Risk of Streptococcus pneumoniae-associated haemolytic uraemic syndrome in industrialised nations: a systematic review of the literature.

BACKGROUND AND AIM: Haemolytic uraemic syndrome (HUS) is a triad of haemolytic anaemia, thrombocytopaenia, and acute kidney injury. It is a leading cause of acute kidney injury in children and has a high rate of long-term sequelae. Streptococcus pneumoniae-associated HUS (SpHUS) is a rare complication from pneumococcal disease. This article aims to systematically review SpHUS following the global introduction of pneumococcal conjugate vaccines (PCVs). MATERIAL AND METHODS: A comprehensive literature search was conducted in MEDLINE, EMBASE, and the Cochrane library from 1st January 2000 to 13th April 2022. RESULTS: Thirteen studies were included in this review, involving a total of 7,177 children with HUS, of which 336 cases were associated with Streptococcus pneumoniae. SpHUS accounted for 4.8% of all HUS cases, in which most patients were younger than 24 months old. Nine studies (80.4%, 281) were during the country's PCV era, whereas 4 studies (19.6%, 66) were before the introduction of PCV into the national vaccination programme. Pneumonia was the commonest clinical presentation (77.3%; 75/97), followed by septicaemia (33.0%; 32/97), and meningitis (29.9%; 29/97). Most cases presenting with pneumonia were complicated by empyema or pleural effusion (54.4%, n=49/90). Only 5 studies reported the isolated serotypes, with the most prevalent serotype being 19A (44.4%, n=20/45), followed by serotype 3 (17.8%, n = 8/45) and 7F (6.7%, n = 3/45). Of those reporting fatality, there were 12 deaths with a fatality rate of 9.8% (n = 12/122). CONCLUSION: SpHUS is rare, but commonly presents in children younger than 2 years old. There remains a high risk of long-term complications and relatively high mortality rate even in the era of conjugate vaccines.

Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer.

BACKGROUND: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival. METHODS: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used. RESULTS: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients. CONCLUSION: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer.

BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.

Investigation of availability and accessibility of community automated external defibrillators in a territory in Hong Kong.

OBJECTIVE: To evaluate the availability and accessibility of community automated external defibrillators in a territory in Hong Kong. DESIGN: Cross-sectional study. SETTING: Two public hospitals in New Territories West Cluster in Hong Kong. PARTICIPANTS: Information about the locations of community automated external defibrillators was obtained from automated external defibrillator suppliers and through community search. Data on locations of out-of-hospital cardiac arrests from August 2010 to September 2013 were obtained from the local cardiac arrest registry of the emergency departments of two hospitals. Sites of both automated external defibrillators and out-of-hospital cardiac arrests were geographically coded and mapped. The number of out-of-hospital cardiac arrests within 100 m of automated external defibrillators per year and the proportion of out-of-hospital cardiac arrests with accessible automated external defibrillators (100 m) were calculated. The number of community automated external defibrillators per 10,000 population and public access defibrillation rate were also calculated and compared with those in other countries. RESULTS: There were a total of 207 community automated external defibrillators in the territory. The number of automated external defibrillators per 10,000 population was 1.942. All facilities with automated external defibrillators in this territory had more than 0.2 out-of-hospital cardiac arrests per automated external defibrillator per year within 100 m. Among all out-of-hospital cardiac arrests, 25.2% could have an automated external defibrillator reachable within 100 m. The public access defibrillation rate was 0.168%. CONCLUSIONS: The number and accessibility of community automated external defibrillators in this territory are comparable to those in other developed countries. The placement site of community automated external defibrillators is cost-effective. However, the public access defibrillation rate is low.

Sequence analysis and gene expression of putative oil palm chitinase and chitinase-like proteins in response to colonization of Ganoderma boninense and Trichoderma harzianum.

Chitinases are glycosyl hydrolases that cleave the ß-1,4-glycosidic linkages between N-acetylglucosamine residues in chitin which is a major component of fungal cell wall. Plant chitinases hydrolyze fungal chitin to chitin oligosaccharides that serve as elicitors of plant defense system against fungal pathogens. However, plants synthesize many chitinase isozymes and some of them are not pathogenesis-related. In this study, three full-length cDNA sequences encoding a putative chitinase (EgChit3-1) and two chitinase-like proteins (EgChit1-1 and EgChit5-1) have been cloned from oil palm (Elaeis guineensis) by polymerase chain reaction (PCR). The abundance of these transcripts in the roots and leaves of oil palm seedlings treated with Ganoderma boninense (a fungal pathogen) or Trichoderma harzianum (an avirulent symbiont), and a combination of both fungi at 3, 6 and 12 weeks post infection were profiled by real time quantitative reverse-transcription (qRT)-PCR. Our findings showed that the gene expression of EgChit3-1 increased significantly in the roots of oil palm seedlings treated with either G. boninense or T. harzianum and a combination of both; whereas the gene expression of EgChit1-1 in the treated roots of oil palm seedlings was not significantly higher compared to those of the untreated oil palm roots. The gene expression of EgChit5-1 was only higher in the roots of oil palm seedlings treated with T. harzianum compared to those of the untreated oil palm roots. In addition, the gene expression of EgChit1-1 and EgChit3-1 showed a significantly higher gene expression in the leaf samples of oil palm seedlings treated with either G. boninense or T. harzianum.

