic compounds (ICs) (Al₃Ti, Al₅Ti₂, Al11Ti₅) in the composites, and we are able to confirm that these ICs are produced by the reaction of Al and Ti during the SPS process. Furthermore, thermogravimetric-differential thermal analysis (TG-DTA) is used to analyze the formation behavior of the ICs. In addition, the mechanical properties of the composites are measured using their Vickers hardness and it is observed that the Al-80 vol.% Ti composite exhibits the highest hardness. Consequently, it is assumed that SPS is suitable for fabricating Al-Ti composites which represent the next-generation materials to be used in various industrial fields as high-hardness and lightweight materials.


[Complications after implantation of anterior chamber lenses. An analysis of 4,100 explanted intraocular lenses].
In this study we analyzed the incidence and types of complications seen after cataract surgery and implantation of anterior chamber intraocular lenses (AS-IOLs). This report is based on a review of 4104 explanted AC-IOLs that were submitted to the Center for IOL Research over the past 10 years. The results from pathological examinations were correlated with clinical information. Of the 4104 IOLs, 50% were closed-loop designs (n = 2095/4104), and 22% were open-loop lenses (919/4104). The IOLs most frequently explanted were the closed loop designs Leiske (n = 847) and Stableflex (n = 808). The most important reason for explantation was corneal pathology. Closed-loop IOLs had a much higher complication rate than open-loop lenses. Flexible open-loop AC-IOLs showed the highest explantation rate during the first postoperative year due to surgical problems. The complication rate of closed-loop AC-IOLs increased with implant duration and were responsible for 80% of the corneal pathology. Flexible open-loop AC-IOLs can be an alternative for secondary or exchange implantation. Furthermore, they could also be a viable alternative for cataract surgery in developing countries in order to help catch up with the overwhelming backlog of cases that exist there.


The control of guineaworm with abate: a trial in a village of North-West Ghana.
In the village of Gbegru guineaworm infection is contracted by drinking the water of a man-made pond during the dry season. The lethal effect on the vector cyclops of each application of Abate to a concentration of 1 mg/litre lasted 5-7 weeks and was clearly reflected in the following year's incidence of guineaworm cases. This indicates that Abate is potentially useful in the chemical control of guineaworm infection.


Using the new OASIS-based reports in OBQI.
OASIS-derived outcome reports first became available to home care agencies in February 2002 and depicted the agency's current (observed) outcome achievement rate as compared to a reference (predicted) rate on 41 separate outcomes. New three-bar reports are now available that allow agencies to evaluate their current outcome rates against their previous year's rates and a reference rate. This article compares the newly-available three-bar reports with the prior two-bar reports, including information provided in those reports in the OBQI process.


Sub-cycle pulse revealed with carrier-envelope phase control of soliton self-compression in anti-resonant hollow-core fiber.
The influence of the carrier-envelope phase (CEP) of a pump pulse on the multioctave supercontinuum (SC) generation in a gas-filled anti-resonant hollow-core fiber (AR HCF) by soliton self-compression (SSC) has been explored. We have shown an octave-wide third harmonic generation (THG) in the visible-to-near-infrared range during the pulse compression down to a sub-cycle duration. The CEP of a multi-cycle pump pulse provides control of interference between the third harmonic (TH) and the SC that indicates the coherent synthesis of a sub-cycle pulse with a duration of about 0.4 optical cycles and a peak power of more than 2 GW at the fiber output.


The severity of positional mitral regurgitation during off-pump coronary artery bypass grafting.
The aims of this study were to elucidate the incidence of mitral regurgitation during off-pump coronary artery bypass (OPCAB) surgery to evaluate the relationship of the changes with ventricular function and possible mitral valve regurgitation caused by positioning. Included in the study were 60 consecutive patients who underwent CAB grafting on the beating heart. We monitored several hemodynamic variables (systolic arterial pressure, mean arterial pressure, right atrial pressure, pulmonary capillary wedge pressure, and heart rate) at baseline and after each anastomosis and used transesophageal echocardiography (TEE) routinely after sternotomy, during each anastomosis, and after completion of the operation. Valvular functions, ejection fraction, and wall motion systolic index were recorded during each TEE evaluation. All of the patients underwent complete revascularization. We performed 132 consecutive OPCAB anastomoses in 60 patients (60 left anterior descending artery [LAD], 20 right coronary artery [RCA], 45 left circumflex coronary artery [LCX], and 7 diagonal artery grafts). During LCX anastomosis, 38 (84.4%) of 45 patients developed moderate mitral regurgitation. The wall motion score index (WMSI) significantly increased during CX grafting, as was demonstrated by higher WMSI values than for the RCA, diagonal, and LAD grafts. The ejection fraction was decreased significantly during CX and RCA anastomoses compared with baseline levels. The hemodynamic changes were in accord with these findings. The greatest hemodynamic compromise was seen during CX anastomosis. Positional mitral regurgitation occurs frequently and is a major contributor to hemodynamic instability during posterior- and lateral-wall revascularization during the OPCAB procedure.


Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby.
Ibuprofen is preferred to indomethacin for treatment of a significant patent ductus arteriosus (PDA) in preterm babies despite indomethacin being associated with a lower risk of intraventricular haemorrhage. This difference is thought to relate to the discrepant effects of each medication on cerebral oxygen kinetics yet the effect of ibuprofen on cerebral perfusion is uncertain. Forty-eight babies < 30 weeks with a significant PDA, defined by echocardiography, were randomly assigned to either indomethacin or ibuprofen (n = 24 per group) and stratified by gestation and chronologic age. Cerebral blood flow [total internal carotid blood flow (TICF)] and oxygen physiology [oxygen delivery (modCerbDO2) and consumption (modCerbVO2)] were measured using cranial Doppler ultrasound and near-infrared spectroscopy, and cerebral oxygen extraction (cFTOE) calculated, immediately before and following administration. Temporal and treatment related changes were analysed. A fixed effect of time was seen for TICF (p = 0.03) and therefore modCerbDO2 (p = 0.046) and cFTOE (p = 0.04) for indomethacin alone. In the indomethacin group, TICF and modCerbDO2 fell from baseline to 5 and 30 min respectively (TICF p < 0.01, cDO2 p = 0.01) before increasing from 5 min to 24 h (p < 0.01) and 30 min and 24 h (p < 0.01) timepoints. cFTOE peaked at 30 min (p = 0.02) returning to baseline at 24 h. There was a parallel increase in arterial lactate. Indomethacin significantly reduces cerebral blood flow soon after administration, resulting in a parallel increase in oxygen extraction and arterial lactate. This implies that the balance of oxygen kinetics at the time of treatment may be critical in very preterm babies with significant PDA.


Diabetic ketoacidosis and cerebral edema.
Cerebral edema is the leading cause of death in children presenting in diabetic ketoacidosis and occurs in 0.2 to 1% of cases. The osmolar gradient caused by the high blood glucose results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space and contraction of cell volume. Correction with insulin and intravenous fluids can result in a rapid reduction in effective osmolarity, reversal of the fluid shift and the development of cerebral edema. The goals for treatment should be a combination of intravenous fluid and insulin that results in a gradual reduction of the effective osmolarity over a 36- to 48-hour period, thereby avoiding rapid expansion of the ICF compartment and brain swelling.


Seasonal prevalence of Escherichia coli O157:H7 in beef cattle feces.
Cattle are an asymptomatic reservoir of Escherichia coli O157:H7, but the bacterial colonization and shedding patterns are poorly understood. The prevalence and shedding of this human pathogen have been reported to be seasonal with rates typically increasing during warm months. The objectives of this study were (i) to assess the prevalence of E. coli O157:H7 in feces of feedlot cattle in Kansas during summer, fall, and winter months, and (ii) to characterize E. coli O157:H7 by screening for virulence factors. Of 891 fecal samples collected, 82 (9.2%) were positive for E. coli O157:H7. No significant differences in prevalence were detected among summer, fall, and winter months. The highest monthly prevalence (18.1%) was detected in February. All tested isolates were positive for stx2 (Shiga toxin 2) and eaeA (intimin) genes; 14 isolates (12.8%) also carried stx1. Our results indicate the prevalence of E. coli O157:H7 in beef cattle feces is not necessarily season dependent.


Functionalization of boron diiminates with unique optical properties: multicolor tuning of crystallization-induced emission and introduction into the main chain of conjugated polymers.
In this article, we report the unique optical characteristics of boron diiminates in the solid states. We synthesized the boron diiminates exhibiting aggregation-induced emission (AIE). From the series of optical measurements, it was revealed that the optical properties in the solid state should be originated from the suppression of the molecular motions of the boron diiminate units. The emission colors were modulated by the substitution effects (λ(PL,crystal) = 448-602 nm, λ(PL,amorphous) = 478-645 nm). Strong phosphorescence was observed from some boron diiminates deriving from the effects of two imine groups. Notably, we found some of boron diiminates showed crystallization-induced emission (CIE) properties derived from the packing differences from crystalline to amorphous states. The 15-fold emission enhancement was observed by the crystallization (Φ(PL,crystal) = 0.59, Φ(PL,amorphous) = 0.04). Next, we conjugated boron diiminates with fluorene. The synthesized polymers showed good solubility in the common solvents, film formability, and thermal stability. In addition, because of the expansion of main-chain conjugation, the peak shifts to longer wavelength regions were observed in the absorption/emission spectra of the polymers comparing to those of the corresponding boron diiminate monomers (λ(abs) = 374-407 nm, λ(PL) = 509-628 nm). Furthermore, the absorption and the emission intensities were enhanced via the light-harvesting effect by the conjugation with fluorene. Finally, we also demonstrated the dynamic reversible alterations of the optical properties of the polymer thin films by exposing to acidic or basic vapors.


