Positive Youth Development, Life Satisfaction and Problem Behaviour Among Chinese Adolescents in Hong Kong: A Replication.
The purpose of this replication study was to examine the relationships among life satisfaction, positive youth development and problem behaviour. The respondents were 7,151 Chinese Secondary 2 (Grade 8) students (3,707 boys and 3,014 girls) recruited from 44 schools in Hong Kong. Validated assessment tools measuring positive youth development, life satisfaction and problem behaviour were used. As predicted, positive youth development was positively correlated with life satisfaction, and positive youth development and life satisfaction were negatively correlated with adolescent problem behaviour. Based on a series of structural equation models, the present findings replicated the previous findings that adolescents with a higher level of positive youth development were more satisfied with life and had lesser problem behaviour, with higher level of life satisfaction and lower level of problem behaviour mutually influencing each other. These replicated findings provide a further advance in the literature on positive youth development, particularly in the Chinese context. Implications for future research and intervention were discussed.


Anterior pituitary, thyroid, parathyroid and adrenal responses to subtotal thyroidectomy in patients with Graves' disease.
Changes in the serum levels of anterior pituitary, thyroid, parathyroid, and adrenal hormones following subtotal thyroidectomy in 31 patients with Graves' disease were investigated. In 14 patients, rapid ACTH tests were performed on the preoperative and the first, third, and seventh post-operative days. Remarkable differences were not seen with regard to the changes in anterior pituitary hormones or cortisol, compared to those seen during general surgery. As to the thyroid hormones, the serum level of triiodothyronine (T3) decreased markedly after surgery and fell to half that of the preoperative value on the first postoperative day. Thereafter, a low value of T3 was maintained during the early postoperative period. Unlike T3, the serum level of thyroxine (T4) decreased gradually until the 7th post-operative day. The levels of both epinephrine and norepinephrine increased transiently during surgery, but the serum level of norepinephrine increased again on the third postoperative day. In the postoperative period, almost half the number of patients showed an inadequate cortisol response to rapid ACTH tests. It is suggested that the unique responses, such as the rise in serum norepinephrine or an inadequate response of cortisol to ACTH, or hypocalcemia, after subtotal thyroidectomy in patients with Graves' disease is largely due to the rapid decrease of T3 in the hypothyroid state, as was noted during the postoperative period.


An improved radionuclide method for the diagnosis of gastroesophageal reflux and aspiration in children (milk scan).
A radionuclide study using technetium-99m-labelled milk feeding is described for the detection of gastroesophageal reflux and aspiration in children. A comparison of findings in 39 patients referred for both radiographic and radionuclide studies showed that barium studies were positive in 25.6% and radionuclide studies in 59% of cases, reflecting the sensitivity of the radionuclide technique. This technique is also physiological and allows prolonged patient monitoring. It is simple to perform and should prove useful in the evaluation of patients suspected of having gastroesophageal reflux and aspiration.


Diminished teratogenicity of retinoid X receptor-selective synthetic retinoids.
One feature that contraindicates the wide therapeutic use of retinoids is their teratogenicity. Synthetic retinoids are distinguishable from each other on the basis of their partial or exclusive preference in binding and activation of all-trans retinoic acid receptors (RARs) or retinoid X receptors (RXRs). Using mouse embryo limb bud cells in micromass cultures as a bioassay, we examined the inhibitory activities of a number of standard and novel retinoids on chondrogenic cell differentiation. Transient cotransfection of HeLa cells was used to measure the ability of each retinoid to induce transcription of a reporter gene by activating RAR alpha, RAR beta, RAR gamma, or RXR alpha chimeric constructs. All retinoids in this study that activated RARs to any degree in the cotransfection assay also inhibited chondrogenesis in vitro, whereas retinoids that were either specific for RXR or inactive in the cotransfection assay did not. The activity of RAR-selective agonists and the inactivity of RXR-specific agonists in the cotransfection assay correlated well with the relative teratogenicity of six of the representative retinoids studied when orally administered at day 11 to pregnant ICR mice.


Preparation and evaluation of a new combined conjugated vaccine against Klebsiella pneumonia and Pseudomonas aeruginosa.
Lower respiratory tract infections (LRTIs) have been identified by the World Health Organization as the most deadly infectious diseases and a pervasive public health problem, causing increased hospital admissions, mortality and antibiotic use. This study aims to determine the most common and resistant bacteria that cause LRTIs and prepare an appropriate vaccine to reduce and prevent potential future infections. Our survey was conducted by collecting respiratory exudate specimens. The most predominant and resistant types were Klebsiella pneumonia and Pseudomonas aeruginosa. The lipopolysaccharides (LPS) were extracted using a modified hot phenol method to prepare the vaccine. The LPS were then activated and conjugated. The immunogenicity of the prepared singles and combined vaccines was determined through an in vivo assay using BALB/c mice. The prepared vaccine provided high protection against the lethal dose of both bacteria in mice. The combined vaccine shows a significant value in achieving high immunization. These findings demonstrate the potential of the bacterial LPS molecules to be used as effective vaccines. Developing an effective single and combined vaccine against P. aeruginosa and K. pneumonia can protect and reduce LRTI incidence.


Surgical Casualty Care in Contested Distributed Maritime Operations: Lessons Learned From the Falklands War.
The Falklands Campaign was fought a significant distance from the home base of the British Fleet. The planning and delivery of medical care during this campaign can provide significant lessons for strategic medical planning in other far spread geographic locations, including the Indo-Pacific region. Consideration of doctrine, including Role 1-4 facilities and the golden hour, may need to be reconsidered in light of changing scenarios. New concepts such as the "90-in-90" and "3-in-3" are also discussed as a framework for future planning in the U.S. Indo-Pacific Command area of responsibility.


Using enzyme cascades in biocatalysis: Highlight on transaminases and carboxylic acid reductases.
Biocatalysis, the use of enzymes in chemical transformations, is an important green chemistry tool. Cascade reactions combine different enzyme activities in a sequential set of reactions. Cascades can occur within a living (usually bacterial) cell; in vitro in 'one pot' systems where the desired enzymes are mixed together to carry out the multi-enzyme reaction; or using microfluidic systems. Microfluidics offers particular advantages when the product of the reaction inhibits the enzyme(s). In vitro systems allow variation of different enzyme concentrations to optimise the metabolic 'flux', and the addition of enzyme cofactors as required. Cascades including cofactor recycling systems and modelling approaches are being developed to optimise cascades for wider industrial scale use. Two industrially important enzymes, transaminases and carboxylic acid reductases are used as examples regarding their applications in cascade reactions with other enzyme classes to obtain important synthons of pharmaceutical interest.


Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis.
To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA). This was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used. We included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%-41%; I 2 87.94%; p < 0.001): focal cSS prevalence was 14% (95% CI 12%-16%; I 2 6.75%; p = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%-26%; I 2 90.39%; p < 0.001). During a mean follow-up of 3.1 years (range 1-4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%-9.8% per year; I 2 83%; p < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%-6.1%; I 2 70%; p = 0.018) for patients without cSS, 11.1% (95% CI 7%-15.2%; I 2 56.8%; p = 0.074) for cSS presence, 9.1% (95% CI 5.5%-12.8%; I 2 0%; p = 0.994) for focal cSS, and 12.5% (95% CI 5.3%-19.7%; I 2 73.2%; p = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19-3.85; p < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31-2.41; p = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91-6.30; p < 0.0001). In patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning. This study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.


Release of histamine by neuropeptides from the perfused rat hindquarter.
The release of histamine and serotonin by neuropeptides and capsaicin was measured in the isolated perfused rat hindquarter preparation. Substance P and two antagonistic peptides, [D-Pro2, D-Phe7, D-Trp9]-SP and [D-Pro2, D-Trp7,9)]-SP, release histamine, the SP(4-11) and SP(6-11) analogues did not. VIP and somatostatin released histamine and also serotonin. No amines were released by bombesin. Thus, all amine releasing peptides possessed at least two basic charges. However, the histamine releasing activity of the neuropeptides tested did not correlate with their reported ability to cause vasodilation and plasma extravasation. The SP(4-11) and SP(6-11) analogues which did not release histamine caused plasma extravasation. It is concluded that SP causes plasma extravasation by a direct action on blood vessels. Capsaicin released only serotonin but no histamine either in untreated rats and such desensitized with capsaicin as neonates. In rats desensitized with capsaicin 4 days prior to the experiment the substance P induced histamine release was as high as in untreated controls; it was, however, absent in rats desensitized with capsaicin as neonates. It is assumed that the sensitivity of mast cells to substance P is lost after degeneration of substance P containing primary sensory fibers.


Inflammatory bowel disease and completed suicide in Danish adults.
The risk of suicide is increased among people with inflammatory bowel disease (IBD); however, most of the evidence regarding this association comes from studies of all-cause mortality, with small numbers of people who have committed suicide, or from clinical case reports. The current study examined the association between the two forms of IBD: Crohn's disease (CD) and ulcerative colitis (UC), and completed suicide in a population-based sample. Data for this nested case-control study were obtained from the Danish national healthcare and social registries. We included 27,053 cases who completed suicide between January 1, 1981, and December 31, 2006. Controls were selected from the general population and matched to cases on gender, date of birth, and calendar time (n = 551,060). There was an increased rate of suicide among participants with both CD (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1, 2.3) and UC (OR = 1.9, 95% CI: 1.4, 2.4), when adjusting for the matched factors and identified confounders. The current study suggests that physicians treating IBD patients should be vigilant about expressions of suicidal ideation or signs and symptoms of self-harm.


