Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Antibacterial activity of viable and heat-killed probiotic strains against oral pathogens.

Probiotics can stabilize gut flora, regulate intestinal immunity and protect the host from enteric diseases; however, their roles in oral health have received little attention compared to their roles in gut health. Nowadays, the prevalence of sugar-sweetened foods and abuse of antibiotics contribute towards dysbiosis of oral microbiota and drug resistance development in oral pathogens, resulting in various intractable oral diseases. We screened the antibacterial activities of viable and heat-killed probiotic strains against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. The probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 displayed strong antipathogenic activities, whereas heat-killed AP-32, CT-53 and ET-66 displayed high levels of pathogen inhibition. The antibacterial activities of these probiotics were not associated with their H2 O2 production; L. acidophilus TYCA02 produced high levels of H2 O2 but merely exhibited moderate antibacterial activities. Oral tablets containing probiotics showed positive inhibitory effects against oral pathogens, particularly those containing viable probiotics. Our results indicate that probiotics prevent the growth of oral pathogens and improve oral health, providing insights into the antipathogenic efficacy of different probiotic species and their potential role in functional foods that improve oral health. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides insights into the antipathogenic efficacy of different probiotic species and their potential roles in developing functional foods to improve oral health. We showed that the probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 have great potential for use in the development of functional foods to improve oral health. Since active probiotics may provide strong and long-term protection, the development of functional food products should favour the use of viable bacteria.

Polymer-free biolimus-A9-coated stent for primary percutaneous coronary intervention.

BACKGROUND: The polymer-free biolimus-A9 drug-coated stent (DCS) was reported to have superior safety and efficacy outcomes compared with a bare metal stent in the LEADERS FREE trial of high-bleeding-risk patients with acute coronary syndrome and on dual antiplatelet treatment (DAPT) for 1 month. The aim of this investigation was to evaluate the DCS in a consecutive cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We analyzed data from 164 consecutive STEMI patients who underwent PPCI using the DCS at our institution. The primary efficacy endpoint was clinically indicated target lesion revascularization (ciTLR); the primary safety endpoint was a composite of cardiac death, myocardial infarction, and definite/probable stent thrombosis. Clinical outcomes at 1 year are presented here. RESULTS: The mean age of the patients was 61.5 ± 15.5 years, and 86.6% were male. The median symptom-to-balloon-time was 55 min. In 57.9% of patients (n = 95), the infarct had an anterior location. PPCI achieved Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 163 of 164 patients (99.4%). All patients were prescribed DAPT for 1 year. At 1 year, ciTLR occurred in 1.2% of patients, the primary safety endpoint was reached in 4.3% of patients, and definite stent thrombosis was noted in 0.6% of patients. CONCLUSION: In this consecutive real-world cohort of patients, the DCS was safe and efficacious when used for PPCI in patients with STEMI.

Treatment with 48-mm everolimus-eluting stents : Procedural safety and 12-month patient outcome.

BACKGROUND: Lesion length is a major predictor of adverse outcomes after percutaneous coronary intervention. Long lesions often require multiple stents with variable overlap, which increases the probability of geographical miss and the incidence of mechanical complications, such as side-branch occlusion, restenosis, and stent thrombosis. These pitfalls may be avoided by use of an ultra-long device. METHODS: We retrospectively assessed the performance of the 48-mm Xience Xpedition everolimus-eluting stent (EES) at our institution. RESULTS: A total of 123 patients (mean age: 60.94 years, n = 93 [76%] male) with 129 lesions were identified. Lesions (n = 69, 53.5%) were located in the left anterior descending artery, the right coronary artery (n = 47, 36.4%), and the circumflex artery (n = 8, 6.2%); 83 lesions involved a major side branch. The majority were treated with a provisional single-stent strategy. Other characteristics included significant tortuosity in 15 lesions (11.6%) and moderate-to-heavy calcification in 46 lesions (35.7%). In all cases, balloon pre-dilatation was performed before stent insertion. Successful delivery and deployment of the 48-mm EES device was achieved in 100% of the patients. The mean number of stents per lesion was 1.4, while the mean total stent length was 58 ± 17.3 mm and mean stent diameter, 3.00 ± 0.67 mm. The procedural success rate was 99.2%. The 30-day major cardiac adverse event (MACE) rate was 0.8%, while the 12-month MACE was 3.3%. CONCLUSION: The Xience 48-mm EES device appears to be safe and efficacious with a low clinical event rate at the 12-month follow-up. Where feasible, this would support the use of the ultra-long 48-mm platform in lieu of multiple overlapping shorter devices.

