Epidemiology and clinical characteristics of invasive mould infections: A multicenter, retrospective analysis in five Asian countries.

Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 µg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 µg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 µg/ml for ceftobiprole and 1 µg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 µg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 µg/ml, the MIC90 values were 2 µg/ml for teicoplanin, 0.5 µg/ml for daptomycin, and 0.5 µg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 µg/ml (2, 0.06, and 0.12 µg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 µg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

Abstracting data from medical examiner/coroner reports: concordance among abstractors and implications for data reporting.

The purpose of this study was two-pronged: 1) to determine the level of concordance (agreement) between multiple records abstractors who extracted defined data elements from printed medical examiner/coroner (ME/C) death investigation records; and 2) to identify data items for which improved reporting could facilitate the effective use of ME/C reports and data. Four hundred ninety four printed death investigation records were obtained from 224 medical examiner/coroner offices throughout the United States. Trained abstractors were asked to extract information for 110 data elements from investigative reports. Additional data elements for each toxicology workup were abstracted from toxicology laboratory reports and six-digit AIS codes were also abstracted for each injury as described in autopsy reports. The ability of multiple abstractors to identify each data element and identically abstract the data was assessed using Kappa statistical methods. Level of agreement for many data elements was very good (>0.9), but for some data elements agreement was marginal to poor, especially for items related to toxicology, the nature of specific injuries, and dates, times of the occurrence of death and injury. Many data items can be easily abstracted from ME/C records. However, some data items seem difficult to abstract reliably in all cases. Standardizing the report formats used by ME/Cs and/or standardizing the electronic storage of ME/C data would make the abstraction of such data easier and improve the usefulness of ME/C data.

Essential role of mitogen-activated protein kinase pathway and c-Jun induction in epidermal growth factor-induced gene expression of human 12-lipoxygenase.

The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kinase (JNK) in a time-dependent manner. Treatment of the cells with an mitogen-activated protein kinase kinase inhibitor, PD098059 (30 microM), inhibited the EGF- and pSV2ras-induced expression of 12-lipoxygenase mRNA. Transfection of the cells with Ras, ERK2, Rac, JNK dominant negative mutants pMMrasDN, K52R ERK2, RacN17, and mJNK all inhibited the EGF-induced promoter activation of the 12-lipoxygenase gene. EGF induced the expression of c-Jun and the activity of transcription factor activator protein 1 in cells, and these effects were blocked by the treatment with K52R ERK2 and mJNK. Overexpression of c-Jun increased the expression of 12-lipoxygenase mRNA and enzyme activity. Furthermore, the Sp1-binding sites in the promoter region of the 12-lipoxygenase gene were requisite for c-Jun response, which was similar to that previously observed in EGF response. The results indicate that the EGF-induced expression of 12-lipoxygenase in A431 cells was mediated through the Ras-ERK and Ras-Rac-JNK signal pathways. Subsequent induction of c-Jun led by ERK and JNK activation was essential for this EGF response.

Double phase conjugation with orthogonally polarized beams in a BaTiO(3) crystal.

We have demonstrated experimentally the simultaneous self-conjugation of extraordinarily and ordinarily polarized light waves (lambda=514 nm), with the polarization state preserved, in a Ce:BaTiO(3) crystal. Conjugate o waves originate from coupling between o and e waves by means of a circular photogalvanic effect. The conjugator also takes advantage of the Ce:BaTiO(3) crystal, for which it is easy to generate an extraordinary conjugate beam by photorefractive backscattering. This beam of light is necessary for double phase conjugation.

Purification of thymine glycol DNA and nucleosides by use of boronate chromatography.

Boronate columns can be used to purify DNAs containing cis-thymine glycol residues and can also be used to purify cis-thymine glycol nucleosides. The boronate group can form a reversible complex with the cis-diol of the thymine glycol but not with the urea residue which is formed by alkaline hydrolysis of the thymine glycol. This method is rapid and appears applicable to a range of nucleic acids. In addition to the purifications of DNAs and nucleosides demonstrated here boronate chromatography may be applicable to assaying the extent and sites of oxidative damage to DNAs.

Asian or Pacific Islander mortality, selected states, 1992.

OBJECTIVES: In this report the National Center for Health Statistics (NCHS) presents mortality data in greater race detail than has previously been presented for the Asian or Pacific Islander (API) population. METHODS: Deaths, estimated death rates, age-adjusted death rates, exploratory life expectancies, and ranking of leading causes are presented for a selected area. RESULTS: In 1992 a total of 19,478 deaths occurred in the Asian or Pacific Islander population in the seven States examined in this report. Heart disease and cancer were the two leading causes of death for each of the Asian or Pacific Islander subgroups. By age there is striking variation in leading causes among the race groups. Among the API subgroups in these States, age-adjusted death rates are greatest for the Samoan and Hawaiian populations and smallest for the Asian Indian, Korean, and Japanese populations. Life expectancy is lowest for the Hawaiian and Samoan populations.