Immunolocalisation of two tropinone reductases in potato (Solanum tuberosum L.) root, stolon, and tuber sprouts.
Tropinone reductases (TRs) are essential enzymes in the tropane alkaloid biosynthesis, providing either tropine for hyoscyamine and scopolamine formation or providing pseudotropine for calystegines. Two cDNAs coding for TRs were isolated from potato (Solanum tuberosum L.) tuber sprouts and expressed in E. coli. One reductase formed pseudotropine, the other formed tropine and showed kinetic properties typical for tropine-forming tropinone reductases (TRI) involved in hyoscyamine formation. Hyoscyamine and tropine are not found in S. tuberosum plants. Potatoes contain calystegines as the only products of the tropane alkaloid pathway. Polyclonal antibodies raised against both enzymes were purified to exclude cross reactions and were used for Western-blot analysis and immunolocalisation. The TRI (EC 188.8.131.52) was detected in protein extracts of tuber tissues, but mostly in levels too low to be localised in individual cells. The function of this enzyme in potato that does not form hyoscyamine is not clear. The pseudotropine-forming tropinone reductase (EC 188.8.131.52) was detected in potato roots, stolons, and tuber sprouts. Cortex cells of root and stolon contained the protein; additional strong immuno-labelling was located in phloem parenchyma. In tuber spouts, however, the protein was detected in companion cells.


Identification of early senescence-associated genes in rice flag leaves.
Leaf senescence is one of the key stages of plant leaf development. It is a highly complex but ordered process involving expression of large scale senescence associated genes, and its molecular mechanisms still remain unclear. By using suppression subtractive hybridization, 815 ESTs that are up-regulated at the onset of rice flag leaf senescence have been isolated. A total of 533 unigenes have been confirmed by macroarray detection and sequencing. 183 of these unigenes have GO annotations, involved in macromolecule metabolism, protein biosynthesis regulation, energy metabolism, gene expression regulations, detoxification, pathogenicity and stress, cytoskeleton organization and flower development. Another 121 unigenes co-localized with previously reported known stay-green QTLS. RT-PCR analysis on the other novel genes indicated that they can be up-regulated in natural early senescence and induced by hormone. Our results indicate that senescence is closely related to various metabolic pathways, thus providing new insight into the onset of leaf senescence mechanism.


Prediction of prognosis in the UM-X7.1 hamster model of congestive heart failure using the Tei index.
Cardiac function is difficult to evaluate in small animal models of heart disease. The Doppler Tei index is a simple and non-invasive measure that can express global cardiac function even in small animal models of congestive heart failure. However, its ability to predict prognosis has not been evaluated. We tested the hypothesis that cardiac functional indices, such as the Tei index, can predict the prognosis of hamsters with cardiac dysfunction. The Tei index, defined as the sum of the isovolume contraction and relaxation time divided by ejection time, and the percent fractional shortening of the left ventricle was measured in 48 anesthetized male hamsters (19.7+/-0.4 weeks old) with cardiac dysfunction (UM-X7.1), using Doppler and 2-dimensional echocardiography. The hamsters were separated into 2 groups based on the median Tei index (0.50) and % fractional shortening (FS) (21%). Kaplan-Meier analysis determined the survival rates of the groups. Both the Tei index and %FS enabled significant distinction of better and poorer survival (p < 0.01), and the survival curves were less overlapped when the animals were separated according to the Tei index. The Tei index can predict prognosis in a small animal model of heart failure.


Degradation of the antifouling compound Irgarol 1051 by manganese peroxidase from the white rot fungus Phanerochaete chrysosporium.
Irgarol 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine), a derivative of s-triazine herbicide, is an antifouling compound used as an alternative to organotins. The compound is highly persistent and is known to be biodegraded only by the white rot fungus, Phanerochaete chrysosporium. We used partially purified manganese peroxidase (MnP) prepared from P. chrysosporium to evaluate its capacity to degrade Irgarol 1051. MnP degraded Irgarol 1051 to two major products, one identified as M1 (identical to GS26575, 2-methylthio-4-tert-butylamino-6-amino-s-triazine) and the other not identified but with same mass spectrum as M1 and a different ultraviolet spectrum. This report clearly demonstrates that this ligninolytic enzyme is involved in the degradation of Irgarol 1051.


Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour.
Prior splenectomy increased the resistance of BALB/c mice to a syngeneic methylcholanthrene-induced ascitic tumour inoculated i.p. The survival rate of splenectomized mice was 81-6% while those of normal and sham-operated controls were 11-5% and 20% respectively. The effect of splenectomy, however, was seen only within the dose range of 10(3) to 10(4) tumour cells. This effect of splenectomy was abolished by the transfer to mice of serum from tumour-bearing mice, and of spleen cells from normal donors, immediately after the inoculation of tumour cells. Cell-free ascitis fluid did not abolish the effect of splenectomy. The findings suggest that there is a subpopulation of spleen cells which produces a tumour growth enhancing factor which is found in the serum of tumour-bearing mice.


Mechanism and prediction of HCC development in HBV infection.
Chronic hepatitis B virus (HBV) infection remains one of the leading causes of hepatocellular carcinoma (HCC) globally. Over the past few decades, the risk factors of HCC in patients with chronic hepatitis B have been well characterized, and can be divided into host and viral factors. A few groups have also derived and validated HCC prediction scores based on these risk factors. In general, the scores have high negative predictive value in identifying a low risk group who may not need HCC surveillance in the next 3-5 years. The scores have been tested originally in Asian patients, and results on their performance in the Caucasian population are conflicting. Furthermore, new research has identified genetic factors and new virological markers (e.g. hepatitis B surface antigen and core-related antigen levels) for HCC, but they are yet to be applied in routine clinical practice.


[Peritoneal drainage without antibiotics (author's transl)].
The mortality of generalized peritonitis in serious. The drainage of the peritoneal cavity for diffuse peritonitis is essential but difficult, and it should be combined with peritoneal lavage. The drainage system must be properly adapted to the intraperitoneal liquid circulation. The local use of antibiotics is not indicated. Systemic administration is obvious, because in about 80% of cases, it is an anaerobic infection with Bacteroides fragilis, a dreadfully tough organism, which impairs the function of organs such as lung, heart, kidney, brain, and liver.


GPR120 is not required for ω-3 PUFAs-induced cell growth inhibition and apoptosis in breast cancer cells.
Intake of ω-3 PUFAs reduces the frequency of breast cancer, and GPR120 receptor transduces ω-3 PUFAs signaling to increase insulin sensitivity in mice, but whether GPR120 mediates ω-3 PUFAs signaling to inhibit breast carcinogenesis is currently unknown. In the present study, we found that GPR120 is highly expressed in human breast cancerous tissues but not adjacent normal tissue. Knockdown of GPR120 by siRNA in breast cancer cells significantly reduced cell growth, and dramatically increased ω-3 FFA-induced cell growth inhibition and apoptosis. Thus, these observations indicated that GPR120 promotes breast cancer cell growth, whereas ω-3 PUFA-induce breast cancer cell apoptosis independently of GPR120.


Tobramycin-neomycin cross-sensitivity.
Fifty normal control volunteers were patch tested to 20% neomycin as well as tobramycin 1%, 10%, 20% and 30% in white petrolatum. Tobramycin is a new aminoglycoside antibiotic for prescription ophthalmologic use in the United States. There were no reactions on any of the control volunteers. Twenty known and proven neomycin-allergic patients were then tested to tobramycin 10% and 20% in white petrolatum, as well as to neomycin 20% aqueous and 20% in white petrolatum. All 20 reacted with a 2+ or greater response to the neomycin patch tests. Twelve out of the 20 or 60% of the neomycin-allergic patients reacted to the 10% tobramycin in white petrolatum. Thirteen out of 20 or 65% reacted to 20% tobramycin in white petrolatum. From these data, tobramycin (ophthalmic) should not be used to treat known neomycin-allergic patients without first patch testing the patient with 20% tobramycin in white petrolatum. It appears probable that 65% of neomycin-allergic patients would react with a dermatitic response to such therapy.


Policy recommendations for carrier testing and predictive testing in childhood: a distinction that makes a real difference.
The genetic testing of children raises many ethical concerns. This paper examines how five position statements from Canada, UK and USA, which present guidelines for good practice in this area produce different recommendations for carrier testing and predictive testing. We find that the genetic information generated through carrier testing is routinely presented as less serious than that generated from predictive testing. Additionally, the reproductive implications of predictive testing are also routinely erased. Consequently, the papers argue strongly against predictive testing but advise caution against carrier testing in somewhat weaker terms. We argue that these differences rest on assumptions about the status of reproduction in people's lives and on an ethical stance that foregrounds the self over others. We propose that questioning the crude and sharp distinction between carrier and predictive testing in principle may enable practitioners and parents/families to make more nuanced decisions in practice.


Homeless children: their evaluation and treatment.
The number of homeless families in the United States is growing at an alarming rate. More families are becoming homeless primarily because of financial and housing problems, such as loss of job and income, loss of welfare benefits, being victims of robbery, and eviction. Many of the homeless families have complex psychosocial and medical problems. Their children have a higher prevalence than the general population of all categories of illness, including acute illnesses such as colds, fevers, and diarrhea; chronic health problems such as epilepsy and asthma; developmental delay; and behavior and mental health problems. Clinical evaluation of the homeless family and child is presented, incorporating their special needs and considerations.


Bilateral vasculopexy of anomalous vertebral arteries causing cervicomedullary compression: case report and technical note.
The authors report an extremely rare cause of cervicomedullary cord compression by anomalous ectatic vertebral arteries. A 50-year-old male patient presented with a 9 month history of progressive quadriparesis. Investigations revealed that the vertebral arteries on both sides had a mirror-like course and caused a deep indentation into the high cervical cord. Bilateral vasculopexy was done using Teflon slings. The treatment resulted in rapid recovery from symptoms. Anomalous course of the vertebral artery can result in symptoms of high cervical cord compression. Vasculopexy can result in lasting cure from symptoms.


