Patterns of burn injury in the preambulatory infant.
This study was undertaken after an increasing trend in young babies presenting with severe burns was observed in Princess Margaret Hospital (PMH) in Perth, Western Australia. The aim was to explore the patterns of these injuries with a view to identifying whether they could be prevented with better parent education. Inclusion criteria was infants under 6 months of age who sustained a burns injury requiring admission or out-patient treatment in the Burns Unit of PMH between July 2005 and September 2007. Immobile infants are at significant risk of burns. In infants who are not yet mobile, environmental factors are commonly implicated, with the vast majority of burns sustained in the home. The mechanisms of injuries were scalds (43%), contact burns (39%), sunburn (11%) and TPN burns in premature infants in NICU (7%). TBSA ranged from <0.5% to 30%. Infants less than 6-month-old are at significant risk of burn; at this age the injury is usually caused by hazards in the home environment. These infants are vulnerable to inadequate first aid and require a large amount of follow-up care. Better parental education may help reduce the number of injuries we see in this age group.


Heterogeneous Dolichos biflorus lectin binding to a subset of rat alveolar macrophages in normal and fibrotic lung tissue.
The distribution of Dolichos biflorus lectin in the rat lung and during fibrosis after irradiation was investigated by lectin histochemical and electron microscopical techniques and double immunofluorescence labelling with the monoclonal antibodies RM-1 and ED-1. The results indicate a selective reaction of Dolichos biflorus lectin with a subpopulation of alveolar macrophages. No binding of the lectin was detectable in ED-1-positive macrophages but strong staining occurred in a part of the RM-1-positive cell population. In fibrotic lung specimens an increased number of Dolichos biflorus lectin-positive macrophages was found in which focally ED-1 reactive and RM-1 negative cells appeared. The finding of changing lectin binding pattern in a radiation-induced lung model emphasizes the suitability of the Dolichos biflorus lectin as a marker of macrophage activation or functional specialization.


Effects of short- and long-term feeding of zinc oxide-supplemented diets on the mature, female domestic fowl with special reference to tissue mineral content.
1. In Expt 1, the effects on laying hens of diets supplemented with zinc oxide providing up to 20 g added zinc/kg were compared. In Expt 2 the diets contained up to 6 g added Zn/kg. 2. In both experiments, food intake, body-weight, egg number, and liver, oviduct and ovary weights/kg body-weight were significantly reduced by added ZnO; gizzard weight/kg body-weight was significantly increased. In Expt 2, pancreas weight was significantly reduced by added ZnO. 3. Liver, kidney and pancreatic Zn and iron concentrations were significantly elevated in both experiments. 4. In both experiments, liver, kidneys and pancreatic copper concentrations gave quadratic responses to added ZnO.


Neuroimaging and neuropathology studies of X-linked dystonia parkinsonism.
X-linked Dystonia Parkinsonism (XDP) is a recessive, genetically inherited neurodegenerative disorder endemic to Panay Island in the Philippines. Clinical symptoms include the initial appearance of dystonia, followed by parkinsonian traits after 10-15 years. The basal ganglia, particularly the striatum, is an area of focus in XDP neuropathology research, as the striatum shows marked atrophy that correlates with disease progression. Thus, XDP shares features of Parkinson's disease symptomatology, in addition to the genetic predisposition and presence of striatal atrophy resembling Huntington's disease. However, further research is required to reveal the detailed pathology and indicators of disease in the XDP brain. First, there are limited neuropathological studies that have investigated neuronal changes and neuroinflammation in the XDP brain. However, multiple neuroimaging studies on XDP patients provide clues to other affected brain regions. Furthermore, molecular pathological studies have elucidated that the main genetic cause of XDP is in the TAF-1 gene, but how this mutation relates to XDP neuropathology still remains to be fully investigated. Hence, we aim to provide an extensive overview of the current literature describing neuropathological changes within the XDP brain, and discuss future research avenues, which will provide a better understanding of XDP neuropathogenesis.


Translation of evidence into kidney transplant clinical practice: managing drug-lab interactions by a context-aware clinical decision support system.
Drug-laboratory (lab) interactions (DLIs) are a common source of preventable medication errors. Clinical decision support systems (CDSSs) are promising tools to decrease such errors by improving prescription quality in terms of lab values. However, alert fatigue counteracts their impact. We aimed to develop a novel user-friendly, evidence-based, clinical context-aware CDSS to alert nephrologists about DLIs clinically important lab values in prescriptions of kidney recipients. For the most frequently prescribed medications identified by a prospective cross-sectional study in a kidney transplant clinic, DLI-rules were extracted using main pharmacology references and clinical inputs from clinicians. A CDSS was then developed linking a computerized prescription system and lab records. The system performance was tested using data of both fictitious and real patients. The "Questionnaire for User Interface Satisfaction" was used to measure user satisfaction of the human-computer interface. Among 27 study medications, 17 needed adjustments regarding renal function, 15 required considerations based on hepatic function, 8 had drug-pregnancy interactions, and 13 required baselines or follow-up lab monitoring. Using IF & THEN rules and the contents of associated alert, a DLI-alerting CDSS was designed. To avoid alert fatigue, the alert appearance was considered as interruptive only when medications with serious risks were contraindicated or needed to be discontinued or adjusted. Other alerts appeared in a non-interruptive mode with visual clues on the prescription window for easy, intuitive notice. When the system was used for real 100 patients, it correctly detected 260 DLIs and displayed 249 monitoring, seven hepatic, four pregnancy, and none renal alerts. The system delivered patient-specific recommendations based on individual lab values in real-time. Clinicians were highly satisfied with the usability of the system. To our knowledge, this is the first study of a comprehensive DLI-CDSS for kidney transplant care. By alerting on considerations in renal and hepatic dysfunctions, maternal and fetal toxicity, or required lab monitoring, this system can potentially improve medication safety in kidney recipients. Our experience provides a strong foundation for designing specialized systems to promote individualized transplant follow-up care.


The Dust Bowl in the US: An Analysis Based on Current Environmental and Clinical Studies.
The Dust Bowl occurred in the Central Plains states in the United States between 1930 and 1940. Prolonged drought, intense recurrent dust storms and economic depression had profound effects on human welfare. The causes included increased farming on marginal land, poor land management, and prolonged drought. There was a significant increase in the number of cases of measles, increased hospitalization for respiratory disorders and increased infant and overall mortality in Kansas during the Dust Bowl. Recent scientific studies have demonstrated that dust transmits measles virus, influenza virus and Coccidioides immitis, and that mortality in the United States increases following dust storms with 2-3-day lag periods. Advances in technology have provided information about the composition of dust and the transfer of microbial pathogens in dust and provided the framework for reducing the economic and health consequences of the next prolonged drought in the United States.


A novel sucrose hydrolase from the bombycoid silkworms Bombyx mori, Trilocha varians, and Samia cynthia ricini with a substrate specificity for sucrose.
Although membrane-associated sucrase activity has been detected in the midgut of various lepidopteran species, it has not yet been identified and characterized at the molecular level. In the present study, we identified a novel sucrose hydrolase (SUH) gene from the following three bombycoid silkworms: Bombyx mori, Trilocha varians, and Samia cynthia ricini and named them BmSuh, TvSuh, and ScSuh, respectively. The EST dataset showed that BmSuh is one of the major glycoside hydrolase genes in the larval midgut of B. mori. These genes were almost exclusively expressed in the larval midgut in all three species, mainly at the feeding stage. SUHs are classified into the glycoside hydrolase family 13 and show significant homology to insect maltases. Enzymatic assays revealed that recombinant SUHs were distinct from conventional maltases and exhibited substrate specificity for sucrose. The recombinant BmSUH was less sensitive to sugar-mimic alkaloids than TvSUH and ScSUH, which may explain the reason why the sucrase activity in the B. mori midgut was less affected by the sugar-mimic alkaloids derived from mulberry.


Stress proteins of Clostridium perfringens type A immunoreact with antiserum from rabbits infected with gas gangrene.
Various stressors were used to induce stress proteins in Clostridium perfringens. Cultures of C. perfringens FD-1041 were subjected to cold shock (28 degrees C for 1 h), acid shock (pH 4.5 for 30 min), or heat shock (50 degrees C for 30 min). Cells were lysed and protein samples were analyzed by immunoblotting with antiserum derived from rabbits suffering from gas gangrene. Eight cold shock proteins (approximate Mr 101, 82, 70, 37, 22, 12, 10 and 6 kDa) and also eight heat shock proteins (approximate Mr 101, 82, 70, 27, 22, 16, 12 and 10 kDa) were immunoreactive with the serum. No immunoreactive proteins were detected in samples subjected to acid shock proteins and purified DnaK protein was also non-immunoreactive with the serum. These immunogenic stress proteins may be important in regulating diseases caused by C. perfringens. Such proteins could be involved in cell survival mechanisms, serve as targets during infection, or play a role in recognition of the bacteria by the host.


Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and testicular injuries in male mice.
Toxic heavy metals in water, air and soil are global problems that are a growing threat to humanity. Heavy metals are widely distributed in the environment and some of them occur in food, water, air and tissues even in the absence of occupational exposure. The antioxidant and protective influences of vitamin E on a mixture of some heavy metals (Pb, Hg, Cd and Cu)-induced oxidative stress and renal and testicular injuries were evaluated in male mice. Exposure of mice to these heavy metals in drinking water for seven weeks resulted in statistical increases of plasma creatinine, urea and uric acid concentrations. The levels of glutathione (GSH) and superoxide dismutases (SOD) in kidney and testis tissues were significantly declined. Moreover, the histopathological evaluation of kidney and testis showed severe changes in mice treated with these heavy metals. Administration of vitamin E protected the kidney and testis of mice exposed to heavy metals as evidenced by appearance of normal histological structures, insignificant changes in the values of plasma creatinine, urea and uric acid, and the levels of kidney GSH and SOD, while the levels of testis GSH and SOD were notably decreased. These data suggest that the administration of vitamin E protects against heavy metals-induced renal and testicular oxidative stress and injuries.