In vitro repair of oxidative DNA damage by human nucleotide excision repair system: possible explanation for neurodegeneration in xeroderma pigmentosum patients.

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

Structure of a duplex DNA containing a thymine glycol residue in solution.

Oxidative stress, ionizing radiation, and other events can induce the oxidation of the thymine in DNA to thymine glycol. The presence of thymine glycol can have significant biological consequences, and there are specific repair enzymes for thymine glycol in a wide range of organisms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combined use of NMR and restrained molecular dynamics. The duplex of d(C1G2C3G4A5Tg6A7C8G9C10C11) paired with d(G22C21G20C19T18A17T16G15C14G13G12), with Tg indicating thymine glycol, has been used for these studies. The structure shows that the thymine glycol induces a significant, localized structural change with the thymine glycol largely extrahelical. This structural information is consistent with the biological consequences of thymine glycol in DNA. This structure is compared with that of a DNA duplex with an abasic site in the same sequence context.

Purification of a mammalian homologue of Escherichia coli endonuclease III: identification of a bovine pyrimidine hydrate-thymine glycol DNAse/AP lyase by irreversible cross linking to a thymine glycol-containing oligoxynucleotide.

We purified a homologue of the Escherichia coli DNA repair enzyme endo nuclease III 5000-fold from calf thymus which, like endonuclease III, demonstrates DNA-glycosylase activity against pyrimidine hydrates and thymine glycol and AP lyase activity (DNA strand cleavage at AP sites via beta-elimination). The functional similarity between the enzymes suggested a strategy for definitive identification of the bovine protein based on the nature of its enzyme-substrate (ES) intermediate. Prokaryotic DNA glycosylase/AP lyases function through N-acylimine (Schiff's base) ES intermediates which, upon chemical reduction to stable secondary amines, irreversibly cross link the enzyme to oligodeoxynucleotides containing substrate modified bases. We incubated endonuclease III with a 32P- labeled thymine glycol-containing oligodeoxynucleotide in the presence of NaCNBH3. This resulted in an increase in the apparent molecular weight of the enzyme by SDS-PAGE. Phosphorimaging confirmed irreversible cross linking between enzyme and DNA. Identical treatment of the most purified bovine enzyme fraction resulted in irreversible cross linking of the oligodeoxynucleotide to a predominant 31 kDa species. Amino acid analysis of the 31 kDa species revealed homology to the predicted amino acid sequence of a Caenorhabditis elegans 27.8 kDa protein which, in turn, has homology to endonuclease III. The translated amino acid sequences of two partial 3' cDNAs, from Homo sapiens and Rattus sp., also demonstrate homology to the C. elegans and bovine sequences suggesting a homologous family of endonuclease III-like DNA repair enzymes is present throughout phylogeny.

The abstractability and consistency of medical examiner/coroner reports: results from the 1993 National Mortality Followback Survey pilot.

UNLABELLED: The 1993 National Mortality Followback Survey (NMFS) is designed to provide national estimates of important characteristics of the 2,218,940 people aged 15 years and older who died in 1993. One topic of special interest in the survey is injury-related deaths. Previous followback surveys have not obtained data from medical examiner and coroner offices (ME/Cs), who investigate most injury-related deaths. In this study, we sought to determine the feasibility of collecting data from various ME/C offices for the NMFS and the usefulness and limitations of data derived from their records. METHODS: We 1) developed a pilot survey instrument, the Medical Examiner/Coroner Abstract (MECA); 2) attempted to collect ME/C records on 159 deaths from 55 ME/C offices in four states with a variety of death investigation systems; and 3) assessed the feasibility of abstracting data from these records using the MECA. RESULTS: We received records on 105 deaths from 39 ME/C offices in three states. We identified items that could be abstracted from the records of most deaths and found that different abstractors could reproducibly and reliably identify information on these core items. Using the results of this study, we revised the MECA for use in the NMFS.

Different effects of strenuous exercise and moderate exercise on platelet function in men.

BACKGROUND: Platelets play an important role in the pathogenesis of cardiovascular diseases. It is also noticed that on one hand, regular exercise can reduce the risk of cardiovascular diseases, and on the other hand, vigorous exercise provokes sudden cardiac death. We therefore hypothesize that various intensities of exercise may affect platelet function differently. METHODS AND RESULTS: Strenuous and moderate exercise (about 50% to 55% of peak oxygen consumption, VO2peak) on a bicycle ergometer in 10 sedentary and 10 physically active healthy young men was executed on two separate occasions. Blood samples were collected before and immediately after exercise. A newly designed tapered parallel plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured by ELISA. In addition, a similar study on 5 patients with stable angina were also conducted. Our results showed that (1) in the sedentary healthy group, platelet adhesiveness and aggregation were increased by strenuous exercise and depressed by moderate exercise; (2) in the active healthy group, platelet adhesiveness and aggregation were enhanced by severe exercise, whereas only aggregation was decreased by moderate exercise; (3) in the patients with stable angina, platelet adhesiveness and aggregation were enhanced by strenuous exercise and adhesiveness was suppressed by moderate exercise; (4) the degree of hemoconcentration induced by acute exercise tended to be related to the severity of exercise in all subjects; and (5) although severe exercise elevated beta-TG and PF4, there were no significant changes in beta-TG, PF4, and the ratio of beta-TG to PF4 in healthy subjects after exercise. CONCLUSIONS: It is concluded that platelet adhesiveness and aggregability may be sensitized by strenuous exercise in both healthy subjects and patients with stable angina. In contrast, platelet function can be suppressed significantly by moderate exercise in the healthy and tends to be depressed in patients with stable angina. The former may increase the risk of cardiac arrest and the latter may protect us from cardiovascular diseases. In addition, the effects of acute exercise tend to be more pronounced in the sedentary than in the active.