Work-related values and satisfactions. A cross-occupational analysis of professionals vs. non-professionals in hospital dietetic services.
Job satisfaction and work values of hospital dietitians were studied and compared with those of non-professional hospital foodservice personnel. The instrument was distributed to dietitians in nine Midwestern states. Dietitians had higher job satisfaction than foodservice employees on four components: The work itself, supervision, earnings, and compatibility with co-workers. Satisfaction increased with years in the profession, with directors of dietetics being more satisfied than staff dietitians. On the work value measures, dietitians scored higher on drive, ambition, and self-concept, whereas non-professional employees tended to attribute success to luck and "knowing the right people."


Self-reported disability due to headache: a comparison of clinic patients and controls.
To compare the self-reported disability of headache sufferers who seek medical assistance with those who do not seek such help and determine possible relationships between perceived disability and psychological factors. Subjects were 51 headache patients and 53 persons without medical assistance for their headache within the past 2 years. All subjects completed a structured interview that gathered headache data, a headache disability scale, and the Minnesota Multiphasic Personality Inventory-Revised (MMPI-2). A 2 x 2 ANCOVA design was employed. Subject group (patient vs control) was the first factor and headache type (migraine vs mixed) was the second. Covariates were headache intensity and five subscales of the MMPI-2. Dependent variables were the seven subscales of the headache disability scale. Stepwise discriminant analysis was conducted to determine which factors best classified subjects as patients or controls. University Medical Center headache clinic. Clinic patients reported significantly greater disability on their occupation than controls--a difference emerging after controlling for level of headache pain and personality variables. Patients differed from controls, although not significantly, in the rank order of life activities most affected by headache. Discriminant analysis revealed that self-reported disability for occupation and the Hysteria scale from the MMPI-2 best differentiated the groups.


1-(4-Fluoro-phen-yl)-2-(1H-imidazol-1-yl)ethanol.
In the title compound, C(11)H(11)FN(2)O, the dihedral angle between the mean planes of the two rings is 1.30 (4)°. In the crystal, O-H⋯N hydrogen bonds link the mol-ecules into chains along the b axis.


[Safety assessment in radomized controlled clinical trials].
To introduce some methods of safety assessment in randomized controlled clinical trials. Recent advances and current parctice in normalized safety assessment were reviewed and relevant data analyzed. RESTULTS: The statistical issues including analysis and presentation of adverse events data and laboratory data were involved and summed up. With the progressive development of randomized controlled clinical trials in China, the methods introduced in this paper are sure to prove of consultative value for the safety assessment.


Complications associated with PlasmaBlade TnA during tonsillectomy and adenoidectomy from 2010 to 2020: A MAUDE study.
The pulsed-electron avalanche knife (PEAK) PlasmaBlade TnA (Medtronic, n.d.) is a relatively new electrosurgical technology that is used widely in head and neck surgery (Medtronic Manuals, n.d.). This study aims to summarize device malfunctions, patient complications, and subsequent interventions related to PEAK PlasmaBlade TnA during tonsillectomy and adenoidectomy. The US Food and Drug Administration's Manufacture and User Facility Device Experience database was queried for reports of PlasmaBlade TnA adverse events from June 6, 2009, to August 30, 2020. Data were extracted from reports pertaining to tonsillectomy with or without adenoidectomy. 128 reports were identified, from which 163 adverse events were extracted. Of these, 23 (14.6%) were related to patients, and 140 (85.4%) were related to device malfunction. The most frequently reported patient-related adverse event was a burn injury (17 [73.9%]). The most common device malfunctions were dislodgment of device component (39 [27.9%]), followed by tip ignition (32 [22.9%]), damaged tip or wire during operation (28 [20%]), and melted device (24 [17.1%]). PEAK PlasmaBlade TnA have demonstrated utility in tonsillectomy with or without adenoidectomy but are associated with adverse events. Interventions aimed at improving both physician and patient education may help reduce adverse events attributed to improper use. Further study is needed to clarify optimal approaches to education.


Mutations of key substrate binding residues of leishmanial peptidase T alter its functional and structural dynamics.
M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of oligopeptides during the terminal stages of protein degradation pathway to maintain turnover. Therefore, specific inhibition of PepT bores well for the development of novel next-generation antileishmanials. This work describes the metal dependence, substrate preferences and inhibition of PepT, and demonstrates in detail the role of its two conserved substrate binding residues. PepT was purified and characterized using a scheme of peptide substrates and peptidomimetic inhibitors. Residues T364 and N378 were mutated and characterized with an array of biochemical, biophysical and structural biology methods. PepT sequence carries conserved motifs typical of M20 peptidases and our work on its biochemistry shows that this cytosolic enzyme carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently, while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364 and N378) to alanine affects structure, reduces substrate binding and alters the amidolytic activity of this dimeric enzyme. PepT preferentially hydrolyzes oligopeptides carrying alanine at P1 position and is potently inhibited by peptidomimetics. Reduced substrate binding after mutations was a key factor involved in amidolytic digressions. This study provides insights for further exploration of the druggability of PepT and highlights prospective applications of this enzyme along with its mutazyme T364A/N378A.


Dispersal syndromes of Vachellia caven: Dismantling introduction hypotheses and the role of man as a conceptual support for an archaeophyte in South America.
Vachellia caven has a disjunct distribution at the southern cone of South America, occupying two major ranges: west of Andes (Central Chile) and east of them (mainly the South American Gran Chaco). For decades, the species has been subject to various ecological and natural history studies across its distribution, but questions concerning its origin in the western range remain unresolved. Thus far, it is unclear whether Vachellia caven was always a natural component of the Chilean forests, and "how" and "when" the species arrived in the country. In this study, we revised the dispersal syndromes of the species and contrast the two main hypotheses of dispersion to the west of Andes that have been proposed in the 90's, namely animal versus human-mediated dispersal. For this, we reviewed all scientific literature on the species and explored the available information on morphology, genetics, fossil records and distribution patterns of closely related species. Here we illustrate how the collected evidence provides support for the human-mediated dispersal hypothesis, by including a conceptual synthesis that summarizes the outcomes of different dispersal scenarios. Lastly, and regarding the positive ecological effects this species has in the introduced area, we suggest reconsidering the (underappreciated) historical impacts of archaeophytes and rethinking the role that indigenous human tribes may have had in the dispersion of different plants in South America.


Thymus-independent induction and antigen-dependent recovery of idiotype-specific suppression.
BALB/c nude (nu/nu) mice and euthymic (nu/+) littermates were treated as neonates with anti-T15 antibody and challenged at various ages with either a thymus-independent, PC-Brucella abortus (PC-BA), or thymus-dependent, PC-keyhole limpet hemocyanin (PC-KLH), form of phosphorylcholine (PC). Nu/nu mice challenged with PC-KLH received KLH-primed splenic T cells prior to immunization. Neither neonatally anti-idiotype-treated nu/+ nor nu/nu mice responded with the production of T15-positive anti-PC antibodies after challenge with either form of PC antigen. It is concluded that neither induction nor maintenance of a state of T15-specific suppression requires thymus-matured T cells. Recovery of anti-PC responsiveness in suppressed nu/+ or nu/nu mice was similar and was found to be related to the form of antigen used to elicit the response. Immunization with PC-KLH revealed a long-lasting unresponsiveness (up to 16 weeks). In contrast, immunization with PC-BA elicited a full anti-PC response as early as at 6.5 weeks of age.


An apoptosis inhibitor suppresses microglial and astrocytic activation after cardiac ischemia/reperfusion injury.
Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that the apoptosis inhibitor, Z-VAD, attenuates microglial and astrocytic hyperactivation and brain inflammation in rats with cardiac I/R injury. Rats were subjected to either sham or cardiac I/R operation (30 min-ischemia followed by 120-min reperfusion), rats in the cardiac I/R group were given either normal saline solution or Z-VAD at 3.3 mg/kg via intravenous injection 15 min prior to cardiac ischemia. Left ventricular ejection fraction (% LVEF) was determined during the cardiac I/R protocol. The brain tissues were removed and used to determine brain apoptosis, brain inflammation, microglial and astrocyte morphology. Cardiac dysfunction was observed in rats with cardiac I/R injury as indicated by decreased %LVEF. In the brain, we found brain apoptosis, brain inflammation, microglia hyperactivation, and reactive astrogliosis occurred following cardiac I/R injury. Pretreatment with Z-VAD effectively increased %LVEF, reduced brain apoptosis, attenuated brain inflammation by decreasing IL-1β mRNA levels, suppressed microglial and astrocytic hyperactivation and proliferation after cardiac I/R injury. Z-VAD exerts neuroprotective effects against cardiac I/R injury not only targeting apoptosis but also microglial and astrocyte activation.


Preparation of poly(trimethyl-2-methacroyloxyethylammonium chloride-co-ethylene glycol dimethacrylate) monolith and its application in solid phase microextraction of brominated flame retardants.
A capillary poly(trimethyl-2-methacroyloxyethylammonium chloride-co-ethylene glycol dimethacrylate) monolith was in situ synthesized by thermally initiated free radical co-polymerization using trimethyl-2-methacroyloxyethylammonium chloride (MATE) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. N,N-dimethylformamide and polyethylene glycol 6000 were used as solvent and porogen, respectively. The morphology and porous structure of the resulting monoliths were assessed by scanning electron microscope. In order to prepare practically useful poly(MATE-co-EGDMA) monoliths with low flow resistance and good mechanical strength, some parameters such as PEG-6000 to DMF ratio, total monomer to porogen ratio, and crosslinker to monomer ratio were optimized systematically. Moreover, the extraction mechanism was evaluated using two series of compounds, alkylbenzenes and weak acids, as model compounds on poly(MATE-co-EGDMA) monoliths as liquid chromatographic stationary phase. Finally, the monoliths were applied as the solid phase microextraction medium, and a simple off-line method for simultaneous determination of three brominated flame retardants, 2,4,6-tribromophenol (TBP), tetrabromobisphenol A (TBBPA) and 4,4'-dibrominated diphenyl ether (DBDPE), in environmental waters was developed by coupling the polymer monolith microextraction to HPLC with UV detection. The regression equations for these three brominated flame retardants showed good linearity from their limit of quantification to 5000ng/mL. The limits of detection were 0.20, 0.15 and 0.10ng/mL for TBP, TBBPA and DBDPE, respectively. The recovery of the proposed method was 78.7-106.1% with intra-day relative standard deviation of 1.3-4.4%.