Cardenolide analogs. An explanation for the usual properties of AY 22241.
AY 22241 (AY) was compared with digitoxigenin with respect to effects on myocardial contractility and inhibition of Na+, K+-ATPase. Ay was less potent than digitoxigenin but otherwise showed the same type of rapid onset and rapid reversal of activity usually associated with genins. Since AY is a glycoside, its behaviour was regarded as anomalous since glycosides usually show both slow onset and slow reversal of activity. Attempts were made to account for the genin-like properties of AY in terms of the model for the digitalis receptor proposed by Thomas et al. (1974a,b). It is suggested that the low potency and genin-like properties of AY may be due to the fact that the steroid is attached to the lactone through the carbon atom that is alpha to the carbonyl group. This feature could result in non-alignment of the sugar residue with the sugar binding site and might also reduce the effectiveness of the interaction of the steroid moiety with its binding site. A notable feature of AY toxicity was its extremely rapid progression to irreversible fibrillation.


Comparison of early postoperative quality of life in minimally invasive versus conventional valve surgery.
Minimally invasive cardiac surgery (MICS), an approach in which full sternotomy is avoided and the surgical incision is minimal, has been shown to produce less postoperative discomfort and to enable earlier mobilization and discharge than conventional cardiac surgery (CCS). This study was performed to retrospectively evaluate quality of life following MICS in comparison with CCS valve surgery. Sixty-six patients scheduled for MICS and 50 patients scheduled for CCS for isolated aortic or mitral valve surgery from January 1999 to June 2001 were enrolled in the study. The clinical records for the two groups were compared across intraoperative parameters and those associated with postoperative quality of life. The aortic clamp and cardiopulmonary bypass times in the MICS group were longer than those in the CCS group (144 +/- 42 and 224 +/- 58min vs 112 +/- 21 and 179 +/- 27min, P < 0.001). Postoperative pain medication (rectal buprenorphine and intramuscular pethidine) was administered to 18 of the 66 MICS patients (27%), as compared with 26 of the 50 CCS patients (52%, P = 0.007). Postoperative delirium was less frequent in the MICS group than the CCS group (26% vs 44%, P = 0.039). Initial postoperative food intake and urine catheter removal were possible earlier in the MICS than in the CCS group. MICS patients had shorter stays in the intensive care unit than CCS patients (37.4 +/- 7.3 vs 45.9 +/- 8.7h, P < 0.001). Although longer aortic clamp and cardiopulmonary bypass times remain a problem in MICS procedures, our results suggest that MICS, as compared with CCS, facilitates earlier recovery of daily activities and provides improved quality of life in the early postoperative period.


Effect of interferon on 5-fluorouracil-induced perturbations in pools of deoxynucleotide triphosphates and DNA strand breaks.
Interferon (IFN) augments the anabolism of 5-fluorouracil (5FU) to its active metabolite, fluorodeoxyuridylate (FdUMP), which inhibits thymidylate synthase (TS). We sought to determine whether this resulted in greater perturbations of nucleotide pools and if so, whether this was associated with an increase in cell lethality, specifically focussing on the lethal cellular lesion, DNA double strand breaks (dsb). To determine whether combination therapy with 5FU + IFN resulted in greater depletion of thymidine nucleotide pools than 5FU alone, a highly sensitive DNA polymerase assay was used. In two human colon cancer cell lines, treatment with 5FU + IFN resulted in a rapid decrease in levels of dTTP by 95%. The addition of IFN to 5FU resulted in greater depletion of dTTP levels over treatment with 5FU alone by up to fourfold, and markedly augmented the dATP/dTTP ratio. The addition of IFN to 5FU had no effect on 5FU-induced perturbations in dCTP, dGTP or dATP pools at 8 and 12 h. Measurement of DNA dsb demonstrated that treatment of HT-29 cells with 10 microM 5FU for 24 h did not increase DNA dsb versus control. The combination of 5FU + 500 U/ml IFN, however, resulted in an increased number of dsb versus both 5FU and untreated control cells (P < 0.01), equivalent to 0.74 +/- 0.12 Gy. The addition of IFN to 5FU resulted in a selective further depletion of pools of dTTP and an increase in the number of DNA dsb versus 5FU treatment alone.


The rotenone model of Parkinson's disease: genes, environment and mitochondria.
Parkinson's disease (PD) is occasionally caused by single gene mutations or by single toxic exposures, but most cases of PD are probably caused by some combination of genetic susceptibility and environmental exposure. Using rotenone as a prototype for an environmental toxicant, we argue here that genetic and environmental causes of PD converge on common pathogenic mechanisms. If so, protective strategies devised for one type of PD may be broadly useful for other forms of the disease.


The effects of probiotic supplementation on the gene expressions of immune cell surface markers and levels of antibodies and pro-inflammatory cytokines in human milk.
This study investigated the impact of probiotic supplementation on the gene expressions of cluster of differentiation (CD) as cell markers and the concentrations of antibodies and cytokines in human milk. Gene expressions of CD28, CD19, and CD38 were determined in milk from 15 women ingesting daily probiotics (from Greek yogurt) and 12 women who do not consume probiotics. Concentrations of antibodies and cytokines were measured using ELISA. Gene expression of CD28 tended to be higher in milk from mothers ingesting daily probiotics than mothers who did not take probiotics. Interleukin-6 (IL-6) concentration in milk was higher in mothers ingesting probiotics than those who do not consume probiotics. The increase of IL-6 level in human milk was positively correlated with total IgA and IgG concentrations. Probiotic supplementation could enhance the secretion of IL-6 in human milk. Human milk IL-6 may improve neonatal immunity due to its stimulation of total IgA and IgG.


Whey protein improves the stability of C-phycocyanin in acidified conditions during light storage.
C-phycocyanin is a bright blue natural colorant used in food and beverage applications. However, its color stability is poor in acidic conditions under exposure to light. In this work, we study the use of whey protein isolate (WPI) to protect C-phycocyanin from color degradation. Low concentration (0.05-0.1%) WPI addition delayed (~2 days) the color degradation of C-phycocyanin at pH 3.0 over 5-day storage in light. However, the color degradation was aggravated adversely during 5-day light storage when C-phycocyanin mixed with a higher concentration (~1%) of WPI degraded after heat-treatment. The Fourier transform infrared and fluorescence spectroscopy confirmed that structural changes (e.g., alpha-helix protection and transformation from alpha-helix to beta-sheet) of C-phycocyanin due to interaction with WPI. These results, along with quartz crystal microbalance with dissipation technology outcomes, suggest that a low concentration of WPI may help protect C-phycocyanin's secondary structure from becoming damaged during light storage, preventing its color degradation.


Physiological roles of animal succinate thiokinases. Specific association of the guanine nucleotide-linked enzyme with haem biosynthesis.
The discovery of two distinct succinate thiokinases in mammalian tissues, one (G-STK) specific for GDP/GTP and the other (A-STK) for ADP/ATP, poses the question of their differential metabolic roles. Evidence has suggested that the A-STK functions in the citric acid cycle in the direction of succinyl-CoA breakdown (and ATP formation) whereas one role of the G-STK appears to be the re-cycling of succinate to succinyl-CoA (at the expense of GTP) for the purpose of ketone body activation. A third metabolic participation of succinyl-CoA is in haem biosynthesis. This communication shows that in chemically induced hepatic porphyria, when the demand for succinyl-CoA is increased, it is the level of G-STK only which is elevated, that of A-STK being unaffected. The results implicate G-STK in the provision of succinyl-CoA for haem biosynthesis, a conclusion which is further supported by the observation of a high G-STK/A-STK ratio in bone marrow.


Removal of both anionic and cationic dyes from wastewater using pH-responsive adsorbents of L-lysine molecular-grafted cellulose porous foams.
High adsorption efficiency, active to both anionic and cationic dyes and simple desorption are three main challenges of the existed adsorbents for decolorization of the dye-contained wastewaters. Porous foams based on L-lysine (Lys) molecular-grafted cellulose were firstly designed and fabricated to overcome those challenges. Cellulose were grafted with Lys in 1-butyl-3-methylimidazolium chloride (BMIMCl) via a chemical connection resulted from glycidyl methacrylate (GMA). The synthesized cellulose derivative (Cell-g-PGMA-Lys) was regenerated in the morphology of foam by non-solvent induced phase inversion from the BMIMCl-based solutions. The presence of Lys moieties and porous structure of Cell-g-PGMA-Lys were confirmed with a series of instrumental analysis. Both anionic reactive brilliant red X-3B (RBR X-3B) and cationic methylene blue (MB) were effectively adsorbed on and desorbed from Cell-g-PGMA-Lys by adjusting the solution pH value. Cell-g-PGMA-Lys had higher adsorption capacities than most of the reported adsorbents and was easy to separate from the decolorized water. It could be reused many times with little reduction of the adsorption capacity, which remained 86.9% and 92.5% for RBR X-3B and MB respectively after six adsorption-desorption cycles. The isothermal and kinetic adsorption proved that dyes were adsorbed single-layered on Cell-g-PGMA-Lys depending upon the electrostatic interaction between adsorbent and adsorbate.


Preliminary evaluation of the performance of a new, highly sensitive commercial immunoassay for serum ferritin determination.
We evaluated the analytical performance of a new, commercial, fully automated immunoturbidimetric assay for the determination of ferritin [FER-Latex(X2)CN SEIKEN, Denka Seiken, Japan] in serum on the Olympus AU2700 analyzer. The new assay is a latex-enhanced turbidimetric immunoassay with an analysis time of 10 min. The linearity of the assay was confirmed up to 2505 pmol/L (R2=0.999). The detection limit and the functional sensitivity were both 4.5 pmol/L. The intra- and inter-assay imprecision (CV) at 67, 506, 2186 pmol/L was < 1.8% and < 2.5%, respectively. Verification of the traceability to a WHO standard (80/578) showed a recovery of 102.6% (target value 449 pmol/L). No hook effect was observed in samples containing up to 33,705 pmol/L. The assay showed good correlation with the Beckman Immage nephelometric system (r=0.999). Hemoglobin (< or = 9.8 g/L), total bilirubin (< or = 113 micromol/L), conjugated bilirubin (< or = 109 micromol/L) and rheumatoid factor (< or = 5.2x10(5) IU/L) did not interfere with the assay. The reference interval (2.5-97.5 percentile) was 72-521 pmol/L for men and 27-267 pmol/L for women. The reference interval in patients with anemia, malignant tumors and hemochromatosis was 5.6-52, 130-2436 and 1465-2903 pmol/L, respectively. On the basis of the receiver operating characteristic curve, the 90% sensitivity cut-off value to distinguish between patients with and without iron deficiency was 40 pmol/L. The new latex turbidimetric procedure for ferritin assay is an attractive alternative that avoids the need for dedicated instrumentation.