Distal longitudinal deformation of a Synergy stent by jailed Rotawire guidewire.

Recent advances in stent technology have led to the development of thin strut platforms with fewer connectors. This has improved delivery but compromised strength, as illustrated by recent cases of longitudinal compression. We present an unusual case of longitudinal shortening at the distal end of a Synergy stent.

Safety of bailout stenting after paclitaxel-coated balloon angioplasty.

BACKGROUND: Bailout stenting after suboptimal paclitaxel-coated balloon (PCB) angioplasty is required in up to 28% of cases. We sought to compare the safety of bailout stenting with drug-eluting stents (DES) compared with the more established combination of PCB with bare metal stents (BMS). METHODS: We retrospectively evaluated all patients who had stents implanted owing to suboptimal PCB angioplasty results between January 2010 and April 2015. Endpoints analyzed were major adverse cardiac events (MACE) - defined as cardiovascular death, nonfatal myocardial infarction (MI), and target lesion revascularization (TLR) - as well as major and minor bleeding. RESULTS: Baseline clinical characteristics were comparable with a high proportion of diabetics in both groups (50.0% vs. 45.8%, p = 0.74). BMS and DES sizes were similar (mean diameter 2.72 ± 0.50 mm vs. 2.89 ± 0.56 mm, p = 0.20, length 25.22 ± 13.47 mm vs. 28.08 ± 9.08 mm, p = 0.47). Outcomes were comparable at the end of 1 year (MACE 12.2% vs. 9.5%, p = 1.00, TLR 6.1% vs. 4.8%, p = 1.00, MI 0% vs. 4.8%, p = 0.30). There was no case of stent thrombosis or major bleeding, and the rates of minor bleeding were similar (4.2% vs. 4.8%, p = 1.00). CONCLUSION: Our initial experience using DES instead of BMS as a bailout after suboptimal PCB results shows that the procedure is safe and effective at 1 year.

Storage Rot of Dragon Fruit Caused by Gilbertella persicaria.

In October 2011, a new disease of dragon fruit (Hylocereus costaricensis) was discovered in a fruit market in Yuanjiang, Yunnan Province, China. Small, light brown, water-soaked spots appeared initially and then coalesced, extending to the entire fruit in 6 days. Hyaline hyphae and light brown sporangia were observed over the entire surface of the infected fruit. On potato sucrose agar (PSA) the fungus produced a white, appressed colony that covered a 9-cm diameter petri dish in less than 5 days at 25°C. The sporangiophores were hyaline, light brown to grayish, 44.71 to 143.14 (average = 85.10) µm long, and arose directly from the non-septate substrate hyphae. The sporangia were spherical, single, and terminal and yellow-brown to brown when young turning to dark brown or black at maturity. Both the sporangiophores and sporangia were covered with calcium oxalate crystals. When mounted in a drop of water, the sporangium immediately broke longitudinally into two halves, releasing the spores and exposing a large pyriform columella at the tip of the sporangiophore. The spores were mostly globose to ellipsoid, aseptate, and 5.15 (3.71 to 7.86) × 6.30 (4.08 to 9.19) µm (n = 300). Two to three slender, hyaline appendages were attached to the ends of the spores. The cardinal growth temperatures of the pathogen were 10, 30, and 40°C and it grew faster in the dark than under 12-h alternating light-dark cycles. The fungus was identified as Gilbertella persicaria (1). To confirm the identification, the internal transcribed spacer region of the nuclear rDNA of one isolate was amplified using the fungal primers ITS1 and ITS4. The nucleotide sequence (Accession No. JQ951601) showed 98% homology with G. persicaria in GenBank (HM999958). Pathogenicity tests were carried out on two species of dragon fruit, H. costaricensis and H. undatus, by placing a 6-mm diameter young mycelial PSA agar disc on the surface of an asymptomatic fruit, either unwounded or wounded with a sterile needle. As the control, a plain PSA disc was used. Each inoculated fruit was placed in a moist chamber and incubated at 25°C. Three fruits were used per treatment and the experiment was repeated twice. The fruits rotted in 2 to 3 days, and the disease was especially serious on wounded fruits and on H. costaricensis. The fungus was reisolated from infected fruits. The controls did not show any disease symptoms. Inoculation studies were also made on other fruits but rot was produced only on peach, pear, and wounded tomato. To our knowledge, this is the first record of dragon fruit rot caused by G. persicaria. The fungus had been reported in China but caused no diseases (2). In India, it caused fruit rot of pear, tomato, and peach (3). To minimize the disease, dragon fruit should be stored at low temperature and in uncovered containers. References: (1) G. L. Benny. Mycologia 83:150, 1991. (2) J. Y. Cheng and H. Y. Mei. Acta Phytotax. Sin. 10:105, 1965. (3) M. D. Mehrotra. Mycopath. Mycol. Appl. 29:151, 1966.