Development of a Novel Anti-Mouse CCR2 Monoclonal Antibody (C2Mab-6) by N-Terminal Peptide Immunization.
The CC chemokine receptor type-2 (CCR2) belongs to the G-protein-coupled receptor superfamily, expressed on the cell surface of immune cells and tumors. CCR2 binds to the CC motif chemokine 2/monocyte chemoattractant protein-1, a CC chemokine, which is produced by various cells, including immune-related cells and tumors. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CCR2 has been desired for treatment and diagnosis. This study established a novel, specific, and sensitive anti-mouse CCR2 (mCCR2) mAb; C2Mab-6 (rat IgG1, kappa), using the mCCR2 synthetic peptide immunization method. C2Mab-6 reacted with mCCR2-overexpressed Chinese hamster ovary-K1 cells and L1210 (murine leukemia) cells, which express endogenous mCCR2 in flow cytometry. Furthermore, C2Mab-6 showed a high binding affinity for both cells. Hence, C2Mab-6 can be a useful tool for analyzing mCCR2-related biological responses, using flow cytometry.


Factors influencing quantified surface EMGs.
Isometric flexions of the elbow are studied in man. For the three joint angles studied, the torque, the surface EMG of the biceps brachii muscle, and the quantified EMG are recorded. The EMGs are picked up by means of bipolar electrodes located in such a way as to vary the interelectrode orientation, the interelectrode distance and the position on the muscle. Longitudinal placements collect stronger signals that transverse ones. Under certain conditions, the magnitude of the quantified EMG depends on the distance between the electrodes, and on their location on the muscle. The results are discussed in terms of conduction volume and detection volume.


Reliability of echocardiography in the detection of metastatic malignant pericardial masses.
Pericardial metastasis is a rare localization of a malignant neoplasm. We report a 28-year-old man with metastatic spread of an epithelial thymoma into the pericardium. This in turn compressed the heart with induction of exertional dyspnea, hepatomegaly, chest pain and increased jugular venous pressure. All these features occurred in the absence of significant hemodynamic impairment. Echocardiography revealed an intrapericardial mass at the level of the left ventricular free wall. Surgical removal of this pericardial neoplasm produced a rapid improvement in clinical status. Ultrasonography, therefore, is a reliable noninvasive method for the diagnosis of cardiac impairment due to a pericardial metastatic mass.


Hypoxia enhances buffalo adipose-derived mesenchymal stem cells proliferation, stemness, and reprogramming into induced pluripotent stem cells.
Adipose tissue-derived mesenchymal stem cells (ASCs) from livestock are valuable resources for animal reproduction and veterinary therapeutics. Previous studies have shown that hypoxic conditions were beneficial in maintaining the physiological activities of ASCs. However, the effects of hypoxia on buffalo ASCs (bASCs) remain unclear. In this study, the effects of hypoxia on proliferation, stemness, and reprogramming into induced pluripotent stem cells (iPSCs) of bASCs were examined. The results showed that the hypoxic culture conditions (5% oxygen) enhanced the proliferation and colony formation of bASCs. The expression levels of proliferation-related genes, and secretion of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were significantly enhanced in hypoxia. Hypoxic culture conditions activated hypoxia-inducible factor-1α (HIF-1α), thereby contributing to the secretion of bFGF and VEGF, which in turn enhanced the expression of HIF-1α and promoted the proliferation of bASCs. Furthermore, in hypoxic culture conditions, bASCs exhibited the main characteristics of mesenchymal stem cells, and the expression levels of the pluripotent markers OCT4, NANOG, C-MYC, and the differentiation capacity of bASCs were significantly enhanced. Finally, bASCs were more efficiently and easily reprogrammed into iPSCs in hypoxic culture conditions and these iPSCs exhibited some characteristics of naïve pluripotent stem cells. These findings provide the theoretical guidance for elucidating the detailed mechanism of hypoxia on physiological activities of bASCs including proliferation, stemness maintenance, and reprogramming.


Organocatalytic Asymmetric Mannich Reaction of 3-Hydroxyoxindoles/3-Aminooxindoles with in Situ Generated N-Boc-Protected Aldimines for the Synthesis of Vicinal Oxindole-Diamines/Amino Alcohols.
A highly efficient asymmetric Mannich reaction of 3-monosubstituted 3-aminooxindoles/3-hydroxyoxindoles with in situ generated N-Boc-protected aldimines catalyzed by the chiral bifunctional thiourea-tertiary amine catalyst has been developed. Under mild reaction conditions, a series of structurally diverse vicinal oxindole-diamines/amino alcohols were smoothly obtained in moderate to high yields (up to 99%) with good to excellent diastereoselectivities and enantioselectivities (up to 95:5 dr and 96% ee). The synthetic application of this protocol was also demonstrated by the versatile transformation of chiral vicinal oxindole-diamine/amino alcohol into spirocyclic oxindoles.


Membrane-bound sorbitol 6-phosphatase in fat body cells controls the dynamics of sorbitol 6-phosphate, a major hemolymph sugar in the silkworm.
Sorbitol 6-phosphate (S6P) is one of two major sugars (another is trehalose) in the larval hemolymph of Bombyx mori, and its amount dramatically decreases concomitantly with the onset of prepupal period. In the last (fifth) instar larvae, the amount of S6P is approximately 30 micromol/larva at its maximum and decreases to less than 1 micromol at the wandering stage. Incubation of fat bodies of wandering larvae with S6P generates sorbitol in the medium, while S6P in the medium decreases, indicating that fat body possesses sorbitol 6-phosphatase (S6Pase) activity. S6Pase activity in the fat body remains low during the feeding period, abruptly increases at the wandering and decreases to a low level after gut purge. 20-Hydroxyecdysone (20E) increases S6Pase activity in the fat body of feeding larvae, and the activation is dose-dependent. Cell fractionation studies show that S6Pase is mainly associated with the membrane and the optimal pH for membrane-bound S6Pase is 5.5, which is different from that for soluble acid phosphatase (pH 4). Present findings indicate that the S6Pase responsible for a decrease in hemolymph S6P is membrane-bound, and its activity is controlled by a rise of hemolymph ecdysteroid titer at the onset of the wandering stage.


Adverse effects of equine rabies immune gobulin.
Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.


Protein 53, B-Cell Lymphoma-2, Cyclooxygenase-2, and CD105 Reactivity in Keratocystic Odontogenic Tumors: An Immunohistochemical Analysis.
The objective is to evaluate and compare immunohistochemically, the biological behavior of keratocystic odontogenic tumor (KCOT) with normal oral mucosa by analyzing cell proliferation, angiogenesis, and antiapoptosis using cyclooxygenase-2 (COX-2), protein 53 (p53), B-cell lymphoma-2 (Bcl-2), and CD105 (endoglin). The present study comprised 30 cases of KCOT in the study group, in which the expression of COX-2, p53, Bcl-2, and CD105 were analyzed and compared with that of control group consisting of 30 normal oral mucosae. The results were evaluated based on a number of positively stained cells; among 30 samples of KCOT, 22 samples were p53 positive, 23 samples were Bcl-2 positive, 18 samples were COX-2 positive, whereas all the above markers were negative in all the 30 samples of the normal oral mucosa and CD105 mean vascular density in KCOT 13.8 in normal oral mucosa. The present study suggests that angiogenesis, cell proliferation, and antiapoptosis may be the possible factors contributing for the unique biological behavior of KCOT.


Eating disturbances in female prisoners: the role of anger.
Women in prison have high levels of impulsive damaging behaviours, including disordered eating. In addition, they display pathological levels of the emotional precursors that have been associated with eating disorders, particularly anger. The present study examines levels of disordered eating behaviours in female prisoners, and whether those behaviours are associated with anger. The sample consisted of 91 sentenced women at a medium-sized prison in the UK. The women completed an interview-based screening tool for eating disorders, alongside a standardised measure of anger. Using the established cut-off on the measure concerned, 25% of the women were at risk for an eating disorder. This prevalence rate is exactly twice that observed in a non-eating-disordered community sample, using the same measure. Furthermore, different facets of anger were associated with different aspects of eating psychopathology. The most plausible explanation for this association appears to be that many women enter prison with high levels of anger-driven impulsivity, and that the constraints of the prison environment result in a focus on eating behaviours. Future research directions are discussed.


Plant protein kinase substrates identification using protein microarrays.
Protein kinases regulate signaling pathways by phosphorylating their targets. They play critical roles in plant signaling networks. Although many important protein kinases have been identified in plants, their substrates are largely unknown. We have developed and produced plant protein microarrays with more than 15,000 purified plant proteins. Here, we describe a detailed protocol to use these microarrays to identify plant protein kinase substrates via in vitro phosphorylation assays on these arrays.


Characterization of a novel psyllid-transmitted waikavirus in carrots.
Carrots collected from the Western Negev region in Israel during the winter of 2019 showed disease symptoms of chlorosis, leaf curling, a loss of apical dominance, and multiple lateral roots that were not associated with known pathogens of the carrot yellows disease. Symptomatic carrots were studied for a possible involvement of plant viruses in disease manifestations using high throughput sequencing analyses. The results revealed the presence of a waikavirus, sharing a ∼70% nucleotide sequence identity with Waikavirus genus members. Virions purified from waikavirus-positive carrots were visualized by transmission electron microscopy, showing icosahedral particle diameter of ∼28 nm. The genome sequence was validated by overlapping amplicons by designed 12 primer sets. A complete genome sequence was achieved by rapid amplification of cDNA ends (RACE) for sequencing the 5' end, and RT-PCR with oligo dT for sequencing the 3' end. The genome encodes a single large ORF, characteristic of waikaviruses. Aligning the waikavirus-deduced amino-acid sequence with other waikavirus species at the Pro-Pol region, a conserved sequence between the putative proteinase and the RNA-dependent RNA polymerase, showed a ∼40% identity, indicating the identification of a new waikavirus species. The amino-acid sequence of the three coat proteins and cleavage sites were experimentally determined by liquid chromatography-mass spectrometry. A phylogenetic analysis based on the Pro-Pol region revealed that the new waikavirus clusters with persimmon waikavirus and actinidia yellowing virus 1. The new waikavirus genome was localized in the phloem of waikavirus-infected carrots. The virus was transmitted to carrot and coriander plants by the psyllid Bactericera trigonica Hodkinson (Hemiptera: Triozidae).