Integrated bioprocess for the production and purification of recombinant proteins by affinity chromatography in Escherichia coli.
In order to improve the effectiveness of the production of recombinant proteins in E. coli, integrated fermentation processes were developed. Therefore, expression vectors were constructed containing a strongly expressed gene for a beta-glucanase fused with a metal-chelating affinity tag and a leader peptide for directing the fusion protein into the periplasmic space. Its export into the medium was achieved by means of co-expression of a bacteriocin-release protein, the Kil protein from pColE1. Bioreactors were modified so that special devices containing metal chelate pentadentate chelator PDC resins were located within the bioreactor. Using the bioreactor with an internal device the Zn2+-PDC had a 4.3-fold higher binding capacity than metal-free PDC (12.3 and 2.6 kU ml(-1) PDC, respectively. Using the bioreactor with charged PDC in an external circuit revealed even higher beta-glucanase concentration (65.6 kU ml(-1)), i.e. 1.5-fold compared to the internal adsorbent system.


Bacterial lectin BambL acts as a B cell superantigen.
B cell superantigens crosslink conserved domains of B cell receptors (BCRs) and cause dysregulated, polyclonal B cell activation irrespective of normal BCR-antigen complementarity. The cells typically succumb to activation-induced cell death, which can impede the adaptive immune response and favor infection. In the present study, we demonstrate that the fucose-binding lectin of Burkholderia ambifaria, BambL, bears functional resemblance to B cell superantigens. By engaging surface glycans, the bacterial lectin activated human peripheral blood B cells, which manifested in the surface expression of CD69, CD54 and CD86 but became increasingly cytotoxic at higher concentrations. The effects were sensitive to BCR pathway inhibitors and excess fucose, which corroborates a glycan-driven mode of action. Interactome analyses in a model cell line suggest BambL binds directly to glycans of the BCR and regulatory coreceptors. In vitro, BambL triggered BCR signaling and induced CD19 internalization and degradation. Owing to the lectin's six binding sites, we propose a BCR activation model in which BambL functions as a clustering hub for receptor glycans, modulates normal BCR regulation, and induces cell death through exhaustive activation.


The bibliometric analysis and review of dioxin in waste incineration and steel sintering.
Facing the common treatment problems of dioxin whose major sources come from waste incineration and steel sintering, we handled a massive literature dataset from the Web of Science database and analyzed the research hotspot and development trend in this field in the past 40 years by bibliometric method. The result indicates that the field of dioxins generated from waste incineration and steel sintering has entered a stage of rapid development since 1990. China occupies a leading position in terms of comprehensive strength with the largest publications output as well as a greater influence in recent years. The most productive institutions and journals are Zhejiang University and Chemosphere, respectively. In addition, the most commonly used keywords in statistical analysis are "fly ash," "emission control," "risk assessment," "congener profile," "formation mechanisms," "sources," "catalysis," and "inhibition," which reflects the current main research direction in this field. The similarities and differences of dioxins generated in waste incineration and steel sintering are reviewed in this paper, which will provide guidance for the future research.


Isolation and characterization of a cDNA encoding the putative distal colon H+,K(+)-ATPase. Similarity of deduced amino acid sequence to gastric H+,K(+)-ATPase and Na+,K(+)-ATPase and mRNA expression in distal colon, kidney, and uterus.
A series of Northern blot hybridization experiments using probes derived from the rat gastric H+,K(+)-ATPase cDNA and the human ATP1AL1 gene revealed the presence of a 4.3-kilobase mRNA in colon that seemed likely to encode the distal colon H+,K(+)-ATPase, the enzyme responsible for K+ absorption in mammalian colon. A rat colon library was then screened using a probe from the ATP1AL1 gene, and cDNAs containing the entire coding sequence of a new P-type ATPase were isolated and characterized. The deduced polypeptide is 1036 amino acids in length and has an Mr of 114,842. The protein exhibits 63% amino acid identity to the gastric H+,K(+)-ATPase alpha-subunit and 63% identity to the three Na+,K(+)-ATPase alpha-subunit isoforms, consistent with the possibility that it is a K(+)-transporting ATPase. Northern blot analyses show that the 4.3-kilobase mRNA is expressed at high levels in distal colon; at much lower levels in proximal colon, kidney, and uterus; and at trace levels in heart and forestomach. The high mRNA levels in distal colon and the similarity of the colon pump to both gastric H+,K(+)- and Na+,K(+)-ATPases suggest that it is the distal colon H+,K(+)-ATPase. Furthermore, expression of its mRNA in kidney raises the possibility that the enzyme also corresponds to the H+,K(+)-ATPase that seems to play a role in K+ absorption and H+ secretion in the distal nephron.


Discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists with anti-psoriasis activity in a mouse model.
Aryl hydrocarbon receptor (AHR) is a ligand dependent transcription factor and participates in the regulation of the immune balance of Th17/22 and Treg cells. It has been found to be widely expressed in the skin, and involved in the pathology of psoriasis. Therefore, AHR is thought as a potential intervention target for psoriasis. Here, we report the discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists. Structure-activity relationship analyses led to the identification of the most active compound, 5- ((1H-indazol-3-yl)methylene) -3- (prop-2-yn-1-yl) -2-thiooimidazolidin-4-one (24e), which exhibited an EC50 value of 0.015 µM against AHR. Mechanism of action studies showed that 24e regulated the expression of CYP1A1 by activating the AHR pathway. Topical administration of 24e substantially alleviated imiquimod (IMQ)-induced psoriasis-like skin lesion. Overall, compound 24e could be a good lead compound for drug discovery against psoriasis, and hence deserving further in-depth studies.


New high-frequency catheter technique for His bundle ablation in dogs.
A new method is presented for the production of complete atrioventricular heart block. It consists of a special catheter, which is inserted into the right atrium via a femoral vein and positioned in the region of the His bundle for His bundle potential recording. Production of heart block is achieved by a high frequency current pulse from an electrocautery unit.


Resistance to gentamicin, tobramycin and amikacin among clinical isolates of bacteria.
Susceptibility to the administration of gentamicin, tobramycin and amikacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4,114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 microng discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 60%. Most of the gentamicin-resistant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnitude (most had minimal inhibitory concentrations (MIC's) between 31 and 125 microng/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.


Brain-wide dendrites in a near-optimal performance of dynamic range and information transmission.
Dendrites receive and process signals from other neurons. The range of signal intensities that can be robustly distinguished by dendrites is quantified by the dynamic range. We investigate the dynamic range and information transmission efficiency of dendrites in relation to dendritic morphology. We model dendrites in a neuron as multiple excitable binary trees connected to the soma where each node in a tree can be excited by external stimulus or by receiving signals transmitted from adjacent excited nodes. It has been known that larger dendritic trees have a higher dynamic range. We show that for dendritic tress of the same number of nodes, the dynamic range increases with the number of somatic branches and decreases with the asymmetry of dendrites, and the information transmission is more efficient for dendrites with more somatic branches. Moreover, our simulated data suggest that there is an exponential association (decay resp.) of overall relative energy consumption (dynamic range resp.) in relation to the number of somatic branches. This indicates that further increasing the number of somatic branches (e.g. beyond 10 somatic branches) has limited ability to improve the transmission efficiency. With brain-wide neuron digital reconstructions of the pyramidal cells, 90% of neurons have no more than 10 dendrites. These suggest that actual brain-wide dendritic morphology is near optimal in terms of both dynamic range and information transmission.


Membrane-dependent guanine nucleotide binding and GTPase activities of soluble protein from bovine rod cell outer segments.
Soluble proteins can be extracted by osmotic shock of purified rod (photoreceptor cell) outer segments that have intact plasma membranes. The soluble proteins include a component that contains tightly bound GDP-Exchange of this GDP with exogenous nucleotide is catalyzed by (and requires) the membranes from the outer segments. ATP does not participate in these reactions. Approximately one-half of the binding sites in the soluble component require GTP as the source of exogenous nucleotide; the remainder accept GTP or GDP with equal facility. When exogenous GTP is the source of bound nucleotide, it is found in the complex in the form of GDP. Exchange of bound nucleotide with GTP is stoichiometrically related to GTPase activity; this activity is highly dependent upon the presence of both membranes and soluble protein. The soluble nucleotide binding protein was purified by making use of the fact that it binds tightly to the membranes (under conditions of moderate ionic strength) in the absence of GTP and can be eluted by solutions containing low concentrations of GTP (but not GDP or ATP, nor can it be eluted by GTP-free solutions of low ionic strength). The purified protein contains two polypeptide chains of molecular weights 41,000 and 37,000; these are the major species that can be extracted from the outer segments by osmotic shock, and they constitute approximately 7% of the total protein of the isolated organelle.


Proteogenomic characterization of ferroptosis regulators reveals therapeutic potential in glioblastoma.
Ferroptosis is iron-dependent non-apoptotic cell death, that is characterized by the excessive accumulation of lipid peroxides. Ferroptosis-inducing therapy also shows promise in the treatment of cancers. However, ferroptosis-inducing therapy for glioblastoma multiforme (GBM) is still in the exploratory stage. We identified the differentially expressed ferroptosis regulators using Mann-Whitney U test in the proteome data from Clinical Proteomic Tumor Analysis Consortium (CPTAC). We next analyzed the effect of mutation on protein abundance. A multivariate Cox model was constructed to identify the prognostic signature. In this study, we systemically portrayed the proteogenomic landscape of ferroptosis regulators in GBM. We observed that some mutation-specific ferroptosis regulators, such as down-regulated ACSL4 in EGFR-mutated patients and up-regulated FADS2 in IDH1-mutated patients, were linked to the inhibited ferroptosis activity in GBM. To interrogate the valuable treatment targets, we performed the survival analysis and identified five ferroptosis regulators (ACSL3, HSPB1, ELAVL1, IL33, and GPX4) as the prognostic biomarkers. We also validated their efficiency in external validation cohorts. Notably, we found overexpressed protein and phosphorylation abundances of HSPB1 were poor prognosis markers for overall survival of GBM to inhibit ferroptosis activity. Alternatively, HSPB1 showed a significant association with macrophage infiltration levels. Macrophage-secreted SPP1 could be a potential activator for HSPB1 in glioma cells. Finally, we recognized that ipatasertib, a novel pan-Akt inhibitor, could be a potential drug for suppressing HSPB1 phosphorylation, inducing ferroptosis of glioma cells. In summary, our study characterized the proteogenomic landscape of ferroptosis regulators and identified that HSPB1 could be a candidate target for ferroptosis-inducing therapy strategy for GBM.


