[The risk factors of first recurrence in ischemic stroke patients in different periods after first attack].

Objective: To investigate the risk factors of first recurrence in ischemic stroke patients at different periods after first attack. Methods: The subjects were from the screening population of China National Stroke Screening Survey (CNSSS) from 2013 to 2015. The basic demographic information, stroke history, influencing factors and modified Rankin Scale (mRs) scores were collected by using standardized face-to-face questionnaires. A case-control study was conducted to investigate the risk factors of first recurrence in ischemic stroke patients who relapsed for the first time within 12 months, 24 months and 36 months as the case group and non-recurrent ischemic stroke patients as the control group. Further, the subjects were stratified into different subgroups by age, gender and urban-rural distribution to investigate the risk factors of first recurrence in different periods. Results: Diabetes (OR=1.71, 95%CI: 1.08-2.71) and coronary heart disease (OR=1.55, 95%CI: 1.09-2.19) were significantly associated with the risk of first recurrence within 12 months after the first onset of ischemic stroke. The diabetes was significantly associated with the risk of first recurrence within 24 months (OR=1.94, 95%CI: 1.33-2.83) and 36 months (OR=1.64, 95%CI: 1.15-2.34) after the first onset of ischemic stroke. With the increase of mRs score, the risk of first recurrence within 12 months, 24 months and 36 months in ischemic stroke patients increased significantly. In the same period, the risk factors of ischemic stroke recurrence differed in patients with different age, gender and urban-rural distribution. Conclusions: The risk factors of first recurrence in ischemic stroke patients are diverse at different periods after the first onset of ischemic stroke. In different subgroups, the risk factors of first recurrence and the strength of its corresponding association are also different.

[On-site epidemiological investigation of a carbon monoxide poisoning incident].

Nighteen people at a restaurant experienced dizziness headaches and other discomforts in six days. According to the description method, the time and location distribution were found to be concentrated. A second Investigation was conducted at the same time as the onset of the case, the test found that the carbon monoxide concentration of second floor up to 539 mg/m(3). The on-site testing found that when 2 steam generator in snack room on the first floor turned on, the carbon monoxide concentration on the top of elevator on the second floor was 1225.0 mg/m(3). After the accident, the restaurant replaced a steam generator, the carbon monoxide concentration on the top of the new and old steam generator were 350 mg/m(3) and >1 000 mg/m(3), respectively. After the steam generators were fitted with exhaust smoke pipe and exhasust hood, the carbon monoxide concentrations of on the top of the vegetable transfer elevator and the room on the second floor were both 0.4 mg/m(3), and there were no cases of recurrence. It was determined that this was a carbon monoxide poisoning incident caused by a high concentration of carbon monoxide emitted by the steam generators, which spread to the second floor of the private room through the vegetable transfer elevator.

[The epidemiological characteristics and adherence to hypoglycemic agents of ischemic stroke patients with diabetes].

Objective: To investigate the epidemiological characteristics and adherence to hypoglycemic agents of the ischemic stroke patients combined with diabetes. Methods: The study recruited 23 044 ischemic stroke cases from 2013-2015 screening period of China National Stroke Screening Survey. Standardized questionnaires were used to obtain information on demographic data, stroke history, the presence of influence factors, as well as the type of stroke, diagnosis date, frequency, chronic diseases history and hypoglycemic therapy. We used logistics model to investigate the possible risk factors of ischemic stroke combined with diabetes, and calculated the population attributable risk proportion (PARP). We also investigate the adherence to hypoglycemic agents. Results: The mean age of 23 044 ischemic stroke patients was (64.99±9.42) years old, 50.91% were males (11 731). In ischemic stroke patients, 21.52% had diabetes. According to the results of logistics model, ischemic stroke patients with hypertension, dyslipidemia, atrial fibrillation or family history of stroke had higher risk to combine with diabetes, their Odds Ratios (OR) were 2.18 (1.87-2.55), 1.99 (1.78-2.23), 1.64 (1.39-1.92) and 1.19 (1.06-1.33). Considering the prevalence of each influence factor in ischemic stroke patients, atrial fibrillation had the highest PARP (95%CI) of 62.65% (61.27%-63.76%). In ischemic stroke patients combined with diabetes, 70.73% (3 463/4 896) had taken hypoglycemic agents. Conclusion: There still were a large number of ischemic stroke patients combined with diabetes and a low rate of adherence to hypoglycemic agents.