First Report of Ralstonia solanacearum Causing Bacterial Wilt of Yacon in China.

Yacon (Smallanthus sonchifolius) is an important cash crop in Yunnan Province, China. In 2003, yacon was introduced to Yunnan province as a novelty root crop and as an experimental source of natural sugars; now more than 15 provinces cultivate the crop. Yunnan is one of the major yacon producing areas of China, with up to 10,000 ha yielding up to 50,000 t of yacon, which is nearly half of the production in China. In April and May 2010, bacterial wilt of yacon was observed in the fields of Lion Mountain of Wuding County, Yunnan Province, China. In 2011, the disease occurred in approximately 1 ha of yacon, resulting in 10% crop loss in that area. The initial symptoms observed were irregular, black, necrotic lesions on leaf margins. After 4 to 7 days, leaves became totally necrotic, plants wilted, and black stripes were observed on plant stems. Within 2 to 3 weeks, more than 70% of leaves within the crop were wilted. Subsequently, the plants died and stems became brittle. When dead plants were pulled from the soil, tubers were found to have turned black. When diseased stems and/or petioles were cut with a sterile sharp knife or razor blade, bacterial ooze appeared on the cut ends. High populations of morphologically uniform bacteria were isolated from the diseased plants by conventional methods. When cultured on TZC (2,3,5-Triphenylte tetrazolium chloride) agar medium (3), colonies were large, elevated, fluidal, and entirely white with a pale red center. The isolated bacterium was gram-negative, grew aerobically, and did not form endospores. The cells were 0.5 to 0.7 × 1.5 to 2.0 µm and nonencapsulated. Ralstonia solanacearum was identified and confirmed as the pathogen on the basis of morphological and physiological characteristics, pathogenicity test, and 16S rDNA sequence analysis (1,4). The nucleotide sequence is available in GenBank (Accession No. HQ176322.1). The pathogenic strain belonged to race 1 and biovar 3 according to the pathogenicity and carbohydrate utilization tests (2). Koch's postulates were tested in the greenhouse, with 10 plants inoculated per species. Plants were inoculated with 15 µl of cell suspension containing 106 to 107 CFU ml-1 deposited into the third axilla with a capillary tube. The bacteria could infect tomato, pepper, tobacco, potato, common sage (Salvia dugesii Fernald), and patchouli, and caused typical symptoms of wilt and black lesions, but could not infect leaves of swamp mahogany (Eucalyptus robusta Smith), stramonium (Dature stramonium Datura L.), ginger, or maize. To our knowledge, this is the first report of yacon as a host of R. solanacearum. Since the pathogen has a wide host range, monitoring of the vegetation in and around yacon fields should be implemented as a mandatory management measure to prevent disease spread. References: (1) C. A. Boucher et al. J. Bacteriol. 169:5626, 1987. (2) A. C. Hayward. J. Appl. Bacteriol. 27:265, 1964. (3) A. Kelman. Phytopathology 44:693, 1954. (4) W. G. Weisburg et al. J. Bacteriol. 173:697, 1991.