Midplane dose determination during total body irradiation using in vivo dosimetry.
During TBI techniques an accurate determination of the dose distribution is very difficult when using commercial treatment planning systems. In order to determine the midplane dose, an algorithm was developed based on the use of in vivo dosimetry. Scanditronix EDP-30 diodes were placed at the entrance and the exit surface for in vivo dosimetry. The proposed algorithm was validated firstly in a regular and homogeneous phantom of different thickness with an ionization chamber and TL dosimeters and secondly in an Alderson anthropomorphic phantom with TL dosimeters. In this study, in vivo measurements were evaluated in 60 patients and furthermore, in 20 of them, the midplane dose calculated with this algorithm was compared with the method described by Rizzotti A, Compri C, Garusi GF. Dose evaluation to patients irradiated by 60Co beams, by means of direct measurement on the incident and on the exit surfaces. Radiother. Oncol. 1985;3:279-283. No differences were found between the two methods. The differences between dose values calculated with both methods and dose values measured with the ionization chamber and TL dosimeters were within +/-22% and +/-4%, respectively, in the regular and homogeneous phantom and within +/-2% in the Alderson phantom. The algorithm was useful in calculating the midplane dose when heterogeneities as lungs were present. Even when partial transmission blocks were used to reduce the dose to the lungs, the algorithm with modified correction factors gave a midplane lung dose in the Alderson phantom within 1.3% of the measurements with TL dosimeters. For 360 patients' measurements in each A-P and P-A field, the relative deviations were analyzed between the measured and calculated entrance, exit dose and midplane dose and the prescribed dose, always applying the temperature correction factor. These deviations at the entrance dose were within +/-4%. Greater deviations were found for the exit dose measurements. Deviations larger than +/-10% corresponded in general to obese patients, with a thickness over 25 cm. The relative deviations between the total received and prescribed midplane doses in 60 patients were within +/-3%. The results indicate excellent correspondence between the total prescribed and calculated midplane doses using this algorithm while also no significant differences were found when the Rizzotti method was used. Comparison between doses measured with TL dosimeters in the core of Alderson phantom lungs and doses calculated from in vivo measurements showed that the proposed algorithm could be used in the presence of heterogeneities even when partial transmission blocks were used. The temperature correction factor must be applied in order to avoid a 2-3% dose overestimation.


Neuronal cell injury in patients after cardiopulmonary resuscitation: evaluation by diffusion-weighted imaging and magnetic resonance spectroscopy.
Neuronal cell injury after global cerebral ischemic insult is not well understood in humans. We performed serial examination of diffusion-weighted imaging and magnetic resonance spectroscopy in three patients after cardiopulmonary resuscitation. The presence of the signal for lactate in magnetic resonance spectroscopy in the acute stage after cardiopulmonary resuscitation was closely correlated to irreversible damage. In addition, high intensity in diffusion-weighted magnetic resonance image in the acute stage also predicted a poor outcome. Lesions that were positive for these factors in the acute stage led to serious brain damage in the subacute and chronic stages. The results indicated that after cardiopulmonary resuscitation, diffusion-weighted magnetic resonance imaging and magnetic resonance spectroscopy is an extremely useful modality to estimate the prognosis of patients, which is not always easy using conventional methods.


Mutability by polycyclic hydrocarbons is improved in derivatives of Escherichia coli WP2 uvrA with increased permeability.
Escherichia coli B, unlike both E. coli K12 and Salmonella typhimurium, is sensitive to the rough-specific phage C21. This sensitivity is probably due to the incomplete lipopolysaccharide core of the E. coli B cells, which confers on them a partial permeability to large molecules. Derivatives of WP2 uvrA, a tryptophan-requiring E. coli B strain, were rendered still more permeable by selecting for C21-resistant clones. The new permeable strains, when tested for mutagenesis induced by polycyclic hydrocarbons, showed a mutagenic response higher than that of the parental strains.


Comparison Between Performances of In2O3 and In2TiO5-Based EIS Biosensors Using Post Plasma CF4 Treatment Applied in Glucose and Urea Sensing.
In this study, the effect of post-deposition tetrafluoromethane (CF4) plasma treatment on the physical and electrical characteristics of an In2TiO5 based electrolyte-insulator-semiconductor (EIS) sensor was investigated. Post-deposition CF4 plasma treatment typically improved the crystalline structure and repaired dangling bonds at the grain boundaries. We used the newly fabricated device to detect several ions, such as sodium and potassium, which are essential for many biological processes. The as-deposited and CF4 plasma treated In2TiO5 sensing window with an EIS structure was also able to detect the pH of a solution, different alkali ions (Na+ and K+), glucose, and urea. The sensing membrane after a 60-sec CF4 plasma treatment displayed improved biosensing characteristics, such as higher sensitivity (59.64 mV/pH), better drift rate, and a smaller hysteresis voltage of approximately 0.424 mV/h. The In2TiO5 sensing membrane treated with CF4 plasma is a promising material for use in EIS biosensing applications.


SPECT (single photon emission computed tomography) in pediatrics.
Surgery of focal epilepsies in childhood has largely benefited from the recent advances of the noninvasive functional imaging techniques, particularly SPECT which presurgically contributes to the localization of the seizure onset zone, in order to select the patients, decide the optimal placement of intracranial electrodes, and plan the resection. Peri-ictal SPECT (ictal and postictal) proved especially useful when video-EEG is not contributory, when MRI looks normal or shows multiple abnormalities, or in cases of discrepant findings within the presurgery workup. Because of a poor temporal resolution, peri-ictal SPECT must be coupled with video-EEG. Multimodal imaging so-called SISCOM (peri-ictal - interictal SPECT subtraction image superimposed on MRI) increases the sensitivity of peri-ictal SPECT by about 70% and makes it a good predictor of seizure-free outcome after surgery. In addition, interictal SPECT occasionally provides some interesting results regarding functional cortical maturation and learning disorders in childhood.


Treatment of metastatic stromal tumors of the ovary with cisplatin, doxorubicin, and cyclophosphamide.
From September 1981 until June 1986, eight patients with metastatic ovarian stromal tumors were entered into a prospective phase II study to determine the efficacy of a chemotherapy regimen combining cisplatin, doxorubicin, and cyclophosphamide. Patients received cisplatin 40-50 mg/m2 intravenously (IV), doxorubicin 40-50 mg/m2 IV, and cyclophosphamide 400-500 mg/m2 IV, all on day 1 every 28 days. The median age was 43 years (range 24-65 years). Two patients had stage II disease, one had stage III, and five had recurrent disease (original stage: four stage I and one stage III). The median number of chemotherapy cycles was six (range four to 14). Three patients (38%) had a complete response to therapy (two confirmed by second-look laparotomy), and two patients (25%) achieved a partial response (one verified by second-look laparotomy). The overall response rate was 63%. Toxicity was minimal. Four patients are disease-free at 13+ to 48+ months, one patient is alive with disease at six+ months, and three patients are dead of tumor at four, 17, and 36 months from the start of chemotherapy. These results indicate that the combination of cisplatin, doxorubicin, and cyclophosphamide has modest activity in the treatment of metastatic ovarian stromal tumor.


Contraceptive vaginal ring--a rising star on the contraceptive horizon.
Two studies were carried out at AIIMS to judge efficacy, side-effects and acceptability of the contraceptive vaginal ring, a Silastic ring with an inner core containing 6.0 mg levonorgestrel mixed with Silastic and an outer core of Silastic only. It releases levonorgestrel at a constant rate of 20 micrograms/day and remains effective for 90 days. The first study of 50 women lasted for 12 months and the second study of 46 women lasted 24 months. Menstrual irregularity in 36% of women was the commonest reason for discontinuation. The majority of women experienced menorrhagia or irregular spotting per vaginum. Vaginal irritation or increased vaginal discharge was the second commonest reason for discontinuation and was noted in 23% of subjects. Repeated spontaneous expulsions accounted for discontinuation in 6% of subjects. No method-related failure was noted in the study. Follow-up study revealed users to be happier with the ring than with any other method and no spouse complained of feeling the ring during coitus. With its ease of administration, absence of gastrointestinal side-effects and a high success rate, the contraceptive vaginal ring is a promising contraceptive method for the last decade of the 20th century.


Indicators of infertility and fertility care: a systematic scoping review.
What is the scope of literature regarding infertility and fertility care indicators in terms of types and dimensions of these indicators? Most available infertility and fertility care indicators are outcomes indicators of effectiveness and efficiency dimensions. The use of appropriate, relevant and valid indicators of infertility and fertility care is critical for monitoring access, equity and utilization. A systematic scoping review was conducted. We searched MEDLINE, Pubmed, JSTOR, CINAHL, Web of Science and Scopus electronic databases from inception to May 2022 without imposing language or date restrictions. We searched gray literature and online libraries of relevant organizations. We hand-searched the list of relevant references. This scoping systematic review followed the framework of Arksey and O'Malley and the Joanna Briggs Institute guidelines. Records identified by the search were independently screened and data were extracted. We performed conceptual synthesis by grouping the reported indicators by typology and dimensions. Structured tabulation and graphical synthesis were used along with narrative commentary. We included 46 reports from 88 countries. The reporting of infertility and fertility care indicators was voluntary in 63 countries (72%) and compulsory in 25 countries (28%). Reporting for cycles or deliveries was based on individual cycles in 56 countries (64%) and on cumulative cycles in 32 countries (36%). Most indicators were utilized as outcome indicators with fewer being process indicators or structural indicators. For the dimension of indicators, most indicators were utilized as effectiveness and efficiency indicators with fewer utilized as indicators of safety, patient-centeredness, equity and timeliness. Most indicators fall into the domain of assisted reproductive technology and are reported by fertility clinics. Indicators of safety, patient-centeredness, equity and timeliness as well as non-clinical indicators are almost invisible. A wide range of indicators of infertility and fertility care exist in literature. Most indicators were effectiveness and efficiency indicators, while indicators of safety, patient-centeredness, equity and timeliness remain almost invisible. The scope of the current indicators indicates a predominant focus on clinical metrics, with substantial invisibility of non-clinical indicators and indicators outside the ART domain. These gaps need to be considered in further work of identifying a core set of indicators. This work received funding from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored program executed by the World Health Organization (WHO). The authors had no competing interests. Open Science Framework vsu42.