Rapid movement of axonal neurofilaments interrupted by prolonged pauses.

Axonal cytoskeletal and cytosolic proteins are synthesized in the neuronal cell body and transported along axons by slow axonal transport, but attempts to observe this movement directly in living cells have yielded conflicting results. Here we report the direct observation of the axonal transport of neurofilament protein tagged with green fluorescent protein in cultured nerve cells. Live-cell imaging of naturally occurring gaps in the axonal neurofilament array reveals rapid, intermittent and highly asynchronous movement of fluorescent neurofilaments. The movement is bidirectional, but predominantly anterograde. Our data indicate that the slow rate of slow axonal transport may be the result of rapid movements interrupted by prolonged pauses.

High frequency plant regeneration from mature seed of elite, recalcitrant Malaysian indica rice ( Oryza sativa L.) CV. MR 219.

An efficient in vitro plant regeneration system was established for elite, recalcitrant Malaysian indica rice, Oryza sativa L. CV. MR 219 using mature seeds as explant on Murashige and Skoog and Chu N6 media containing 2,4-dichlorophenoxy acetic acid and kinetin either alone or in different combinations. L-proline, casein hydrolysate and L-glutamine were added to callus induction media for enhancement of embryogenic callus induction. The highest frequency of friable callus induction (84%) was observed in N6 medium containing 2.5 mg l(-1) 2,4-dichlorophenoxy acetic acid, 0.2 mg l(-1) kinetin, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate, 20 mg l(-1) L-glutamine and 30 g l(-1) sucrose under culture in continuous lighting conditions. The maximum regeneration frequency (71%) was observed, when 30-day-old N6 friable calli were cultured on MS medium supplemented with 3 mg l(-1) 6-benzyl aminopurine, 1 mg l(-1) naphthalene acetic acid, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate and 3% maltose. Developed shoots were rooted in half strength MS medium supplemented with 2% sucrose and were successfully transplanted to soil with 95% survival. This protocol may be used for other recalcitrant indica rice genotypes and to transfer desirable genes in to Malaysian indica rice cultivar MR219 for crop improvement.

Live cell tracking based on cellular state recognition from microscopic images.

The analysis of cell motion is an essential process in fundamental medical studies because most active cellular functions involve motion. In this paper, a computer-assisted motion analysis system is proposed for cell tracking. In the proposed tracking process, unlike in conventional tracking methods, cellular states referring to the cellular life cycle are defined and appropriate strategies are adopted for cells at different states. The use of cellular state recognition allows detection of possible cell division and hence can improve the robustness of cell tracking. Experimental results show that cells can be successfully segmented and tracked over a long period of time, and the proposed system is found to be as accurate as manual tracking. Various quantitative analyses and visualizations are used to represent cell motion, which demonstrates the usefulness of the proposed system in the study of cell dynamics.

Synthesis of platinum(II) and palladium(II) complexes with 9,9-dihexyl-4,5-diazafluorene and their in vivo antitumour activity against Hep3B xenografted mice.

Two complexes dichloro(9,9-dihexyl-4,5-diazafluorene)platinum(II) (Pt-DHF) and dichloro(9,9-dihexyl-4,5-diazafluorene)palladium(II) (Pd-DHF) were synthesized and their in vivo antitumour activity was investigated using an athymic nude mice model xenografted with human Hep3B carcinoma cells. Pt-DHF- and Pd-DHF-treated groups showed significant tumour growth inhibition (with about 9-fold and 3-fold tumour growth retardation) when compared with the vehicle control group. The liver toxicology effects on the animals of the two compounds were investigated. Pt-DHF and Pd-DHF-treated groups had a lower alanine transaminase and aspartate transaminase values than those of the vehicle treated group as the animals from the vehicle control group had very heavy hepatoma burden. We assume that both complexes could be further investigated as effective antitumour agents and it is worthwhile to study their underlying working mechanism.

Purification and characterization of a lethal protein with phospholipase A1 activity from the hornet (Vespa basalis) venom.