Evaluation of mutagenic and genotoxic activities of lobeline and its modulation on genomic instability induced by ethanol.
Lobeline is a natural alkaloid derived from Lobelia inflata that has been investigated as a clinical candidate for the treatment of alcoholism. In a pre-clinical trial, lobeline decreased the preference for and consumption of ethanol, due to the modulation of the nicotinic acetylcholine receptor. However, the interaction between lobeline and ethanol is poorly known and thus there are safety concerns. The present study was conducted to evaluate the mutagenic and genotoxic effects of lobeline and assess its modulation of ethanol-induced toxicological effects. CF-1 male mice were divided into five groups. Groups received an intraperitoneal injection of saline solution, lobeline (5 or 10mg/kg), ethanol (2.5 g/kg), or lobeline plus ethanol, once a day for three consecutive days. Genotoxicity was evaluated in peripheral blood using the alkaline comet assay. The mutagenicity was evaluated using both Salmonella/microsome assay in TA1535, TA97a, TA98, TA100, and TA102 Salmonella typhimurium strains and the micronucleus test in bone marrow. Possible liver and kidney injuries were evaluated using biochemical analysis. Lobeline did not show genotoxic or mutagenic effects and did not increase the ethanol-induced genotoxic effects in blood. Lobeline also protected blood cells against oxidative damage induced by hydrogen peroxide. Biochemical parameters were not altered, indicating no liver or kidney injuries or alterations in lipid and carbohydrate metabolisms. These findings suggest that lobeline does not induce gene or chromosomal mutations, and that this lack of genetic toxicity is maintained in the presence of ethanol, providing further evidence of the safety of this drug to treat alcohol dependence.


Survey of the incidence of anaplasmosis among Nigerian Zebu trade cattle.
Sera samples from 573 Nigerian Zebu trade cattle were evaluated by the rapid card agglutination test for antibodies to Anaplasma marginale between May and July 1977. The results showed 34 per cent reactors as against 66 per cent negatives. The above results showed a significant level of exposure to the infection among the Fulani cattle managed under a husbandry system in which there is no provision for tick control. The significance of this level of exposure to Anaplasma marginale in relation to the livestock industry of the country and the need for a nation-wide anaplasmosis survey are discussed.


Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer.
Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer.


A European perspective on immunotherapy for food allergies.
Food allergies are common, and frequently, the only treatment option is strict avoidance. Unfortunately, many patients accidentally ingest allergenic foods, which can result in severe anaphylactic reactions. Several immunotherapies are being developed for food allergies; these involve oral, sublingual, epicutaneous, or subcutaneous administration of small amounts of native or modified allergens to induce immune tolerance. Oral immunotherapy seems to be the most promising approach based on results from small uncontrolled and controlled studies. However, it is a challenge to compare results among immunotherapy trials because of differences in protocols. Studies conducted thus far have tested the most prevalent food allergens: it is not clear whether their results can be extended to other allergens. Sublingual administration of immunotherapy has shown some efficacy and fewer side effects than oral administration in some trials, yet neither approach can be recommended for routine practice. Controlled studies with larger numbers of subjects are needed to determine short- and long-term efficacy and side effects. In Europe immunotherapy trials for food allergies face many ethical and regulatory issues. Guidelines from the European Medicine Agency on the clinical development of products for specific immunotherapy of allergic diseases do not adequately address immunotherapy for food allergies, especially for therapies that orally administer native food or that include pediatric patients.


Detection of human immunodeficiency virus type 1 RNA by in situ hybridization in oral mucosa epithelial cells from anti-HIV-1 positive patients.
Several in vitro studies have shown that HIV-1 can infect CD4 negative epithelial cells of different origin including normal human oral keratinocytes, but whether this infection of mucosal epithelial cells occurs in vivo is still unclear. In this report, the presence and cell types infected by HIV-1 in paraffin embedded oral mucosa biopsies from 17 anti-HIV-1 positive patients have been examined by in situ hybridization and immunohistochemistry. As controls, oral mucosa biopsies from eight patients without HIV-1 infection markers were also analyzed. The results showed that 8 out of the 17 anti-HIV-1 positive patients had HIV-1 RNA detectable in plasma. Positive hybridization signals were observed in the mucosa biopsies from 14 of the 17 anti-HIV-1 patients (82.3%). The mean percentage of cells showing HIV-1 RNA was 2.64% +/- 1.77% (range: 1% to 5.5%). No differences in the mean percentage of HIV-1 infected cells were found between patients with and without HIV-1 RNA in plasma (3.01% +/- 1.57% vs. 3.4% +/- 1.27% respectively), or between untreated patients and patients under antiretroviral therapy (2.83% +/- 1.63% vs. 3.42% +/- 1.29% respectively). Immunohistochemical detection of S-100 antigen, cytokeratin and CD4 showed that hybridization signals appeared in cytokeratin positive cells and CD4 positive cells but not in S-100 positive cells. In conclusion, this study has demonstrated that HIV-1 infects and replicates in oral mucosa epithelial cells in vivo and that these cells could represent a reservoir of the virus that may escape to the currently used antiretroviral therapy.


One size does not always fit all in value assessment.
Laying a clear path for incorporating reliable evidence on heterogeneity in value assessments could improve their applicability for healthcare decision making.


Shedding light on stem cells: Optogenetics uncover the role of ERK dynamics in pluripotency.
In this issue of Developmental Cell, Arekatla et al. use optogenetic technologies to dissect the roles of ERK and AKT dynamics in pluripotency. They show how mouse embryonic stem cells can retain memory of signaling events controlling their fate.


Acute elevation of intracranial pressure following transection of non-functional spinal cord.
A spinal cord which is neurologically nonfunctional may be functioning as a conduit for CSF between the ventricular system and the spinal subarachnoid space. Interruption of this pathway can have catastrophic consequences unless there is an adequately functioning shunt.


Rapid emergence and predominance of a broadly recognizing and fast-evolving norovirus GII.17 variant in late 2014.
Norovirus genogroup II genotype 4 (GII.4) has been the predominant cause of viral gastroenteritis since 1996. Here we show that during the winter of 2014-2015, an emergent variant of a previously rare norovirus GII.17 genotype, Kawasaki 2014, predominated in Hong Kong and outcompeted contemporary GII.4 Sydney 2012 in hospitalized cases. GII.17 cases were significantly older than GII.4 cases. Root-to-tip and Bayesian BEAST analyses estimate GII.17 viral protein 1 (VP1) evolves one order of magnitude faster than GII.4 VP1. Residue substitutions and insertion occur in four of five inferred antigenic epitopes, suggesting immune evasion. Sequential GII.4-GII.17 infections are noted, implicating a lack of cross-protection. Virus bound to saliva of secretor histo-blood groups A, B and O, indicating broad susceptibility. This fast-evolving, broadly recognizing and probably immune-escaped emergent GII.17 variant causes severe gastroenteritis and hospitalization across all age groups, including populations who were previously less vulnerable to GII.4 variants; therefore, the global spread of GII.17 Kawasaki 2014 needs to be monitored.


Relating critical and limiting fluxes to metastable and long-term stable fluxes in colloidal membrane filtration through collision-attachment theory.
In membrane technology for water/wastewater treatment, the concepts of critical flux (JC) and limiting flux (JL) suggest the existence of a threshold flux below which no fouling occurs. However, their important roles on stable flux duration have not been sufficiently understood. This work adopts a collision-attachment approach to clarify the relationship of JC, JL to metastable (i.e., short-term stable) and long-term stable fluxes based on their dependence on initial flux (J0), foulant-clean-membrane energy barrier (Ef-m), and foulant-fouled-membrane energy barrier (Ef-f). When J0 is below JL, water flux remains stable over a long time even for the case of J0 over JC, thanks to the strongly repulsive Ef-f. At J0 > JL and J0 > JC, the water flux is unstable at the beginning of filtration, and the flux ultimately decreases to JL as the long-term stable flux. Under the condition of JL < J0 ≤ JC, an initial metastable flux appears owing to the high Ef-m, with longer metastable period observed at lower J0 and for more hydrophilic/charged membrane or colloids. Nevertheless, rapid flux decline occurs subsequently due to the energy barrier shifting to weak Ef-f, and the water flux eventually degenerates to JL in long-term fouling duration. Our results provide significant guidelines for fouling control strategies with respect to membrane design, feedwater pretreatment, and operational optimization.


Lactic acidosis in childhood: Part II.
Lactic acidosis is associated with both inherited and acquired metabolic diseases. Lactic acid metabolism in the presence of altered gluconeogenesis, anaerobic glycolysis, and acid-base balance is a major factor in many disorders. Lactic acid can be formed only from pyruvic acid; therefore, disorders that increase pyruvate concentration, enhance lactic acid formation, or reduce lactic acid degradation cause lactic acidosis. Inborn metabolic errors that are accompanied by derangement of metabolic pathways of glucose, pyruvate, amino acids, and organic acids as well as toxic and systemic conditions that promote tissue hypoxia or mitochondrial injury result in lactic acidosis. In the presence of acquired disorders, treatment is directed initially toward modification or cure of the primary condition and then toward eliminating acidosis and other metabolic complications. Specific therapy is available for some inborn errors of metabolism.