Isopropyl 3-phenyl-isoxazole-5-carboxyl-ate.
In the title compound, C13H13NO3, the isoxazole ring is approximately coplanar with the phenyl ring, the dihedral angle between their planes being 7.37 (19)°. In the crystal, centrosymmetrically related mol-ecules are linked into dimers by pairs of C-H⋯O hydrogen bonds, generating a ring of graph-set motif R 2 (2)(10).


Impact of Chronic Renal Failure on Surgical Outcomes in Patients With Infective Endocarditis.
Patients with chronic renal failure (CRF) who are undergoing hemodialysis are at increased risk for infective endocarditis (IE). However, outcomes of surgical treatment for IE in these patients have not been well studied. Between 1997 and 2017, 539 patients underwent surgical treatment for IE. Of these patients, 125 were undergoing hemodialysis for end-stage renal disease (ESRD), and 414 had no history of CRF. Primary end points compared in this study were short-term survival and long-term survival. Preoperatively, dialysis-treated patients had higher incidences of diabetes (43% vs 18%), hypertension (79% vs 49%), congestive heart failure (63% vs 48%), cardiogenic shock (13% vs 5.3), and sepsis (29% vs 18%) (all P < .05). Postoperatively, they experienced higher rates of prolonged mechanical ventilation (54% vs 22%), pneumonia (17% vs 5.6%), sepsis (6.4% vs 1.0%), cardiac arrest (7.2% vs 1.7%), gastrointestinal events (14% vs 5.1%), and operative mortality (14% vs 5.8%) (all P < .05). The 5- and 10-year survival rates were significantly worse in the dialysis-treated group at 29% and 16%, respectively, compared with 72% and 53% in the patients who did not have CRF (P < .001). ESRD was a risk factor for both short-term mortality (odds ratio, 2.0) and long-term mortality (hazard ratio, 2.7). Rates of reoperation in dialysis-treated patients were very low: 5- and 10-year incidences were 0% and 2.0%, respectively. In patients with ESRD and IE, poor postoperative outcomes emphasized the importance of prevention and raised the question whether indications for surgical treatment in the general population are appropriate for patients who are dialysis dependent. Additionally, low rates of reoperation supported the use of bioprosthetic valves in these patients.


A Statistical Atrioventricular Node Model Accounting for Pathway Switching During Atrial Fibrillation.
The atrioventricular (AV) node plays a central role in atrial fibrillation (AF), as it influences the conduction of impulses from the atria into the ventricles. In this paper, the statistical dual pathway AV node model, previously introduced by us, is modified so that it accounts for atrial impulse pathway switching even if the preceding impulse did not cause a ventricular activation. The proposed change in model structure implies that the number of model parameters subjected to maximum likelihood estimation is reduced from five to four. The model is evaluated using the data acquired in the RATe control in atrial fibrillation (RATAF) study, involving 24-h ECG recordings from 60 patients with permanent AF. When fitting the models to the RATAF database, similar results were obtained for both the present and the previous model, with a median fit of 86%. The results show that the parameter estimates characterizing refractory period prolongation exhibit considerably lower variation when using the present model, a finding that may be ascribed to fewer model parameters. The new model maintains the capability to model RR intervals, while providing more reliable parameters estimates. The model parameters are expected to convey novel clinical information, and may be useful for predicting the effect of rate control drugs.


Optic disc localization in fundus images through accumulated directional and radial blur analysis.
Optic disc localization, a key preprocessing step in the analysis of color fundus images for diagnoses of eye diseases and the localization of various anatomical structures, is particularly challenging when input retina images contain abnormalities. In such cases, the disc can be confused with other anatomical structures such as fovea, exudates, vessel tree extraction, and retinopathy-related lesions. Herein, we present a method for effective optic disc detection and localization based on color and blur analysis. In this method, the input color fundus image is converted to CIE L*a*b* color space to enhance optic disc appearance and contrast, and the accumulated directional blur and extended-maxima transform are then applied to precisely extract optic disc candidates. Subsequently, radial blur is applied to each candidate to obtain better profiles and thus distinguish the optic disc from other candidates. Finally, the full width at 80% maximum (FW80M) metric is used to select the optic disc. The performance of the proposed method is evaluated using well-studied data sets, and comparison of the obtained results with those of state-of-the-art techniques reveals the effectiveness of our method and shows that it can precisely locate the disc position not only in normal cases but also in the presence of exudates and abnormalities.


Regulation of the DNA damage response by cyclin-dependent kinases.
The eukaryotic cell cycle comprises a series of events, whose ordering and correct progression depends on the oscillating activity of cyclin-dependent kinases (Cdks), which safeguard timely duplication and segregation of the genome. Cell division is intimately connected to an evolutionarily conserved DNA damage response (DDR), which involves DNA repair pathways that reverse DNA lesions, as well as checkpoint pathways that inhibit cell cycle progression while repair occurs. There is increasing evidence that Cdks are involved in the DDR, in particular in DNA repair by homologous recombination and in activation of the checkpoint response. However, Cdks have to be carefully regulated, because even an excess of their activity can affect genome stability. In this review, we consider the physiological role of Cdks in the DDR.


Empirical calculations on cyclic dipeptides. Conformations of serine, threonine and histidine residues.
Empirical conformational energy calculations were carried out for the dipeptides cyclo-(L-Ser-L-His) and cyclo-(L-Thr-L-His). Various DKP structures have been investigated to study side chain conformations through the DKP ring deformations, and prevalent conformers of monosubstituted and disubstituted dipeptides are discussed. The most stable conformations occur when both side chains are folded over a planar DKP ring, the imidazole ring being in the epsilon-tautomeric form. Theoretical results are consistent with those obtained from n.m.r. and crystallographic studies.


Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin.
L-selectin participates in the initial attachment of leukocytes to the vascular endothelium. On lymphocytes, it mediates binding to high endothelial venules of lymph nodes. As a selectin it functions as a calcium-dependent lectin recognizing carbohydrate-bearing ligands on endothelial cells. Two lymph node ligands for L-selectin have been identified as sulphated glycoproteins of M(r) approximately 50K and approximately 90K, called Sgp50 and Sgp90 (ref. 10). The recently cloned Sgp50 (ref. 12), now designated GlyCAM-1, is a high endothelial venule-associated, mucin-like glycoprotein containing predominantly O-linked carbohydrate chains. Sialylation of GlyCAM-1 is necessary for its ligand activity and a role for fucosylation is suspected. We have used chlorate as a metabolic inhibitor of sulphation, and report here that GlyCAM-1 has an additional requirement for sulphate.


A Discourse Analysis of Quotidian Expressions of Nationalism during the COVID-19 Pandemic in Chinese Cyberspace.
By conducting discourse analysis on quotidian expressions of nationalism of Chinese netizens and analyzing their "Liking" behavior, this article tries to inductively explore during the COVID-19 pandemic what and how Chinese netizens say about nationalism. This article finds that during the pandemic, Chinese netizens show a confident and rational but confrontational and xenophobic posture in their quotidian discourses. They value reasoning and deliberation in their expressions of nationalist discourses. In the quotidian discourses, they maintain a confident tone when comparing China's performance with other countries during the pandemic, but show vigilance and even hostile sentiments toward external provocations.


Comparison of Adverse Clinical Outcomes in Children Hospitalized for Myocarditis with and Without COVID-19.
We used a nationally representative database of the US, which included 1995 myocarditis cases, among whom 620 children had COVID-19. While the risk of in-hospital mortality was not higher, illness severity and length of hospital stay were higher in patients with myocarditis and COVID-19 than those without COVID-19.


Immunologic studies of specific mucosal and systemic immune responses in Mexican school children after booster aerosol or subcutaneous immunization with measles vaccine.
The purpose of the present study was to compare serum and mucosal immune responses following either aerosol (Aer) or subcutaneous (SQ) measles immunization of Mexican school children. A cohort of 49 children from 6 to 7 years of age received either Aer ( n = 22) or SQ ( n = 27) Edmonston-Zagreb (EZ) measles vaccine. Serum and nasal secretions were collected prior to (Pre), 1 and 3 months (mos) intervals and analyzed for immunoglobulin (Ig) concentrations and measles specific Ig isotype-associated antibody by enzyme immunoassay (EIA). Serum and nasal IgG and IgA antibody responses were stimulated following immunization with live, attenuated EZ measles vaccine administered either by SQ or Aer routes but these responses were significantly greater by the Aer compared to the SQ route. These studies also suggest that the level of antibody in these secretions may serve as an important marker of immunity to measles and lend further support for aerosol immunization as an effective alternative vaccine delivery strategy for measles eradication.


The potter wasp genus Allorhynchium from Vietnam, with descriptions of three new species and a new country record (Hymenoptera, Vespidae, Eumeninae).
Species of the potter wasp genus Allorhynchium van der Vecht (Eumeninae: Odynerini) occurring in Vietnam are presented. Seven species have been recorded from Vietnam. Of them, three species are described as new to science: Allorhynchiumlatum Nguyen, Tran & MT Nguyen, sp. nov., A.moerum Nguyen & AD Nguyen, sp. nov., and A.setosum Nguyen & Engel, sp. nov., and one species, A.argentatum (Fabricius, 1804), is recorded from Vietnam for the first time. An updated key to the Oriental species of the genus is presented.


Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors.
We have compared the effect of therapy with immunosuppression alone to immunosuppression plus plasma exchange on the clinical course and rate of disappearance of antibody in 17 patients with anti-glomerular basement membrane (anti-GBM) antibody-induced renal disease. Patients receiving immunosuppression (n = 9) and those receiving plasma exchange (n = 8) were similar in terms of entry clinical characteristics, pulmonary manifestations and complications associated with therapy. Rate of disappearance of anti-GBM antibody as estimated from serial estimates of antibody binding was significantly more rapid in patients receiving plasma exchange, and mean serum creatinine in these patients at end of therapy was half that of the patients receiving immunosuppression alone. Analysis of clinical and pathologic values at study entry, however, indicated that the percent of crescents on initial renal biopsy and entry serum creatinine correlated better with outcome than did therapeutic modality. Thus, though plasma exchange may offer some advantage over immunosuppression alone in the treatment of this disease, degree of pathologic involvement appears to be the major factor affecting outcome. Patients with low cresents (less than 30%) and well preserved function did well with either treatment, while patients with severe crescentic involvement and impaired glomerular filtration rate did poorly.


Feasibility of reirradiation of recurrent sinonasal carcinoma in the periorbital region using hypofractionated image-guided intensity-modulated radiation therapy.
Recurrent periorbital tumors pose management challenges because they are often unresectable and chemorefractory. Proximity to critical structures renders reirradiation difficult. With image-guided intensity-modulated radiation therapy (IG-IMRT), real-time corrections to patient setup are possible, enabling significant shrinkage of planning target volume margins and safe dose escalation with hypofractionation. Here, we present our experience with hypofractionated IG-IMRT in a patient with multiply recurrent sinonasal carcinomas in the periorbital region. The patient is a 67-year-old woman with sinonasal carcinoma, treated with surgery and 2 prior courses of high-dose radiotherapy. She developed a second tumor recurrence in the right lateral orbit, which was reirradiated using hypofractionated IG-IMRT (24 Gy in 3 fractions). Near-complete resolution of her ocular symptoms was observed at 4 months. Progress scans demonstrated a decrease in size of the orbital lesion. Preliminary results of reirradiation using hypofractionated IG-IMRT suggest that it is safe and effective.


Sperm quality assessed by flow cytometry and accessory sex gland function in spinal cord injured men after repeated vibration-induced ejaculation.
Semen was obtained by vibration-induced ejaculation from 5 spinal injured men once a week for 5 consecutive weeks under standardised conditions. The site of the spinal lesions varied from C5 to Th10. Although in all subjects except one, the total sperm count in the first ejaculate was within normal limits, conventional criteria indicated a high degree of asthenoteratozoospermia in all cases. In subsequent ejaculates there was no major general improvement in motility, vitality or morphology. However, 2 individuals exhibited a marked increase in the proportion of motile sperm in the ejaculate over the next 3 weeks. Flow cytometry of the same sperm samples indicated a high degree of abnormal chromatin condensation and reduced binding of a fluorescent acrosomal marker in the first ejaculates. No improvement in these parameters could be detected with time. Assessment of accessory sex gland function using specific secretory markers indicated that compared to the normal population, the vesicular contribution was markedly reduced in 3 subjects and prostatic contribution in the 2 remaining subjects in the first and subsequent ejaculations. Ejaculate volumes were consistently low in all subjects during the observation period. In contrast, total epididymal secretion was comparable to normal ejaculates. Prostatic contributions to the ejaculate increased significantly over the first 4 weeks. In conclusion, regular vibration-induced ejaculation at weekly intervals could not improve sperm quality in paraplegic men to an acceptable degree for assisted fertilisation to be recommended. Although certain aspects of sperm quality, as judged by conventional criteria, were improved in some cases, flow cytometry revealed persistent chromatin and acrosomal abnormalities.


Antioxidant activity of Cinnamomum cassia.
The antioxidant activities of hot water extracts (HWECC) and ethanol extracts (EECC) from the dry bark of Cinnamomum cassia Presl were evaluated in this study. Results showed that at 1.0 mg/mL, the ethanol extracts of C. cassia (96.30%) exhibited a greater inhibition than the alpha-tocopherol (93.74%) on FeCl(2)-ascorbic acid induced lipid peroxidation of rat liver homogenate in vitro. From 0.05 to 1.0 mg/mL, the EECC demonstrated the highest superoxide anions scavenging activity and the strongest anti-superoxide formation activity (p < 0.05). The same extract also showed an excellent antioxidant activity in enzymatic and nonenzymatic liver tissue oxidative systems. EECC revealed the strongest antioxidant activity followed by alpha-tocopherol and HWECC. Compared to alpha-tocopherol, the IC(50) values of EECC were found to be lower in thiobarbituric acid test (IC(50) = 0.24 mg/mL vs 0.37 mg/mL), in cytochrome c test (IC(50) = 0.16 mg/mL vs 0.27 mg/mL) and in xanthine oxidase inhibition test (IC(50) = 0.09 mg/mL vs 0.19 mg/mL). The present study concludes that EECC could be used as a good source of antioxidant in the dietary supplement.


A red-green photochromic bacterial protein as a new contrast agent for improved photoacoustic imaging.
The GAF3 domain of the cyanobacteriochrome Slr1393 from Synechocystis sp. PCC6803, binding phycocyanobilin as a chromophore, shows photochromicity between two stable, green- and red-absorbing states, characterized by relatively high photoconversion yields. Using nanosecond-pulsed excitation by red or green light, respectively, and suitable cw photoconversion beams, we demonstrate that the light-modulatable photoacoustic waveforms arising from GAF3 can be easily distinguished from background signals originating from non-modulatable competitive absorbers and scattering media. It is demonstrated that this effect can be exploited to identify the position of the photochromic molecule by using as a phantom a cylindrical capillary tube filled with either a GAF3 solution or with an E.coli suspension overexpressing GAF3. These properties identify the high potential of GAF3 to be included in the palette of genetically encoded photochromic probes for photoacoustic imaging.


MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats.
MKC-231 is reported to increase high-affinity choline uptake (HACU) in vitro and improve learning impairment on a single oral administration in AF64A-treated rats. In this study, we investigated the effects of repeated administration of MKC-231 (1 and 3 mg/kg, p.o., 8 days) on learning impairment in the water-maze task in AF64A-treated rats 1, 24, 48, and 72 h after the last dose. Significant cognitive improvement was observed for 24 h, however, concentration measurement studies indicated MKC-231 was not detected in the brain by this time. We also studied the effects of 8-days repeated administration of MKC-231 on HACU 1, 24, 48, and 72 h after the last dose and observed an increase of HACU similar in time course with cognitive improvement. From these results, we discussed the possibility that MKC-231 could induce long-lasting procognitive effects by changing the choline transporter regulation system.


Hollow capsules prepared from all block copolymer micelle multilayers.
We introduce a novel and versatile approach for preparing hollow multilayer capsules containing functional hydrophobic components. Protonated polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) and anionic polystyrene-block-poly(acrylic acid) (PS-b-PAA) block copolymer micelles (BCM) were used as building blocks for the layer-by-layer assembly of BCM multilayer films onto polystyrene (PS) colloids. After removing the PS colloids, the stabilities of the formed BCM hollow capsules were found to be strongly dependent on the charge density of the hydrophilic corona segments (i.e., P4VP and PAA block segments) as well as the relative molecular weight ratio of hydrophobic core (i.e., PS segments) blocks and hydrophilic corona shells. Furthermore, in the case of incorporating hydrophobic fluorescent dyes into the PS core blocks of micelles, the hairy/hairy BCM multilayers showed well-defined fluorescent images after colloidal template removal process. These phenomena are mainly caused by the relatively high degree of electrostatic interdigitation between the protonated and anionic corona block shells.


A rat uterine horn model of genital tract wound healing.
A rat uterine horn model of genital tract wound healing is described. Healing was reflected by acquisition of strength and elasticity, measured by burst strength (BS) and extensibility (EX), respectively. A tensiometer (Instron Corp., Canton, MA) was used to assess these characteristics in castrated and estrogen-supplemented or nonsupplemented animals. While the horn weights (HW), BS, and EX of contralateral horns were not significantly different, the intra-animal variation of HW was 7.2%, BS was 17.7% and EX was 38.2%. In a second experiment, one uterine horn was divided and anastomosed, and the animal given estrogen supplementation or a placebo pellet. Estrogen administration was found to increase BS and EX of anastomosed horns prior to 14 days, but had no beneficial effect at 21 or 42 days. The data suggest that estrogen may be required for optimal early healing of genital tract wounds.


Elevation of serum CXC chemokine ligand-12 levels predicts poor outcome after aneurysmal subarachnoid hemorrhage.
CXC chemokine ligand-12 (CXCL12) is involved in the innate immune system. Elevation of its level in the peripheral blood is associated with severity and outcome of ischemic stroke. This study aimed to investigate its relation to severity and prognosis following aneurysmal subarachnoid hemorrhage (aSAH). Serum CXCL12 levels were determined in a total of 182 controls and 182 aSAH patients. Hemorrhagic severity was assessed using the World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale. Unfavorable outcome was defined as Glasgow outcome scale score of 1-3. Prognostic predictors of 6-month mortality and unfavorable outcome were identified using multivariate analysis. The serum CXCL12 levels were significantly higher in patients as compared to controls (14.5±6.7ng/mL vs. 1.7±0.6ng/mL, P<0.001) and were independently associated with WFNS scores (t=5.927, P<0.001) and modified Fisher scores (t=5.506, P<0.001). Serum CXCL12 levels predicted 6-month mortality and 6-month unfavorable outcome with the area under curves of 0.815 [95% confidence (CI), 0.751-0.868] and 0.809 (95% CI, 0.745-0.864) respectively and were related independently to 6-month mortality (odds ratio, 4.428; 95% CI, 1.977-12.031; P=0.004) and 6-month unfavorable outcome (odds ratio, 3.821; 95% CI, 1.097-9.251; P=0.001). Moreover, the predictive values of CXCL12 levels were in the range of WFNS scores and modified Fisher scores. Elevation of serum CXCL12 levels is associated highly with hemorrhagic severity and poor outcome after aSAH, suggesting CXCL12 might have the potential to be a prognostic predictive biomarker of aSAH.