Peri-operative management of anti-platelet agents and anti-thrombotic agents in geriatric patients undergoing semi-urgent hip fracture surgery.

Hip fractures are common events in the geriatric population and are often associated with significant morbidity and mortality. Over the coming decades, the size of the greying population is forecast to increase and hence, the annual incidence of hip fracture is expected to rise substantially. Several studies have shown that hip fracture surgery performed within 24 to 48 h of hospitalisation significantly reduces mortality. Medical specialists including cardiologists are often involved in the care of these geriatric patients as most of them have comorbid conditions that must be managed concomitantly with their fracture. Cardiovascular and thromboembolic complications are among some of the commonest adverse events that could be experienced by these elderly patients during hospitalisation. We review in this article the current recommendations and controversies on the peri-operative management of anti-platelet agents and anti-thrombotic agents in geriatric patients undergoing semi-urgent hip fracture surgery.

Monitoring and assessing variation of sewage quality and microbial functional groups in a trunk sewer line.

In this study, the variation of sewage quality was investigated and the active fraction of different microbial functional groups in biofilm was quantified in a 5.6-km trunk sewer line. The sewage quality including suspended solids, biochemical oxygen demand, total chemical oxygen demand (COD), total nitrogen, total Kjeldahl nitrogen, ammonia nitrogen, nitrite nitrogen, and nitrate nitrogen were measured and compared with the values in literatures. The results indicated that since the wastewater treatment plant was not operated at its full capacity, the concentrations of different compounds were lower compared with the values in literatures. The values of heterotrophic growth rate constant lay between 5.6 and 8.6 day(-1). Its average value was 7.7 day(-1). The values of heterotrophic lysis rate constant lay between 0.2 and 0.4 day(-1). The active heterotrophic biomass in biofilm varied from 240 to 800 mg COD m(-2) and average value was 497 mg COD m(-2). The biofilm mass varied from 880 to 1,080 mg m(-2). The percentage of heterotroph to biofilm mass fall within the range of 24.0-90.9% and average value was 52.9%. In the oxygen uptake rate batch tests, the biomass, growth rate constant, and lysis rate constant of autotroph could not be determined because the fraction of autotroph in biofilm was relatively few. It revealed that the degradation of organic matters, nitrification, and denitrification occurred in the trunk sewer line. But the results indicate that the condition seem favorable for nitrification.

A transmembrane polymorphism in FcgammaRIIb (FCGR2B) is associated with the production of anti-cyclic citrullinated peptide autoantibodies in Taiwanese RA.

The aim of the current study was to determine whether the FcgammaRIIb 187-Ile/Thr polymorphism is a predisposition factor for subtypes of RA defined by disease severity and production of autoantibodies against cyclic citrullinated peptides (anti-CCPs) in Taiwanese RA patients. Genotype distributions and allele frequencies of FcgammaRIIb 187-Ile/Thr were compared between 562 normal healthy controls and 640 RA patients as stratified by clinical parameters and autoantibodies. Significant enrichment of 187-Ile allele was observed in RA patients positive for anti-CCP antibodies as compared with the anti-CCP negative RA patients (P=0.001, OR 1.652 (95% CI 1.210-2.257)) or as compared with the normal controls (P=0.005, OR 1.348 (95% CI 1.092-1.664)). In addition, 187-Ile allele was found to be enriched in RA patients positive for rheumatoid factor (RF) compared to the RF negative RA patients (P=0.024, OR 1.562 (95% CI 1.059-2.303)). Furthermore, the homozygotes were enriched in destructive male RA patients (P=0.035; OR 2.038 (95% CI 1.046-3.973)) and the 187-Ile allele was associated with early-onset of RA in Taiwanese patients (P=0.045, OR 1.548 (95% CI 1.007-2.379)). Thus, FcgammaRIIb SNP 187-Ile/Thr may influence the RA phenotypes in Taiwanese RA.