The hornet, Vespa basalis, is one of the most dangerous species of wasps found in Taiwan. The insect is aggressive and its venom is highly toxic. By gel filtration on a Fractogel TSK HW 50 column followed by cation-exchange chromatography on CM-Trisacryl M, a lethal protein was purified from the venom. It has a molecular mass of about 32 kDa and an i.v. LD50 value of 0.32 micrograms/g mouse. The toxin is capable of catalyzing the hydrolysis of emulsified phospholipids but not sphingomyelin. Analysis of the 1H-NMR spectra of the substrates and its hydrolytic products revealed that the toxin liberates fatty acid from the 1-position of sn-3-phosphoacylglycerols. This result indicates that the toxin possesses phospholipase A1 activity. The toxin exhibits an extremely potent hemolytic activity in washed red cells and diluted whole blood (HC50 = 0.09 micrograms/ml in mouse). The potency of direct hemolysis is about 100-times that of a basic phospholipase A2 from Naja nigricollis venom and about 1000-times that of a cardiotoxin from Naja naja atra venom. A positive correlation between the hemolytic activity and lethality of the toxin was found in three species of animals (mouse, rat and guinea pig). In the in vivo study, the toxin caused a marked increase in the plasma K+ concentration and a hyperkalemic change in the ECG of the treated rat. Hyperkalemia resulting from the hemolytic action of the toxin appears to be the main cause of death in the animal.

Reversible neuromuscular blocking action of carboxymethylated alpha-bungarotoxin.

Carbamidomethylation of the reduced Cys29-Cys33 bridge of alpha-bungarotoxin (Bungarus multicinctus postsynaptic neurotoxin) did not alter the LD50 or irreversibility of the toxin, while carboxymethylated alpha-bungarotoxin was less potent and its neuromuscular blocking action in mouse diaphragm was reversible. The circular dichroic spectra of both modified toxins were similar but slightly different from that of native toxin. Neuromuscular transmission in the chick biventer cervicis nerve-muscle preparation could be blocked by the carboxymethylated toxin, and reactivated by washing, whereas the response of the muscle to extrinsic acetylcholine could also be blocked but was hardly restored by washing. These results suggest that carboxymethylated toxin can differentiate between junctional and extrajunctional acetylcholine receptors in chick skeletal muscle.

Synthesis of a fully active snake venom cardiotoxin by fragment condensation on solid polymer.

A polypeptide cardiotoxin containing 60 amino acids with 4 disulfide bonds has been synthesized by the "fragment solid-phase" method. The identity of the synthetic product with native cardiotoxin was established by chromatography on Sephadex G-50, carboxymethyl-cellulose column chromatography, thin layer chromatography, disc gel electrophoresis, amino acid analysis, end group analysis, peptide mapping, circular dichroism spectra, and four biological tests.

Renaturation of a reduced Taiwan cobra cardiotoxin.

Refolding of a denatured protein obtained by reducing cardiotoxin from the Taiwan cobra with mercaptoethanol has been carried out in aqueous and non-aqueous solutions. Oxidation of the reduced protein in 0.05 M phosphate buffer (pH 7.2) resulted in isolating an active protein which showed, as compared to native cardiotoxin, identical conformation and biological activities such as lethality, antigenicity and muscle contracture inducing activity. On the other hand, the reduced protein was undergoing incorrect SS-pairing and several inactive products were formed in a mixture of 1,2-ethanediol and 1-propanol (1 : 1; v/v).

Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder.

In vitro experiments have demonstrated that epidermal growth factor (EGF)-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities. The implications of cross-talk among ErbB family receptors in human cancer, however, remain to be clarified. This cohort study was performed to examine the expression patterns of ErbB receptors by immunohistochemistry in primary human bladder cancer (n = 245) and compared with conventional biological indicators for their prognostic significance. Expression of individual EGF receptor (EGFR) and ErbB2, ErbB3, or ErbB4 receptors was detected in 72.2, 44.5, 56.3, and 29.8% of bladder cancer cases, respectively. Expression of two of the receptors varied from 14.7 to 42.4%, of three of the receptors between 11.0 and 22.0%, and of all four of the ErbB receptors by 8.6%. Important indicators in association with patient survival were tumor staging (P = 0.017), ErbB2 (P = 0.018), EGFR-ErbB2 (P = 0.023), and ErbB2-ErbB3 (P = 0.042). In the subset of grade-2 tumors, EGFR-ErbB2-ErbB3 and EGFR-ErbB2 predicted the development of second recurrence (P = 0.026 and 0.039, respectively), and ErbB2-ErbB3 tended to correlate with patient survival (P = 0.09). The results indicate that a combination of EGFR, ErbB2, and ErbB3 expression profile may be a better prognostic indicator than any family member alone. Given that ErbB2 is the preferred coexpression partner of ErbB family members, expression of other ErbB receptors may significantly affect the prognostic implication of ErbB2 for bladder cancer patients.

Molecular defense response of oil palm to Ganoderma infection.