Impact of information systems on acute care hospitals: results from a survey in the United States.
These results are from a survey of acute care hospitals in the United States. A random sample of 813 hospitals was selected with 115 responding and 33 incorrect addresses resulting in a 15% response rate. The purpose of the study was to measure the impact and future potential of information systems integration in the financial, medical, and administrative systems of the hospitals. Impact of Information Systems is measured in many ways. Questions about employee moral, reductions in employees, goals being met and overall satisfaction with the systems are asked and results analyzed. This information will provide a benchmark for hospitals to determine their information systems position and technology transfer planning. These analyses will lead to setting goals.


Neonatal transient respiratory depression after maternal urapidil infusion for hypertension.
Urapidil is a potent antihypertensive drug that has been in clinical use for more than 20 years. It has been proven to be an effective and well-tolerated antihypertensive drug during pregnancy, but clinical experiences with urapidil have been described in only a limited number of studies. There have also been only limited observations on the (side-)effects of urapidil on the neonate. We describe here a case of postnatal transient respiratory depression following maternal administration of urapidil. We suggest that the fetal and neonatal effects of more recently implemented antihypertensive drugs, such as urapidil, should be included in a prospective evaluation of antihypertensive treatment of women during pregnancy. Infants of mothers who received urapidil should be carefully watched in the immediate postnatal phase as urapidil may still exert some significant effects on the neonate.


Isotachophoresis of proteins.
The analytical separation of proteins by isotachophoresis (ITP) was achieved in a short electrophoretic path and with a resolution comparable to that of isoelectric focusing by the appropriate selection of (1) a mixture of ampholytes as spacers to generate linear gradients of electrophoretic mobility and (2) the counter ions chosen to buffer the complete pH gradient generated. This ITP technique is exemplified by the analysis of plasma proteins in agarose gels. Upto 46 samples in the same gel plate were analysed. The resolution was such that at least 30 clear and discrete bands per sample could be observed after staining with Coomassie Brilliant Blue. The resolving power of ITP could be further increased for the study of a particular protein or zone by the selection of suitable spacers and counter ions.


No genetic association between alpha-2 macroglobulin I1000V polymorphism and Japanese sporadic Alzheimer's disease.
Alpha-2 macroglobulin (A2M) is a serum pan-protease inhibitor that is related with the pathogenesis of Alzheimer's disease (AD) through its ability to mediate amyloid beta degradation. Recently, it has been reported that the I1000V polymorphism in A2M gene might increase the risk of AD. In the present study, we investigated this mutation in 95 healthy controls and in 111 sporadic AD cases by polymerase chain reaction-restriction fragment length polymorphism method in order to study this hypothesis in the Japanese AD population. Allelic frequencies with the I1000V polymorphism in the gene were 7.4 and 6.8% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD, and the A2M I1000V mutation does not seem to be a risk factor per se for sporadic AD.


A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.
Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 × 10⁻⁹ to P(trend) = 3.9 × 10⁻⁷), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P(trend) = 1 × 10⁻⁷) to P(trend) = 8 × 10⁻⁵; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 × 10⁻⁷


Middle ear cholesteatoma prevalence in over 3,600 children with Turner Syndrome.
To investigate the prevalence of middle ear cholesteatoma in children with Turner syndrome (TS) as compared to the general population using a large database. The TriNetx Analytics Network, a federated health research network that aggregates the de-identified electronic health record data of over 78 million patients across the United States, was queried for patients 18 years old or younger with TS. Patients in this group with any occurrence of a diagnosed middle ear cholesteatoma were recorded and reported. Out of 3,682 children 18 years old or younger with diagnosed TS, 1.47% (95% CI: 1.10%-1.91%) had a history of middle ear cholesteatoma. Out of 12,836,624 children 18 years or younger without TS, 0.09% (95% CI: 0.09%-0.09%) had a history of diagnosed middle ear cholesteatoma. The relative risk for middle ear cholesteatoma in children with TS was 16.74 (95% CI: 12.84-21.83). The relative risk for diagnosed cleft palate among children with TS was 8.56 (95% CI: 6.67-10.98) which, because of the Eustachian tube dysfunction in this population, may contribute to the cholesteatoma risk. The rate of diagnosed middle ear cholesteatoma was found to be 16 times higher in patients with Turner syndrome versus children without Turner syndrome. Of studies examining middle ear cholesteatoma in children with TS, the present study has the largest sample size thus providing reliable evidence for prevalence in this population. Clinical monitoring for cholesteatoma should be especially rigorous and frequent in this population.


Urosepsis associated with videourodynamic studies.
Videourodynamic studies (VUS) of the lower urinary tract are useful in the evaluation of complicated voiding dysfunctions. These studies involve placement of urethral and rectal catheters, measurement of pressures during bladder filling and voiding, and simultaneous fluoroscopic cystourethrography. A cluster of five cases of urosepsis occurred in patients examined with VUS between November 1981 and February 1982. Pseudomonas aeruginosa was cultured from the blood and/or urine of three of these patients. P. aeruginosa was also recovered from cultures of fluid within the stopcock-tubing-syringe apparatus used to connect the urethral catheter to the pressure transducer. The temporal relationship of urosepsis to the VUS procedure and the identification of an environmental reservoir of P. aeruginosa suggest that these episodes were related to VUS.


Sulfamethoxazole induces brain capillaries toxicity in zebrafish by up-regulation of VEGF and chemokine signalling.
Sulfamethoxazole (SMX) is a widespread broad-spectrum bacteriostatic antibiotic. Its residual is frequently detected in the water and may therefore bioaccumulate in the brain of aquatic organisms via blood circulation. Brain capillaries toxicity is very important for brain development. However, little information is available in the literature to show the toxicity of SMX to brain development. To study the SMX's brain toxic effects and the related mechanisms, we exposed zebrafish embryos to SMX at different concentrations (0 ppm, 1 ppm, 25 ppm, 100 ppm and 250 ppm) and found that high concentration (250 ppm) of SMX would not only caused an abnormal in malformation rate, hatching rate, body length and survival rate of zebrafish embryos, but also lead to brain oedema. In addition, SMX also induced cerebral ischaemia, aggravates oxidative stress, and changes genes related to oxidative stress (sod1, cat, gpx4, and nrf2). Furthermore, ischaemia caused by SMX could promote ectopic angiogenesis in brain via activating the angiogenesis-related genes (vegfab, cxcr4a, cxcl12b) from 24 h to 53 h. Inhibition of VEGF signalling by SU5416, or inhibition of chemokine downstream PI3K signalling by LY294002, could rescue the brain capillaries toxicity and brain oedema induced by SMX. Our results provide new evidence for the brain toxicity of SMX and its residual danger in the environment and aquatic organisms.


Hepatocellular carcinoma in children.
Liver tumors are relatively rare in childhood, but may be associated with a range of diagnostic, genetic, therapeutic, and surgical challenges sufficient to tax even the most experienced clinician. This article outlines the epidemiology, etiology, pathologic condition, initial workup, and management of hepatocellular carcinoma in children and adolescents.


From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
Myelodysplastic syndrome (MDS), a clonal disorder originating from hematopoietic stem cell, is characterized by a progressive character often leading to transformation to acute myeloid leukemia. We used single nucleotide polymorphism arrays (SNP-A) to identify previously cryptic chromosomal abnormalities such as copy number alterations and uniparental disomies (UPD) in cytogenetically normal MDS. In the aberrant regions, we attempted to localize candidate genes with potential relevance to the disease. Using SNP-A, we analyzed peripheral blood granulocytes from 37 MDS patients. The analysis identified 13 cryptic chromosomal defects in 10 patients (27%). Four UPD (affecting chromosomes 3q, 7q, 17q, and 20p), 5 deletions and 4 duplications were detected. Gene expression data measured on CD34+ cells were available for 4 patients with and 6 patients without SNP-A lesions. We performed an integrative analysis of genotyping and gene expression microarrays and found several genes with an altered expression located in the aberrant regions. The expression microarrays suggested BMP2 and TRIB3 located in 20p UPD as potential candidate genes contributing to MDS. We showed that the genome-wide integrative approach is beneficial to the comprehension of molecular backgrounds of diseases with incompletely understood etiopathology.


[Identification of marsdeniae tenacissimae caulis and its adulterants by RAPD].
To identify Marsdeniae Tenacissimae Caulis and its adulterants by RAPD (random amplified polymorphic DNA) and analyze the gene homology of Marsdeniae Tenacissimae Caulis from various habitats. General DNA was isolated from Marsdeniae tenacissimae Caulis which were from seven various habitats and its six adulterants by CTAB, the twenty RAPD was used to identify them. Random primer 285 (GGG AAC CCT T) could amplify the gene of Marsdeniae tenacissimae Caulis from various habitats stablely, Marsdeniae tenacissimae Caulis and its adulterants could be identified by primer E01 (CCC AAG GTC C) effectively. The method of RAPD can be used to identify Marsdeniae Tenacissimae Caulis and its adulterants, the gene of Marsdeniae tenacissimae Caulis from various habitats have homology.


Exploring mediation pathways on the relationship between acculturation and binge eating among Latino adolescents.
The objective of this study was to explore the mediating effects of emotional eating, restrained eating, and external eating on the relationship between acculturation and binge eating among Latino adolescents. Adolescents who self-identified as Latino (N = 285) at public high schools in Southern California were recruited and completed a self-report survey. Acculturation was assessed using the 8-item Acculturation, Habits, Interests for Multicultural Adolescents (AHIMSA) scale for adolescents, mediators were assessed using Dutch Eating Behavior Questionnaire (DEBQ), and binge eating was assessed using a 13-item Eating Disorder Diagnostic Scale. A bootstrapped multiple mediation model was used to test mediation pathways. Findings suggest that individually each eating style-emotional, restrained and external eating pathway did not reach significance singly, but that jointly, their combined effect was significant with a total indirect effect (B = 0.15, CI 0.01-0.30) indicating an additive effect of the three eating styles. Future research should examine additional mediators of the relationship between acculturation and binge eating.