[Gender-specific factors of ischemic stroke among atrial fibrillation patients].

Objective: To explore gender-specific factors and their contributions to ischemic stroke among atrial fibrillation (AF) patients. Methods: A case-control study was conducted. The relevant data were obtained from the database of China National Stroke Screening Survey. The cases were first-ever ischemic stroke cases diagnosed from September 2013 to September 2015. Frequency-matched for the age and distribution of city and country, controls were randomly selected by 1∶3 ratio from individuals with AF but without stroke in the program. Altogether, there were 85 male cases (320 controls) and 147 female cases (484 controls). Unconditional logistic regression model was applied for the analysis of relevant factors of the onset of ischemic stroke, and their population-attributable risk proportion [PARP, (95%CI)] was calculated. Results: The age of male subjects in the case group and control group were (65.26±11.20) and (64.83±11.08) years old, and that of females in two groups were (63.63±10.40) and (63.93±10.35) years old. According to the PARP (95%CI), relevant factors of the onset of ischemic stroke in a descending sequence were hypertension history [35.63 (18.64-47.73)], family history of stroke [28.70 (23.63-32.30)]and physical inactivity [15.73 [5.62-23.06)] among male AF patients, and family history of stroke (29.39 (24.21-33.08)), dyslipidemia (22.17 (2.26-36.45)) and smoking [2.09 (0.76-3.24)] among female AF patients. Conclusion: The relevant factors of ischemic stroke were different between male and female AF patients.

[The association of health-related behavior and the risk of stroke in people with hypertension].

Objective: To investigate the association between the combination of different health-related behaviors and the risk of stroke in people with hypertension. Methods: The data in this study were obtained from the China National Stroke Screening Survey (CNSSS). The case group was the people with hypertension who were also diagnosed as the first-ever stroke cases (total stroke and ischemic stroke) during 2013-2014 screening period. Their corresponding controls (1∶3 frequency-matched for age group and urban/rural ratio) were randomly selected from individuals with hypertension without stroke. The information on demographic data, stroke history, influence factors and health-related behaviors (non-smoking, normal body mass index maintenance and physical activity) was obtained using standardized face-to-face questionnaires. Univariate analysis included t-test and Chi-square test. Multivariate analysis included unconditional logistic regression. Results: There were 603 total stroke cases (1 909 controls) and 536 ischemic stroke cases (1 608 controls) in men with hypertension, and 600 total stroke cases (1 800 controls) and 534 ischemic stroke cases (1 602 controls) in women with hypertension. We found that women with three health-related behaviors had lower risk of total stroke (OR=0.29, 95%CI: 0.11-0.79) and ischemic stroke (OR=0.28, 95%CI: 0.10-0.77). Only the combination of non-smoking and physical activity was significantly associated with the decreased risk of total stroke (OR=0.30, 95%CI: 0.11-0.78) and ischemic stroke (OR=0.32, 95%CI: 0.12-0.87). We had not found significant association between the combination of different health-related behaviors and risk of total stroke and ischemic stroke (P>0.05) in men. Conclusion: This study indicated that health-related behavior intervention might be more effectively to prevent stroke in women with hypertension, especially the smoking control and physical activity.

Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene.

UNLABELLED: ESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will aid in studying FVIII inhibitor formation. BACKGROUND: The most important complication in hemophilia A treatment is the development of inhibitory anti-Factor VIII (FVIII) antibodies in patients after FVIII therapy. Patients with severe hemophilia who express no endogenous FVIII (i.e. cross-reacting material, CRM) have the greatest incidence of inhibitor formation. However, current mouse models of severe hemophilia A produce low levels of truncated FVIII. The lack of a corresponding mouse model hampers the study of inhibitor formation in the complete absence of FVIII protein. OBJECTIVES: We aimed to generate and characterize a novel mouse model of severe hemophilia A (designated the F8(TKO) strain) lacking the complete coding sequence of F8 and any FVIII CRM. METHODS: Mice were created on a C57BL/6 background using Cre-Lox recombination and characterized using in vivo bleeding assays, measurement of FVIII activity by coagulation and chromogenic assays, and anti-FVIII antibody production using ELISA. RESULTS: All F8 exonic coding regions were deleted from the genome and no F8 mRNA was detected in F8(TKO) mice. The bleeding phenotype of F8(TKO) mice was comparable to E16 mice by measurements of factor activity and tail snip assay. Similar levels of anti-FVIII antibody titers after recombinant FVIII injections were observed between F8(TKO) and E16 mice. CONCLUSIONS: We describe a new C57BL/6 mouse model for severe hemophilia A patients lacking CRM. These mice can be directly bred to the many C57BL/6 strains of genetically engineered mice, which is valuable for studying the impact of a wide variety of genes on FVIII inhibitor formation on a defined genetic background.