Tubulin-dependent hydrolysis of guanosine triphosphate as a screening test to identify new antitubulin compounds with potential as antimitotic agents: application to carbamates of aromatic amines.

Tubulin-dependent GTP hydrolysis was evaluated for its potential as a relatively simple screening assay for new antimitotic drugs. Carbamates of aromatic amines were chosen as the test system because of the relatively diverse structures of compounds in this class already known to have antimitotic properties and because of the large number of such compounds in the NSC collection of the National Cancer Institute. Of 162 compounds evaluated, significant alterations in the GTPase reaction were observed with 26 agents. Sixteen of these had substantial inhibitory effects on tubulin polymerization (true positives), while ten did not (false positives). There were no false negatives (i.e., no agent inactive in the GTPase assay inhibited tubulin polymerization). The true positives were examined for effects on cell growth and mitosis, and four compounds had 50% inhibitory concentration values of 2 microM or less with L1210 murine leukemia cells. All four caused the accumulation of cells in metaphase arrest. We conclude that tubulin-dependent GTP hydrolysis can be used effectively to select new antitubulin compounds with potential as antimitotic agents from a large group of compounds of unknown activity.

Cornigerine, a potent antimitotic Colchicum alkaloid of unusual structure. Interactions with tubulin.

Cornigerine is a natural product analog of colchicine produced by Colchicum cornigerum in which the vicinal 2- and 3-methoxy groups are condensed into a methylenedioxy bridge. This produces a fourth ring and a structure which resembles a hybrid of colchicine, podophyllotoxin, and steganacin. Cornigerine was somewhat more toxic than colchicine with L1210 murine leukemia cells and caused them to accumulate in metaphase arrest. Cornigerine resembled colchicine in its interactions with tubulin in vitro, and it was also somewhat more potent than colchicine in these drug-tubulin interactions. Cornigerine inhibited tubulin polymerization both with and without microtubule-associated proteins, inhibited the binding of radiolabeled colchicine to tubulin, and stimulated tubulin-dependent GTP hydrolysis. Indirect evidence suggested that the binding of cornigerine to tubulin is relatively slow and temperature-dependent, like the binding of colchicine to the protein.

Speed of stress wave propagation in lung.

The speed of stress waves in the lung parenchyma was investigated to understand why, among all internal organs, the lung is the most easily injured when an animal is subjected to an impact loading. The speed of the sound is much less in the lung than that in other organs. To analyze the dynamic response of the lung to impact loading, it is necessary to know the speed of internal wave propagation. Excised lungs of the rabbit and the goat were impacted with water jet at dynamic pressure in the range of 7-35 kPa (1-5 psi) and surface velocity of 1-15 m/s. The stress wave was measured by pressure transducer. The distance between the point of impact and the sensor at another point on the far side of the lung and the transit time of the stress wave were measured. The wave speed in the goat lung was found to vary from 31.4 to 64.7 m/s when the transpulmonary pressure Pa-Ppl was varied from 0 to 20 cmH2O where Pa represents airway pressure and Ppl represents pleural pressure. In rabbit lung the wave speed varied from 16.5 to 36.9 m/s when Pa-Ppl was varied from 0 to 16 cmH2O. Using measured values of the bulk modulus, shear modulus, and density of the parenchyma, reasonable agreement between theoretical and experimental wave speeds were obtained.

Cerebral infarction in perinatal and childhood bacterial meningitis.