Isokinetic and isometric testing of knee musculature in young female patients with patellofemoral pain syndrome.

By using a Cybex II+ isokinetic dynamometer, we performed isokinetic and isometric tests of the knee musculature in 29 female patients (aged 17-45 years) with patellofemoral pain syndrome (PFPS) and the same number of age- and weight-matched female controls. The pain was unilateral in 11 patients and bilateral in 18. The isokinetic testing was set at speeds of 60 degrees, 120 degrees and 180 degrees/sec; the isometric testing was set at 30 degrees and 60 degrees of knee flexion. The results showed that the lowest torque values occurred on the affected side of the unilateral group, followed by both sides of the bilateral group, the sound side of the unilateral group, and the control group, sequentially. The highest rate of abnormal torque values for all PFPS patients occurred in the quadriceps at 60 degrees/sec of isokinetic contraction: 33%. In this study, five (17%) patients showed abnormal torque curves and 10 (34%) patients complained of pain or soreness at either the lowest speed of isokinetic testing or during the isometric testing of the quadriceps muscles. The bilateral torque difference was highest in the unilateral group.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition in vivo of the formation of adducts between metabolites of benzo(a)pyrene and DNA by aryl hydrocarbon hydroxylase inducers.

The lungs of A/HeJ mice are susceptible to benzo(a)pyrene (BP)-induced neoplasia whereas the livers are resistant. Following p.o. administration of a carcinogenic dose of [3H]BP, radioactivity was associated with the DNA of both lung and liver. Analysis of the deoxyribonucleosides by high-pressure liquid chromatography showed that the major adduct in both tissues chromatographed as the (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI)-deoxyguanosine adduct. The (+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEII)-deoxyguanosine adduct was 9 to 15% of the BPDEI adduct in both lung and liver. Although total DNA-associated radioactivity was approximately 12-fold higher in liver than in lung, the specific activities of the BP diol-epoxide adducts were approximately the same in these organs. Treatment of animals with beta-naphthoflavone (beta NF), an inhibitor of pulmonary adenoma formation, markedly decreased the amount of the BDPEI and BPDEII adducts in the lung and the liver. The decrease in the amount of these adducts in the lung correlates with the inhibition of tumorigenesis by beta NF. The inhibition of total DNA-associated radioactivity was significantly less than the BP diol-epoxide adducts. Thus, beta NF appears to inhibit BP-induced pulmonary neoplasia by reducing the amount of the BPDEI-deoxyguanosine adduct. Other inducers of aryl hydrocarbon hydroxylase were also tested for their effect on the formation of BP-deoxyribonucleoside adducts. Both 2,3,7,8-tetrachlorodibenzo-p-dioxin and Aroclor 1254 significantly reduced the amount of the BPDEI adduct in both lung and liver. These data would suggest that both 2,3,7,8-tetrachlorodibenzo-p-dioxin and Aroclor 1254, like beta NF, should protect against BP-induced pulmonary neoplasia. The effects of aryl hydrocarbon hydroxylase inducers on the binding of BP to DNA in vivo markedly contrast with their effect in vitro. Treatment of animals with aryl hydrocarbon hydroxylase inducers stimulates the formation of BP diol-epoxide adducts in vitro. The reason for the differences between our in vivo results and those predicted from in vitro studies is unclear.

Influenza in China in 1977: recurrence of influenzavirus A subtype H1N1.

Preliminary results from epidemiological and laboratory studies on the new H1N1 influenza virus show that the 7-20 years age group suffered the highest morbidity; some adults over 20 years of age were also affected. The influenza epidemic caused by the H1N1 virus was characterized by slow spread, unevenness of attack rates, and the occurrence of many mild cases and inapparent infections. At least up to the end of 1977 there was concurrent persistence and spread of both H1N1 and H3N2 viruses. The H and N antigens of the new H1N1 virus, as well as its behaviour toward nonspecific inhibitors, were found to be closely similar to the old H1N1 virus prevalent during the first half of the 1950s. Most of the new H1N1 isolates in eggs were found to be temperature sensitive.