Self-Reconstructed Metal-Organic Framework Heterojunction for Switchable Oxygen Evolution Reaction.
Designing metal-organic framework (MOF)-based catalysts with superior oxygen evolution reaction (OER) activity and robust durability simultaneously is highly required yet very challenging due to the limited intrinsic activity and their elusive evolution under harsh OER conditions. Herein, a steady self-reconstructed MOF heterojunction is constructed via redox electrochemistry and topology-guided strategy. Thanks to the inhibiting effect from hydrogen bonds of Ni-BDC-1 (BDC=1,4-benzenedicarboxylic acid), the obatained MOF heterojunction shows greatly improved OER activity with low overpotential of 225 mV at 10 mA cm-2 , relative to the totally reconstructed Ni-BDC-3 (332 mV). Density function theory calculations reveal that the formed built-in electric field in the MOF heterojunction remarkably optimizes the ad/desorption free energy of active Ni sites. Moreover, such MOF heterojunction shows superior durability attributed to the shielding effect of the surface-evolved NiOOH coating.


Frontal lobe meningioma presenting with schizophrenia-like symptoms: an organic cause of psychotic disorder.
A 51-year-old woman had been diagnosed and treated for schizophrenia for 10 years. Two weeks prior to admission, she developed headache and diplopia. Then, she was found unconscious and was sent to the hospital. A tumour in the left frontal lobe of the brain, causing brain herniation, was diagnosed and surgical excision of tumour was performed immediately. The psychotic symptoms of the patient were completely resolved after surgery. The histological diagnosis was meningioma. This case demonstrates an uncommon presentation of meningioma, the most common primary brain tumour. Patients presenting with psychotic symptoms may be misdiagnosed with schizophrenia, when a tumour is present, allowing the tumour to grow and causing associated complications. Early diagnosis and treatment could prevent mortality and morbidity. The treating physician should be aware of organic possibilities and carefully search for atypical presentations of psychiatric disorders in their patients.


Optimizing the performance of a reactor by reducing the retention time and addition of glycerin for anaerobically digesting manure.
Anaerobic digestion of manure is a widely accepted technology for energy production. However, only a minimal portion of the manure production in the EU is anaerobically digested and occurs predominantly in codigestion plants. There is substantial potential for biogas plants that primarily operate on manure (>90%); however, the methane yields of manure are less compared to coproducts, which is one of the reasons for manure-based biogas plants often being economically non-viable. Therefore, it is essential to begin increasing the efficiency of these biogas plants. This study investigated the effect of decreasing retention time and introducing a moderate amount of glycerin on the biogas production as methods to improve efficiency. An experiment has been conducted with two different manure types in four biogas reactors. The results of the study demonstrated that, first, it was possible to decrease the retention time to 10-15 days; however, the effect on biogas production varied per manure type. Secondly, the biogas production almost triples at a retention time of 15.6 days with an addition of 4% glycerin. The relative production-enhancing effect of glycerin did not vary significantly with both manure types. However, the absolute production-enhancing effect of glycerin differed per manure type since the biogas production per gram VS differed per manure type. Thirdly, the positive effect of the glycerin input declines with shorter retention times. Therefore, the effect of glycerin addition depends on the manure type and retention time.


Structural neuroimaging research methods in geriatric depression.
Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, there is evidence that abnormalities in specific brain structures and their interconnections confer vulnerability to the development of late-life depression. Structural magnetic resonance imaging methods can be used to identify and quantify brain abnormalities predisposing to geriatric depression and in prediction of treatment response. This article reviews several techniques, including morphometric approaches, study of white matter hyperintensities, diffusion tensor imaging, magnetization transfer imaging, t2 relaxography, and spectroscopy, that have been used to examine these brain abnormalities with a focus on the type of information obtained by each method as well as each method's limitations. The authors argue that the available methods provide complementary information and that, when combined judiciously, can increase the knowledge gained from neuroimaging findings and conceptually advance the field of geriatric depression.


Sequential PTA of abdominal aorta. Haemodynamic evaluation and IV-DSA follow-up.
A case of sequential dilatation of a subtotal stenosis of the abdominal aorta in a young subject is reported. Initial and long-term success of the procedure is recorded using haemodynamic evaluation and intravenous digital subtraction angiography (IV-DSA) follow-up on an outpatient basis. In addition, the significance of biplane aortography with IV-DSA is illustrated.


Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockade.
Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Arterial lactate and cardiac output increased to 15.3 +/- 4.2 mM and 20.8 +/- 1.5 L min(-1) respectively (mean +/- SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 +/- 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 +/- 6 vs. 69 +/- 8 beats min(-1)) and at exercise exhaustion, cardiac output (16.6 +/- 3.6 L min(-1)) and arterial lactate (9.4 +/- 3.7 mM) were attenuated with a reduction in exercise capacity from 239 +/- 42 to 209 +/- 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 +/- 10 mmHg; P < 0.05). Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.