Cyanamide given ICV or systemically to the rat alters subsequent alcohol drinking.
Cyanamide or disulfiram serves to suppress volitional intake of alcohol presumably because of the toxic build-up of acetaldehyde dehydrogenase (AIDH). However, the presence of acetaldehyde systemically favors the in vivo synthesis of addictive-like metabolites in the brain which in turn enhance alcohol drinking. The purpose of this investigation, therefore, was to determine whether cyanamide administered to the rat, which did not have access to alcohol during treatment, would nevertheless affect the subsequent preference for alcohol. In the first experiment, cannulae were implanted bilaterally above the cerebral ventricle of 33 adult male Sprague-Dawley rats so that an artificial CSF or a solution of cyanamide could be infused intracerebroventricularly (ICV). Following post-operative recovery, each rat was tested for its alcohol preference by offering it water and a solution of ethyl alcohol which was increased over 8 days from 3-20%. After a single test concentration of alcohol (range of 5-9%) was selected for each individual animal presented with water over a 5-day interval, cyanamide was infused in a volume of 2.5 microliters per side three times daily for 4 days in one of the following total doses: 0.03, 0.1, 0.3, 0.5 or 1.0 mg. A second five-day preference test was run, and 6 weeks following cyanamide infusions a final 3-20% alcohol preference screen was run over 8 days. The results showed that a long-term, dose-dependent increase or decrease in alcohol intake occurred in those rats reactive to the drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultrasound-assisted heterogeneous activation of persulfate by nano zero-valent iron (nZVI) for the propranolol degradation in water.
This study investigated the degradation of propranolol (PRO), a beta (β)-blockers, by nano zero-valent iron (nZVI) activated persulfate (PS) under ultrasonic irradiation. Effects of several critical factors were evaluated, inclusive of PS concentration, nZVI dosage, ultrasound power, initial pH, common anions, and chelating agent on PRO degradation kinetics. Higher PS concentration, nZVI dosage and ultrasound power as well as acidic pH favored the PRO degradation. Conversely, anions and chelating agent took on the inhibitory effect towards PRO degradation to different extents. Furthermore, the variations of morphology and surface composition of nZVI before and after the reaction were characterized by TEM, XRD and XPS. Finally, on the basis of identified degradation intermediates by LC/MS/MS analysis, this work tentatively proposed the degradation pathways. These encouraging results suggest that US/nZVI/PS process is a promising strategy for the treatment of PRO-induced water pollutant.


miR-874-3p mitigates cisplatin resistance through modulating NF-κB/inhibitor of apoptosis protein signaling pathway in epithelial ovarian cancer cells.
The resistance to cisplatin, the most common platinum chemotherapy drug, may confine the efficacy of treatment in epithelial ovarian cancer patients. Aberrant expression of inhibitor of apoptosis proteins set the stage for resistance to cisplatin in EOC; besides, chemosensitivity in EOC can be chalked up to dysregulation of specific miRNAs. Herein, we investigated whether there is a potential correlation between miR-874-3p and the X-chromosome-linked inhibitor of apoptosis, a member of the IAP protein family in cisplatin-resistant EOC cells. The lower expression of miR-874-3p was found in SKOV3-DDP cells; it was also in association with cisplatin-resistance in EOC cells. XIAP was found to contribute to developing platinum resistance and is an authentic target for miR-874-3p in SKOV3-DDP cells. Consistently, restoration of miR-874-3p expression reversed cisplatin resistance in such cells by modulating XIAP and NF-κB/Survivin signaling pathway. Besides, siRNA knock down of XIAP in SKOV3-DDP cells had an anti-migratory effect like those with miR-874 overexpression. Importantly, the enforced expression of XIAP rescued SKOV3-DDP cells from the cytotoxic effects of miR-874-3p. Finally, miR-874-3p sensitized EOC cells to cisplatin-induced apoptosis, at least in part, through targeting XIAP. The cytotoxic effects of miR-874-3p can be attributed to the targeting XIAP in cisplatin-resistant EOC cells. We believe that the combination of cisplatin with miR-874-3p may make a potential strategy to reverse cisplatin resistance.


Haematological, serological and pathological effects in chicks of one or more intravenous injections of Salmonella gallinarum endotoxin.
Abnormalities appeared a few hours after groups of 14-day-old chicks (Gallus domesticus) were injected intravenously with 15 mg/kg of endotoxin (LPS) from Salmonella gallinarum. Clinical illness without mortality was accompanied by significant (P less than 0.05) falls in body temperature, bursa weight, the main haematological parameters, serum iron (SI) and transferrin saturation (TS) and a significant increase in unsaturated iron-binding capacity. All responses, apart from bursa weight, SI values and total and differential white-cell counts, returned to normal within 24 to 48 h. LPS given daily for three consecutive days did not cause changes in the main haematological parameters during the 48 h period following the third injection. However body and bursa weight and heterophil counts were significantly depressed, whereas body temperature, SI and TS were affected biphasically, being first depressed and then raised above normal. Chicks injected with LPS daily for six consecutive days showed broadly similar responses but a persistent microcytosis was also present.


Pathogenesis and treatment of endocarditis.
The rabbit model has been invaluable for in vivo studies in the pathogenesis and treatment of bacterial endocarditis. Both of the features of the mature bacterial vegetations in this rabbit model, i.e., absence of phagocytosis and decreased metabolic activity, provide evidence to support the concept that a rapidly bactericidal antimicrobial agent provides the optimal approach to the successful treatment of endocarditis. Imipenem, a carbapenem with a very broad spectrum of in vitro activity, has been shown to be rapidly bactericidal in animals and highly effective in the treatment of experimental bacterial endocarditis. In addition, twenty-six patients with endocarditis, caused largely by Staphylococcus aureus, have been successfully treated with imipenem/cilastatin.


Gender Disparities in Epidemiology, Treatment, and Outcome for Head and Neck Cancer in Germany: A Population-Based Long-Term Analysis from 1996 to 2016 of the Thuringian Cancer Registry.
This study determined with focus on gender disparity whether incidence based on age, tumor characteristics, patterns of care, and survival have changed in a population-based sample of 8288 German patients with head neck cancer (HNC) registered between 1996 and 2016 in Thuringia, a federal state in Germany. The average incidence was 26.13 ± 2.89 for men and 6.23 ± 1.11 per 100,000 population per year for women. The incidence peak for men was reached with 60-64 years (63.61 ± 9.37). Highest incidence in females was reached at ≥85 years (13.93 ± 5.87). Multimodal concepts increased over time (RR = 1.33, CI = 1.26 to 1.40). Median follow-up time was 29.10 months. Overall survival (OS) rate at 5 years was 48.5%. The multivariable analysis showed that male gender (Hazard ratio [HR] = 1.44; CI = 1.32 to 1.58), tumor subsite (worst hypopharyngeal cancer: HR = 1.32; CI = 1.19 to 1.47), and tumor stage (stage IV: HR = 3.40; CI = 3.01 to 3.85) but not the year of diagnosis (HR = 1.00; CI = 0.99 to 1.01) were independent risk factors for worse OS. Gender has an influence on incidence per age group and tumor subsite, and on treatment decision, especially in advanced stage and elderly HNC patients.


Protection by novel vaccine candidates, Mycobacterium tuberculosis ΔmosR and ΔechA7, against challenge with a Mycobacterium tuberculosis Beijing strain.
Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), infects over two billion people, claiming around 1.5 million lives annually. The only vaccine approved for clinical use against this disease is the Bacillus Calmette-Guérin (BCG) vaccine. Unfortunately, BCG has limited efficacy against the adult, pulmonary form of tuberculosis. This vaccine was developed from M. bovis with antigen expression and host specificity that differ from M. tuberculosis. To address these problems, we have designed two novel, live attenuated vaccine (LAV) candidates on an M. tuberculosis background: ΔmosR and ΔechA7. These targeted genes are important to M. tuberculosis pathogenicity during infection. To examine the efficacy of these strains, C57BL/6 mice were vaccinated subcutaneously with either LAV, BCG, or PBS. Both LAV strains persisted up to 16 weeks in the spleens or lungs of vaccinated mice, while eliciting minimal pathology prior to challenge. Following challenge with a selected, high virulence M. tuberculosis Beijing strain, protection was notably greater for both groups of LAV vaccinated animals as compared to BCG at both 30 and 60 days post-challenge. Additionally, vaccination with either ΔmosR or ΔechA7 elicited an immune response similar to BCG. Although these strains require further development to meet safety standards, this first evidence of protection by these two new, live attenuated vaccine candidates shows promise.


Neonatal cerebral pathology diagnosed by ultrasound.
This article discusses cranial ultrasonography in various clinical settings. Since 1979, the authors have screened all preterm infants for intracranial hemorrhage, and here they present their experience with hemorrhage and its sequel, ventricular dilatation. Also discussed is the use of cranial ultrasonography in infants with seizures and encephalopathy and in infants with abnormal head growth or suspected cerebral malformations.


Does Problematic Substance Use Moderate Efficacy of Cognitive Behavioral Therapy for Adherence and Depression in HIV?
Problematic substance use may attenuate the effect of treating depression in people living with HIV (PLWH). We examined the potential moderating effect of problematic substance use on depression and adherence outcomes in PLWH (N = 143) who participated in a randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) and were randomized to either CBT-AD or enhanced treatment as usual (ETAU). Problematic substance use was operationalized as either having substance use-related diagnosis or current substance use in the past 30 days with a lifetime history of problematic use. Acute (baseline to 4-month) and follow up (4, 8, and 12-month) general linear modeling with time, condition, problematic baseline substance use, and corresponding interactions demonstrated that substance use did not significantly moderate the effects of CBT-AD on adherence or depression improvements. Therefore, CBT-AD was beneficial for PLWH with depression, regardless of problematic substance use when starting depression treatment. Based on these results, clinicians should not withhold CBT treatment for depression in patients with HIV and problematic substance use to attain reductions in depression and gains in adherence.