Energy flow and the vertical structure of real ecosystems.
Three possible explanations for the well-known limitation of food chain lengths to two or three links for the most part are subjected to an empirical test, using the fact that ectotherms, especially invertebrates, tend to have higher production efficiencies than endotherms. The data are consistent with the hypothesis that food chain lengths are limited by the availability of energy.


Structural insights into the role of DNA-PK as a master regulator in NHEJ.
DNA-dependent protein kinase catalytic subunit DNA-PKcs/PRKDC is the largest serine/threonine protein kinase of the phosphatidyl inositol 3-kinase-like protein kinase (PIKK) family and is the most highly expressed PIKK in human cells. With its DNA-binding partner Ku70/80, DNA-PKcs is required for regulated and efficient repair of ionizing radiation-induced DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway. Loss of DNA-PKcs or other NHEJ factors leads to radiation sensitivity and unrepaired DNA double-strand breaks (DSBs), as well as defects in V(D)J recombination and immune defects. In this review, we highlight the contributions of the late Dr. Carl W. Anderson to the discovery and early characterization of DNA-PK. We furthermore build upon his foundational work to provide recent insights into the structure of NHEJ synaptic complexes, an evolutionarily conserved and functionally important YRPD motif, and the role of DNA-PKcs and its phosphorylation in NHEJ. The combined results identify DNA-PKcs as a master regulator that is activated by its detection of two double-strand DNA ends for a cascade of phosphorylation events that provide specificity and efficiency in assembling the synaptic complex for NHEJ.


Perineal abscess eight years after total proctocolectomy for ulcerative colitis.
Total proctocolectomy following surgery for ulcerative colitis and carcinoma may be associated with difficulty in healing of the perineal wound. The presentation of delayed abscesses may be insidious in nature and present a diagnostic dilemma. We present a patient with delayed abscess eight years following total proctocolectomy for ulcerative colitis. Early use of computerized tomography is helpful in evaluating the late occurrence of pain in these patients.


Unusual solution properties of proline and its interaction with proteins.
Proline in aqueous solution shows several properties which are unusual for low molecular weight substances. Investigations of solubility, density and viscosity revealed behaviour which is characteristic for hydrophilic colloids. 1H-NMR studies indicated a strong hydrogen bonding of water in proline solutions, especially at high concentrations of the solute. From these results it was concluded that proline forms aggregates by stepwise stacking and hydrophobic interaction of the pyrrolidine ring. Thus, the proposed multimer contans a hydrophobic backbone and hydrophilic groups on the surface, exposed to water. Proline solutions are able to increase the solubility of sparingly soluble proteins. The enhancement effect depends on the nature of the protein and on the proline concentration. It is postulated that by a hydrophobic interaction of proline with hydrophobic surface residues of proteins their hydrophilic area is increased. The presence of proline in solutions of the well soluble protein bovine albumin reduces the precipitation of this protein by ethanol and (NH4)2SO4, presumably by an increased water-binding capacity of the proline-protein solution.


Bone marrow oedema syndrome of the foot and ankle in a paediatric population: a retrospective case series with serial MRI evaluation.
By means of a case series we wanted to describe and correlate the clinical and imaging features of bone marrow oedema syndrome (BMOS) of the foot and ankle in children. A retrospective data study was performed on patients born on or after 01 January 2001 who underwent multiple MRI scans of the foot and ankle for pain symptoms. Six patients who presented with increased signal intensity on T2-weighted MR imaging without any underlying causes or concomitant pathology were included. All patients, three boys and three girls with a mean age of 11 years (8 to 14), displayed patchy areas of increased signal intensity on T2-weighted and turbo inversion recovery magnitude (TIRM) images. On average, six tarsal bones were involved (4 to 8). In all patients, treatment consisted of rest and/or protected weight-bearing. The mean time for symptoms to improve during treatment was 6 months (1 to 16). The mean duration of treatment was nine months (3 to 16). In all patients clinical and imaging symptoms were strongly correlated and regressed in time. BMOS as a pathological entity should be considered in paediatric patients with foot and ankle pain without a clear underlying cause, and characteristic T2-weighted and TIRM signal intensity increase on MRI images. As BMOS is transient and self-limiting, conservative treatment is advised while the oedema regresses. An early diagnosis of this pathology could prevent unnecessary diagnostic investigations and invasive treatments. IV.


The respiratory tract microbiome, the pathogen load, and clinical interventions define severity of bacterial pneumonia.
Bacterial pneumonia is a considerable problem worldwide. Here, we follow the inter-kingdom respiratory tract microbiome (RTM) of a unique cohort of 38 hospitalized patients (n = 97 samples) with pneumonia caused by Legionella pneumophila. The RTM composition is characterized by diversity drops early in hospitalization and ecological species replacement. RTMs with the highest bacterial and fungal loads show low diversity and pathogen enrichment, suggesting high biomass as a biomarker for secondary and/or co-infections. The RTM structure is defined by a "commensal" cluster associated with a healthy RTM and a "pathogen" enriched one, suggesting that the cluster equilibrium drives the microbiome to recovery or dysbiosis. Legionella biomass correlates with disease severity and co-morbidities, while clinical interventions influence the RTM dynamics. Fungi, archaea, and protozoa seem to contribute to progress of pneumonia. Thus, the interplay of the RTM equilibrium, the pathogen load dynamics, and clinical interventions play a critical role in patient recovery.


BofC negatively regulates SpoIVB-mediated signalling in the Bacillus subtilis sigmaK-checkpoint.
The BofC protein acts negatively on intercompartmental signalling of pro-sigma(K) processing in the sigma(K)-checkpoint of Bacillus subtilis. Signalling is brought about by the SpoIVB protein, which is synthesized in the forespore and initiates proteolytic processing of pro-sigmaK to its mature and active form in the opposed mother cell chamber of the developing cell. We have shown here that BofC, like SpoIVB, is secreted across the inner forespore membrane and, from the analysis of a bofC deletion and insertion mutant, is likely to interact with SpoIVB. In the absence of BofC, the amount of SpoIVB found in sporulating cells is substantially reduced, although SpoIVB is still able to activate proteolysis of pro-sigma(K). Conversely, in the absence of SpoIVB, the levels of BofC accumulate suggesting that the fate of each molecule is dependent upon their mutual interaction. Our results suggest that BofC could maintain SpoIVB in a stable but inactive form. Supporting this, we have shown that overproduction of BofC inhibits SpoIVB autoproteolysis and leads to a delay in proteolytic cleavage of pro-sigma(K). Based on our work here, we have proposed a model for BofC's functional role in intercompartmental signalling.


Meningeal cysticercosis diagnosed in Western Australia.
Two cases of the relatively unusual meningeal form of intracranial cysticercosis are described in adult Italian immigrants to Western Australia. Each presented solely with raised intracranial pressure caused by communicating hydrocephalus in association with chronic meningitis, characterized by a very low cerebrospinal fluid glucose level. The diagnosis was confirmed histologically on tissue obtained fortuitously at lumbar puncture. These cases draw attention to the epidemiological implications of cysticercosis in the Australian scene. As well, they demonstrate that repeated cerebrospinal fluid analysis may result in diagnostic confirmation of intracerebral cysticercosis of the racemose type.


Hypomyelinating spastic dyskinesia and ichthyosis caused by a homozygous splice site mutation leading to exon skipping in ELOVL1.
Next generation sequencing technologies allow detection of very rare pathogenic gene variants and uncover cerebral palsy. Herein, we describe two siblings with cerebral palsy due to ELOVL1 splice site mutation in autosomal recessive manner. ELOVL1 catalyzes fatty acid elongation to produce very long-chain fatty acids (VLCFAs; ≥C21), most of which are components of sphingolipids such as ceramides and sphingomyelins. Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies (MIM: 618527) stem from ELOVL1 gene deficiency in human. We have studied a consanguineous family with whole exome sequencing (WES) and performed in depth analysis of cryptic splicing on the molecular level using RNA. Comprehensive analysis of ceramides in the skin stratum corneum of patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS). ELOVL1 protein structure was computationally modelled. The novel c.376-2A > G (ENST00000372458.8) homozygous variant in the affected siblings causes exon skipping. Comprehensive analysis of ceramides in the skin stratum corneum of patients using LC-MS/MS demonstrated significant shortening of fatty acid moieties and severe reduction in the levels of acylceramides. It has recently been shown that disease associated variants of ELOVL1 segregate in an autosomal dominant manner. However, our study for the first time demonstrates an alternative autosomal recessive inheritance model for ELOVL1. In conclusion, we suggest that in ultra-rare diseases, being able to identify the inheritance patterns of the disease-associated gene or genes can be an important guide to identifying the molecular mechanism of genetic cerebral palsy.


Drug-Induced Loss of Preexcitation in Pediatric Patients with WPW Pattern During Electrophysiologic Study.
Ablation of accessory pathways (AP) is one of the most often performed procedures in pediatric electrophysiology. In pediatric patients these procedures are mostly performed in anaesthesia or sedation. In some of these patients who are referred for electrophysiologic (EP) study, we could observe disappearance of the preexcitation, i.e. antegrade conduction of an AP during introduction of sedation. As a suppression of AP conduction capacities has been reported as negative side effect of propofol and other anaesthetics, the aim of this study was to evaluate risk factors for drug-induced suppression of AP conduction properties. Consecutive, pediatric patients with Wolff-Parkinson-White (WPW) pattern referred for EP study in the period of 2016-2017 were reviewed in retrospect. Patients with complex congenital heart disease were excluded. An entire chart review including ECG, bicycle stress testing, and periprocedural data was performed. In 4 of 37 patients included into the study, loss of preexcitation could be observed during sedation. Data analysis showed weaker conduction capacities of the AP as a risk factor (p = 0.009). Interestingly, absolute (p = 0.11) or adjusted to body weight (p = 0.92) drug doses were not a relevant risk factor. Patients with WPW and weaker conduction capacities of the AP, as implied by an early disappearance of preexcitation during exercise stress testing, seem to be more prone to drug-induced suppression of an AP.