Basal stem rot (BSR) of oil palm roots is due to the invasion of fungal mycelia of Ganoderma species which spreads to the bole of the stem. In addition to root contact, BSR can also spread by airborne basidiospores. These fungi are able to break down cell wall components including lignin. BSR not only decreases oil yield, it also causes the stands to collapse thus causing severe economic loss to the oil palm industry. The transmission and mode of action of Ganoderma, its interactions with oil palm as a hemibiotroph, and the molecular defence responses of oil palm to the infection of Ganoderma boninense in BSR are reviewed, based on the transcript profiles of infected oil palms. The knowledge gaps that need to be filled in oil palm-Ganoderma molecular interactions i.e. the associations of hypersensitive reaction (HR)-induced cell death and reactive oxygen species (ROS) kinetics to the susceptibility of oil palm to Ganoderma spp., the interactions of phytohormones (salicylate, jasmonate and ethylene) at early and late stages of BSR, and cell wall strengthening through increased production of guaiacyl (G)-type lignin, are also discussed.

Elucidation of the solution structure of cardiotoxin analogue V from the Taiwan cobra (Naja naja atra)--identification of structural features important for the lethal action of snake venom cardiotoxins.

The aim of the present study is to understand the structural features responsible for the lethal activity of snake venom cardiotoxins. Comparison of the lethal potency of the five cardiotoxin isoforms isolated from the venom of Taiwan cobra (Naja naja atra) reveals that the lethal potency of CTX I and CTX V are about twice of that exhibited by CTX II, CTX III, and CTX IV. In the present study, the solution structure of CTX V has been determined at high resolution using multidimensional proton NMR spectroscopy and dynamical simulated annealing techniques. Comparison of the high resolution solution structures of CTX V with that of CTX IV reveals that the secondary structural elements in both the toxin isoforms consist of a triple and double-stranded antiparallel beta-sheet domains. Critical examination of the three-dimensional structure of CTX V shows that the residues at the tip of Loop III form a distinct "finger-shaped" projection comprising of nonpolar residues. The occurrence of the nonpolar "finger-shaped" projection leads to the formation of a prominent cleft between the residues located at the tip of Loops II and III. Interestingly, the occurrence of a backbone hydrogen bonding (Val27CO to Leu48NH) in CTX IV is found to distort the "finger-shaped" projection and consequently diminish the cleft formation at the tip of Loops II and III. Comparison of the solution structures and lethal potencies of other cardiotoxin isoforms isolated from the Taiwan cobra (Naja naja atra) venom shows that a strong correlation exists between the lethal potency and occurrence of the nonpolar "finger-shaped" projection at the tip of Loop III. Critical analysis of the structures of the various CTX isoforms from the Taiwan cobra suggest that the degree of exposure of the cationic charge (to the solvent) contributed by the invariant lysine residue at position 44 on the convex side of the CTX molecules could be another crucial factor governing their lethal potency.

Translation initiation and assembly of peripherin in cultured cells.

The peripherin gene has three potential ATG translation initiation sites at positions 38, 56, and 290. The second ATG has been proposed to be the initiation codon used for translation of the protein, but there is no experimental evidence for this conjecture. We have isolated a full-length peripherin cDNA (designated as p61-11) from a rat brain cDNA library. Upon sequencing, we found that this cDNA contains a point mutation at the second potential translation initiation codon, which changes this ATG to ACG. When expressed in SW13 cl.2 vim- cells, a cell line without any detectable cytoplasmic intermediate filaments, the protein product of p61-11 cannot form a filamentous network and the major product is 45 kDa in size, which is most likely initiated from the third ATG. The protein product from the first ATG (57 kDa in size) of p61-11 is also detected albeit in smaller amounts. We introduced a frame-shift mutation upstream of the third ATG in p61-11 to create p61-11FS and showed that the third ATG is able to initiate translation efficiently even in the presence of the first ATG, and the 45 kDa protein leads to a diffuse nonfilamentous staining pattern in vim- cells confirming that the first ATG may not be the preferred translation initiation codon, since it cannot suppress a downstream ATG. We increased the translation efficiency from the first ATG of p61-11 by mutating the three nucleotides preceding this first ATG and thereby placing it in a better Kozak consensus sequence for translation initiation. The resulting 57 kDa protein is able to form a filamentous network in vim- cells. We corrected the mutation in the original p61-11 by polymerase chain reaction and generated two peripherin constructs: perM1M2 (which contains all three translation initiation codons) and per delta 1M2 (the first ATG is deleted, but the other two are present). When transfected, their protein products, about 57 kDa in size, form filamentous networks in the absence of other cytoplasmic intermediate filaments. Since there is no 45 kDa protein detected for these latter two constructs, it is reasonable to conclude that in the presence of the second ATG, little or no translation is initiated from the third ATG. Taken together, these results strongly suggest that the second ATG is the preferred translation initiation codon for the peripherin gene.