Heterophilic serum antibodies: a cause for falsely elevated serum thyrotropin levels.
We report two cases of euthyroid patients with inappropriately elevated serum levels of thyrotropin (TSH) in whom investigation led to the detection of heterophilic antibodies. In addition, we compare the performance of two TSH immunometric assay systems in this setting. Even when monoclonal assay systems are used, TSH results must be critically interpreted when they are at variance with clinical and other biochemical findings.


Herbaspirillum sp. strain GW103 alleviates salt stress in Brassica rapa L. ssp. pekinensis.
Mutual interactions between plant and rhizosphere bacteria facilitate plant growth and reduce risks of biotic and abiotic stresses. The present study demonstrates alleviation of salt stress in Brassica rapa L. ssp. perkinensis (Chinese cabbage) by Herbaspirillum sp. strain GW103 isolated from rhizosphere soil of Phragmites australis. The strain was capable of producing plant beneficial factors, such as auxin, siderophore, and 1-aminocylopropane-1-carboxylic acid deaminase. Treatment of strain GW103 on Chinese cabbage under salt stress increased K(+)/Na(+) ratio in roots generating balance in the ratio of ion homeostasis and consequently contributed to the increase of biomass. In addition, root colonization potential of the strain was observed by green fluorescent protein (GFP)-tagging approach. These results strongly suggest the beneficial impact of strain GW103 by inducing the alleviation of salt stress and development of stress tolerance in Chinese cabbage via plant-microbe interaction.


Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients.
Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated. There were 33 males and 25 females, with a mean age of 23.4 years. The main underlying disorders for which BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS hemorrhage was so extensive that it was considered to be the main cause of death. There was no significant statistical difference concerning sex (P = 0.217), age (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07), immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P = 0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing patients with or without ICH. However, the number of cases in which the CNS was defined as the main cause of death was higher among patients with ICH than in patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common and has a significant mortality rate following BMT.


Polyethylene glycol-based ultrasonic-assisted enzymatic extraction, characterization, and antioxidant activity in vitro and in vivo of polysaccharides from Lonicerae japonica leaves.
In this paper, polyethylene glycol (PEG)-based ultrasonic-assisted enzymatic extraction (UAEE) was employed in polysaccharides extraction from Lonicerae japonica leaves (LJLP). The optimal extraction conditions (extraction time of 33 min, PEG concentration of 30%, and ultrasonic power of 191 W) were obtained by Box-Behnken design (BBD). Under this condition, the LJLP yield was 14.76%. Furthermore, LJLP was identified as a typical heteropolysaccharide considering the main constitutive monosaccharides include galactose (32.3%), glucose (20.9%), and ribose (15.2%). Moreover, LJLP exhibited high total reducing power and considerable scavenging activities on superoxide radicals, in a concentration-dependent manner in vitro. In addition, antioxidant analysis in vivo revealed that for the LJLP-treated mice, the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, and total antioxidant capacity (TAOC) were significantly increased, while the level of malondialdehyde (MDA) was decreased in both serum and liver.


Benign Jaw Lesions.
There are both odontogenic and nonodontogenic benign lesions in the maxilla and mandible. These lesions may have similar imaging features, and the key radiographic features are presented to help the clinician narrow the differential diagnosis and plan patient treatment. Both intraoral and panoramic radiographs and advanced imaging features are useful in assessing the benign lesions of the jaws. The location, margins, internal contents, and effects of the lesions on adjacent structures are important features in diagnosing the lesions.


The Iron Henry: How One Sword Swallower Advanced Modern Medicine.
Sword swallowing is an ancient skill that was developed by the fakirs of India and slowly permeated the globe leading up to the late 19th century. Its rise as a popular circus act in Europe coincided with the surge of inventive young minds in the medical community. This crossroad brought about a working relationship between Dr Adolf Kussmaul and a sword swallower named the "Iron Henry." Together, they developed a scope that could be passed through the esophagus for evaluation of disease states from the upper aerodigestive tract all the way to the antrum of the stomach. The unique abilities refined by years of sword swallowing were vital in the work to develop and perform the first successful esophagoscopy and then disseminate the technology. This story should not be forgotten and can give insight into how historical practices and modern invention can come together to great effect.


Investigation of the induced-fit mechanism and catalytic activity of the human cytomegalovirus protease homodimer via molecular dynamics simulations.
Human cytomegalovirus (HCMV) is a highly species-specific DNA virus infecting up to 80% of the general population. The viral genome contains the open reading frame UL80, which encodes the full-length 80 kDa HCMV serine protease and its substrate. Full-length HCMV protease is composed of an N-terminal 256-amino-acid proteolytic domain, called assemblin, a linker region, and a C-terminal structural domain, the assembly protein precursor. Biochemical studies have shown that dimerization activates assemblin because of an induced stabilization of the oxyanion hole (Arg166). Thus, we performed here molecular dynamics (MD) simulations on HCMV protease models to study the induced-fit mechanism of the enzyme upon the binding of substrates and peptidyl inhibitors, and structural and energetic factors that are responsible for the catalytic activity of the enzyme dimer. Long and stable trajectories were obtained for the models of the monomeric and dimeric states, free in solution and bound to a peptidyl-activated carbonyl inhibitor, with very good agreement between theoretical and experimental results. Our results suggest that HCMV protease is indeed a novel example of serine protease that operates by an induced-fit mechanism. Also, in agreement with mutagenesis studies, our MD simulations suggest that the dimeric form is necessary to activate the enzyme because of an induced stabilization of the oxyanion hole.


The effect of shortening the preoperative fasting period on patient comfort and gastrointestinal function after elective laparoscopic surgery.
To explore the influence of shortening preoperative fasting on the comfort and gastrointestinal function of patients undergoing elective laparoscopic surgery. a total of 179 patients undergoing elective laparoscopic cholecystectomies (LC) in our hospital from March, 2019 to August, 2020 were recruited as the study cohort and placed into the research group (n=97) or the control group (n=82) according to different fasting periods assigned to each patient. In the control group, the patients were subjected to 12-h fasting and 6-h water deprivation before their surgeries, and the patients in the research group were subjected to 6-h fasting and 2-h water deprivation. The preoperative hunger and thirst, comfort, anxiety, and intraoperative aspiration, as well as the postoperative hospital stay durations, the blood glucose levels, the nausea and vomiting, the pain levels, and the times to the recovery of gastrointestinal function were compared between the two groups. The research group had shorter hospital stay durations and decreased blood glucose levels. No intraoperative aspiration occurred in either group, and the incidence of postoperative nausea and vomiting in the research group was lower than it was in control group. The patients in the research group were less hungry and thirsty and were more comfortable in the preoperative period, and their preoperative self-rating anxiety scale (SAS) and postoperative visual analog scale (VAS) scores were lower than the corresponding scores in the control group. The times to first oral feeding, ambulation, anal flatus, defecation, and bowel sounds in the research group were earlier than they were in the control group. Shortening preoperative fasting improves the comfort levels of patients undergoing elective LC, alleviates thirst and hunger, promotes the recovery of gastrointestinal function, and relieves preoperative anxiety, postoperative pain, and adverse reactions.


Prostate sarcoma.
This report is intended to provide insight into the presentation, diagnosis, and treatment of prostatic sarcomas. A literature review is included to compare variables in demographics, histology, prognosis, and treatment strategies among previously reported incidences. In this case, we have a 72-year-old man who initially presented with symptomatic nephrolithiasis that led to further workup. Magnetic resonance imaging revealed an enlarged, heterogeneous prostate with a dominant mass in the left lobe. A biopsy of the prostate revealed a high-grade, undifferentiated sarcoma in the left lobe along with concomitant adenocarcinoma in the right lobe. The patient underwent a radical prostatectomy, which according to existing literature remains the most effective treatment strategy. Staging is the most important prognostic indicator, making this cancer particularly dangerous as presenting symptoms are highly variable among patients.


Scan-Rescan Repeatability and Impact of B0 and B1 Field Nonuniformity Corrections in Single-Point Whole-Brain Macromolecular Proton Fraction Mapping.
Single-point macromolecular proton fraction (MPF) mapping is a recent quantitative MRI method for fast assessment of brain myelination. Information about reproducibility and sensitivity of MPF mapping to magnetic field nonuniformity is important for clinical applications. To assess scan-rescan repeatability and a value of B0 and B1 field inhomogeneity corrections in single-point synthetic-reference MPF mapping. Prospective. Eight healthy adult volunteers underwent two scans with 11.5 ± 2.3 months interval. 3T; whole-brain 3D MPF mapping protocol included three spoiled gradient-echo sequences providing T1 , proton density, and magnetization transfer contrasts with 1.25 × 1.25 × 1.25 mm3 resolution and B0 and B1 mapping sequences. MPF maps were reconstructed with B0 and B1 field nonuniformity correction, B0 - and B1 -only corrections, and without corrections. Mean MPF values were measured in automatically segmented white matter (WM) and gray matter (GM). Within-subject coefficient of variation (CV), intraclass correlation coefficient (ICC), Bland-Altman plots, and paired t-tests to assess scan-rescan repeatability. Repeated-measures analysis of variance (ANOVA) to compare field corrections. Maximal relative local MPF errors without correction in the areas of largest field nonuniformities were about 5% and 27% for B0 and B1 , respectively. The effect of B0 correction was insignificant for whole-brain WM (P > 0.25) and GM (P > 0.98) MPF. The absence of B1 correction caused a positive relative bias of 4-5% (P < 0.001) in both tissues. Scan-rescan agreement was similar for all field correction options with ICCs 0.80-0.81 for WM and 0.89-0.92 for GM. CVs were 1.6-1.7% for WM and 0.7-1.0% for GM. The single-point method enables high repeatability of MPF maps obtained with the same equipment. Correction of B0 inhomogeneity may be disregarded to shorten the examination time. B1 nonuniformity correction improves accuracy of MPF measurements at 3T. Reliability of whole-brain MPF measurements in WM and GM is not affected by B0 and B1 field corrections. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1789-1798.


Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.
Lung transplantation is effective for end-stage pulmonary disease, but its successful application is still limited by organ shortage and sub-optimal preservation techniques. Therefore, optimal allograft protection is essential to reduce organ dysfunction, especially in the early post-operative period. Intravenous prostanoids are routinely used to ameliorate reperfusion injury. However, the latest evidence suggests similar efficacy using inhaled prostacyclin. Thus, we evaluated the impact of donor pre-treatment using the prostacyclin analog, iloprost, on post-ischemic function of Perfadex-protected allografts. In Group 1, 5 pig lungs were preserved with Perfadex (PER group) solution and stored for 27 hours. In Group 2, 100 microg of iloprost was aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb) before identical organ harvest (PER-ILO group). After left lung transplantation and contralateral lung exclusion, hemodynamic variables, Po2/Fio2 and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry (W/D) weight ratio. Statistical assessment included analysis of variance (ANOVA) with repeated measures. Dynamic compliance and pulmonary vascular resistance (PVR) were superior in iloprost-treated compared with untreated organs (p < 0.05), whereas oxygenation was comparable between groups. W/D ratio revealed a significantly smaller amount of lung water in PER-ILO organs (p = 0.048), whereas stereologic data showed a trend toward less intra-alveolar edema. Endobronchial application of iloprost in donor lungs before Perfadex preservation decreases post-ischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.


Fixed subaortic stenosis: the value of cross-sectional echocardiography in evaluating different anatomical patterns.
We present a study using cross-sectional echocardiography in 39 patients (29 male and 10 female) with discrete subaortic stenosis. Five parameters were evaluated in the study: the morphology of the obstruction, the distance of the stenosis from the aortic valve, the type of insertion, the base of implantation, and any associated anomalies. The lesion could be divided into groups with either fibrous or fibromuscular shelves. In the group of 14 patients with fibrous shelves, the distances from the stenotic lesion to the aortic valve was less than 15% of the length of the left ventricle. The obstructive fibrous tissue was inserted on the septum and extended onto the aortic leaflet of the mitral valve (circumferential lesion) in 12 cases. The base of implantation was narrow in all 14 of them. In the 25 patients having fibromuscular lesions, the distance between obstruction and valve was greater than 18.4% of the length of the left ventricle. The insertion of the obstructive lesion was circumferential in 18 cases and its base of implantation was wide in 20 of the patients. Nineteen patients, 16 of whom had fibromuscular lesions, showed associated anomalies. Statistical analysis showed a good correlation between the type of stenosis and the base of implantation of the stenotic lesion (P less than 0.001) or associated anomalies (less than 0.01), but there was no distinction between the groups with regard to the type of insertion (less than 0.38). Twenty-five patients underwent surgical correction which was carried out between the ages of 4-14 years. Prosthetic valves (3 aortic and 1 mitral) were inserted in 4 patients.(ABSTRACT TRUNCATED AT 400 WORDS)


The COPD-readmission (CORE) score: A novel prediction model for one-year chronic obstructive pulmonary disease readmissions.
Acute exacerbation of chronic obstructive pulmonary disease (COPD) results in deterioration of lung function and mortality. Previous prediction models have been designed for severe exacerbation of COPD, leading to readmission. However, these models lacked newly established predictors such as the eosinophil count. The present study developed a novel CO PD-re admission (CORE) score. We retrospectively reviewed medical records of patients visiting Taipei Tzu Chi Hospital between January 1, 2014, and May 31, 2017. We analyzed all covariates by univariate and then multivariate logistic regressions. Numeric or ordinal variables showing statistical significance were transformed into dichotomous variables by cut-off values determined by the Youden Index. The CORE score was designed to predict one-year readmission rates. A total of 625 patients were recruited. After analysis, the CORE score included five predictors (eosinophil count, lung function, triple inhaler therapy, previous hospitalization, and neuromuscular disease). We observed a highly linear relationship between the CORE score and COPD readmission (R = 0.981; R 2 = 0.963; P < 0.001). The CORE score had a higher predictive accuracy than that for hospitalization in the previous year (area under the curve = 0.703 vs. 0.619; P < 0.001). Patients with higher CORE scores had a shorter time to first COPD readmission (P < 0.001). Using the zero point as a reference, the hazard ratios for each score from 1 to 4 were 1.209, 2.211, 3.359, and 4.510, respectively. The CORE score includes two novel predictors (eosinophil count and triple inhaler therapy). The model has a high predictive power for one-year COPD readmission.


The pattern of depressive symptoms in people with type 2 diabetes: a prospective community study.
The aim of the present study was to identify and describe longitudinal patterns of depression in a community sample of people with type 2 diabetes in Quebec, Canada. A prospective community based study in Quebec, Canada, was carried out between 2008 and 2011. Participants with diabetes were assessed at baseline and at 1, 2 and 3 years follow-up (n=1388). Depression was assessed using the patient health questionnaire (PHQ-9). Longitudinal latent class analysis yielded four clusters representing different longitudinal patterns of depression: cluster 1 ("no depression"; 67%): participants had neither minor nor major depression over time. Cluster 2 ("slowly increasing prevalence of minor and major depression over time"; 20%): participants had low levels of depression at baseline but increasing levels of minor and major depression over time; while most of the Cluster 3 ("increasing major depression"; 6%) participants had high and increasing levels of major depression over time. Participants in cluster 4 ("improved depression"; 7%) started with high levels of depression but progressed to low levels of depression. Our results provide important evidence of different longitudinal patterns of depression in people with type 2 diabetes. Identification of four distinct groups of participants might improve our understanding of the course of depression and may provide a basis of classification for intervention.


TNF-α is upregulated in T2DM patients with fracture and promotes the apoptosis of osteoblast cells in vitro in the presence of high glucose.
Fracture healing is regulated by proinflammatory mediators such as tumor necrosis factor-α (TNF-α), which poses influence on the balance between bone formation and remodeling. And the diabetes is thought to contribute to the delayed diabetic fracture healing. In the present study, we examined the promotion to proinflammatory cytokines and chemokines in type 2 diabetes mellitus (T2DM) patients with bone fractures, and then evaluated the promotion to TNF-α by the high glucose treatment in human osteoblast-like MG-63 cells and the regulatory role of the promoted TNF-α on the MG-63 cell apoptosis. It was demonstrated that there were significantly-upregulated high-sensitivity C-reactive protein (hsCRP) TNF-α, IL-1β, IL-6, IFN-γ-inducible protein 10 (IP-10) and RANTES in T2DM patients with bone fracture. And the promotion to TNF-α and IL-1β was confirmed in vitro in both mRNA and protein levels in high glucose-treated MG-63 cells. And either TNF-α or high glucose reduced the viability of MG-63 cells, promoted apoptosis and upregulated apoptosis-associated markers, such as released cytochrome c, cleaved caspase 3 and lyzed PARP. Moreover, there was a synergistic effect between TNF-α and high glucose. The viability reduction and the apoptosis induction of MG-63 cells were significantly higher in the group with both TNF-α and high glucose treatments, than in the group with singular TNF-α treatment. In conclusion, our study demonstrated that proinflammatory cytokines and chemokines were promoted in T2DM patients with bone fracture or in osteoblasts by the high glucose stimulation. TNF-α and high glucose synergistically reduced the viability and induced the apoptosis in the osteoblast-like MG-63 cells in vitro. It implies the significant regulatory role of TNF-α in the delayed fracture healing in T2DM.


Epidemiologic considerations in cardiovascular diseases in the elderly: international comparisons and trends.
As developed countries experience an "aging" of their populations, concern over cardiovascular disease, an important cause of death in the elderly, has grown. Improvements in the mortality rates of ischemic heart disease have been observed over the last 10 or 15 years in many nations, including Australia, the United States, Canada and Belgium. In other countries, mortality rates have remained unchanged and in some Eastern European countries, mortality rates have increased. In most instances where mortality rates have decreased, the reduction has been observed in both genders and has occurred across a wide age grouping, even in those aged 75 years and older. Truly representative data on risk factors for cardiovascular disease in the elderly are difficult to find; a new study has commenced in Australia and may provide more information.


[Reactions of the tectum neurons of the frog to movement into its field of vision of an object with different velocities].
Neurons with different "velocity selectiveness" and different "velocity sensitivity" were found in the frog midbrain tectum as well as neurons with different types of the firing rate dependence on the velocity of a visual stimulus motion. Visual recognition in frogs seems to proceed with the aid of two systems: the image--detecting and the image--describing those which complement each other.


Screening and application of a truncated aptamer for high-sensitive fluorescent detection of metronidazole.
Aptamer-based biosensors have been widely constructed and applied to detect diverse targets. Metronidazole is a widely used broad-spectrum antibacterial drug, whose residue has multiple risks to human health. Herein, metronidazole-specific aptamers were selected from a random ssDNA library with the full length of 79 nucleotides (nt) based on DNA library-immobilized magnetic beads SELEX technology. After ten rounds of selection, four aptamers with highly similar secondary structures were selected, among which AP32, with the lowest dissociation constants, was chosen as the optimal aptamer for further optimization. Then a semi-rational post-SELEX truncation was carried out based on the secondary structure analysis and molecular docking, as well as affinity assessment. Redundant nucleotides in AP32 were stepwise removed without the decrease of affinity. Following such strategy, a truncated aptamer AP32-4 with the length of only 15 nt was eventually screened. The dissociation constant of 77.22 ± 11.27 nM is almost equivalent to the original AP32. Furthermore, an aptamer-based fluorescent biosensor for metronidazole was constructed based on AP32-4. With the help of exonuclease-assisted target-recycling amplification, the biosensor exhibits a linear detection range of 25-800 nM, and the detection limit of 10.50 nM. The biosensor was applied to detect metronidazole in honey samples. The results show that not only an efficient strategy for screening robust and practicable aptamers, but also an ultrahigh sensitive detection platform for metronidazole were established.