BACKGROUND: Cerebral infarction is an important neurological complication of childhood bacterial meningitis, but little is known about its epidemiology and outcomes. AIM: To determine the predictive factors, clinical features, causative pathogens, and outcomes of cerebral infarction secondary to perinatal and childhood bacterial meningitis. DESIGN: Retrospective analysis METHODS: Over the period 1986-2001, 166 perinatal and childhood patients were identified as having culture-proven bacterial meningitis, of whom 14 had cerebral infarction at admission. The clinical and CSF data of patients with and without cerebral infarctions on admission were compared. RESULTS: Cerebral infarction patients accounted for 10% (14/166) of bacterial meningitis cases, mostly in the first year of life (11/14, 79%). Salmonella species (n = 4) and Streptococcus pneumoniae (n = 4) were the most frequent causative pathogens, accounting for 57% (8/14) of episodes. Single infarctions were found in four patients and multiple infarctions in 10. At 1 year follow-up, outcome was good in three, but poor in 11. Significant differences between the two patient groups at admission included age bands, presence of seizures, hydrocephalus, disturbed consciousness on admission, and CSF lactate concentration. DISCUSSION: There was a high prevalence of cerebral infarctions when the disease was caused by S. pneumoniae and Salmonella species. Occurrence was highest in the first year of life, and the prognosis in this patient group is poor. Risk factors associated with cerebral infarction in our patients included age 28-365 days, seizures, hydrocephalus, disturbed consciousness on admission, and high CSF lactate concentrations.

Subtypes of autism by cluster analysis.

Multidisciplinary data from 166 children with autistic spectrum disorders were subjected to cluster analysis. Cross-validation between random halves of the sample showed acceptable consistency of the clustering method. Four clinically meaningful subtypes emerged from the analysis. They did not differ in demographic characteristics but did show, on average, distinct differences in behavioral and cognitive areas. Over half of the sample fell into a subtype described as typically autistic with abnormal verbal and nonverbal communication, aloofness, impaired social skills, and sensory disturbances. Another 19% were similarly autistic but with moderate to severe mental handicap. The remaining children formed two subtypes: a high-functioning Asperger-like group who were overactive and aggressive, and a small group who were impaired in social and language skills, had restricted interests, and a family history of learning problems. This study highlights important differences among children with autism and emphasizes relationships between cognitive functioning and subtypes of the disorder.

Clinical characteristics of juvenile rheumatoid arthritis in Taiwan.

This study aimed to investigate the clinical features of juvenile rheumatoid arthritis among Taiwan children. The medical records of 228 children who had juvenile rheumatoid arthritis treated in the Chang Gung Medical Center in Taiwan from 1978 through 1998 were retrospectively reviewed. A total of 146 boys and 82 girls (M:F ratio, 1.8:1) were included in this study. Clinical and laboratory data of these patients were collected from medical charts. Pauciarticular onset (56%) was the most common type of juvenile rheumatoid arthritis, followed by polyarticular (36%) and systemic (8%) type. The positive rate for rheumatoid factor, human leukocyte antigen B27, and antinuclear antibody were 9.2%, 55.2%, and 16.2%, respectively. Uveitis was observed in 5.7% of patients. Compared with previous reports in other regions and populations, remarkably different features of juvenile rheumatoid arthritis were found in this study, which included a higher prevalence among boys than girls, a high positive rate of human leukocyte antigen B27, and a low rate of uveitis.

The correlates of depressed mood in adolescents in Hong Kong.

PURPOSE: Most studies of depressed mood and its correlates in adolescents have been conducted in Western countries. This study examined the relationship between a broad range of stressors and depressed mood in a community sample of Hong Kong adolescents. METHODS: Secondary school students (n = 996) completed the Chinese Beck Depression Inventory (C-BDI), provided demographic information, and indicated their perceptions of family and peer relationships, school function and pressures, and subjective health, and some measures salient to the Hong Kong environment: triad gang pressure, religiosity, and intent to emigrate. The correlation between C-BDI and these variables was assessed in bivariate and multivariate analyses. RESULTS: Hong Kong adolescents reported higher levels of depressive symptoms than a comparison group of Western teenagers. Girls showed more symptoms than boys. All stressors correlated in bivariate analyses with C-BDI, indicating similar influences on depressed mood in Western and Hong Kong teenagers. In multivariate analyses, the stressors contributed cumulatively to the C-BDI score. Perceptions of a lack of parental understanding and peer acceptance appeared as the strongest variables in predicting depressed mood. CONCLUSIONS: Depressed mood is highly prevalent among Hong Kong teenagers. Stressors play a cumulative role in their relationship to mood. Our findings point to the importance of broad screening of this vulnerable population.