Impact of artificial reservoir water impoundment on global sea level.

By reconstructing the history of water impoundment in the world's artificial reservoirs, we show that a total of approximately 10,800 cubic kilometers of water has been impounded on land to date, reducing the magnitude of global sea level (GSL) rise by -30.0 millimeters, at an average rate of -0.55 millimeters per year during the past half century. This demands a considerably larger contribution to GSL rise from other (natural and anthropogenic) causes than otherwise required. The reconstructed GSL history, accounting for the impact of reservoirs by adding back the impounded water volume, shows an essentially constant rate of rise at +2.46 millimeters per year over at least the past 80 years. This value is contrary to the conventional view of apparently variable GSL rise, which is based on face values of observation.

Intramolecular Mannich reaction in the asymmetric synthesis of polysubstituted piperidines: concise synthesis of the dendrobate alkaloid (+)-241D and its C-4 epimer.

[reaction: see text] The intramolecular Mannich reaction of delta-amino beta-keto esters with aldehydes and ketones is a new methodology for the synthesis of polysubstituted piperidines and is illustrated by the concise asymmetric synthesis of the dendrobate alkaloid (+)-241D and its C-4 epimer.

Alkaloid synthesis using chiral delta-amino beta-ketoesters: a stereoselective synthesis of (-)-lasubine II.

[reaction: see text]A highly stereoselective asymmetric synthesis of the quinolizidinealkaloid (-)-lasubine II from a delta-amino beta-hydroxy ketone, a new polyfunctionalized chiral building block, is described.

Correlates of outpatient drug treatment drop-out among methamphetamine users.

This article explores correlates of retention among the 2.337 methamphetamine (MA) users entering public outpatient treatment programs in California from January 1, 1994 through September 30, 1997. A secondary analysis of data from the California Alcohol and Drug Data System (CADDS) was performed and predictors of drop-out before treatment completion (as measured by a retention of 180 days or more) were determined using logistic regression. Overall, 23.3% of MA users completed treatment, a rate similar to that for users of other drugs throughout California. As expected, MA users who were older (40 years or over), had less severe drug use patterns (used less than daily or did not inject), or who were under coerced treatment were significantly more likely to complete treatment that other MA users. Surprisingly, men were significantly more likely than women to drop out of treatment before 180 days. Until studies currently collecting primary data on MA treatment are completed, the present secondary analysis provides a useful foundation upon which future research and intervention strategies may be based.

delta-Amino beta-keto esters, a designed polyfunctionalized chiral building block for alkaloid synthesis. Asymmetric synthesis of (R)-(+)-2-phenylpiperidine and (-)-SS20846A.

[formula: see text] delta-Amino beta-keto esters 3 and 11 are designed polyfunctionalized chiral building blocks for alkaloid synthesis and are prepared in one step from the corresponding sulfinimine (N-sulfinyl imine). Concise highly enantioselective four-step syntheses of 2-phenylpiperidine (7) and SS20846A (14) from 3 and 11, respectively, are described.

ELISA methods for the analysis of antibody responses induced in multiple sclerosis patients treated with recombinant interferon-beta.

Upon treatment with protein therapeutics, a subset of patients will typically develop antibodies against the drug. These anti-drug antibodies can be of concern because they have the potential to alter the drug's therapeutic activity. In the case of relapsing-remitting multiple sclerosis (RRMS) patients receiving recombinant interferon-beta (IFN-beta), those receiving BETASERON (IFN-beta-1b; E. coli expressed, non-glycosylated, des-Met-1, Cys17Ser recombinant IFN-beta) have a higher incidence of IFN-beta specific antibodies compared to those receiving AVONEX (IFN-beta-1a; mammalian cell-expressed, natural sequence, glycosylated recombinant IFN-beta). The current study reports the development and characterization of ELISAs that detect distinct components of the anti-IFN-beta response in patients' sera, and therefore can potentially be used to characterize the composition of the anti-IFN-beta antibody response. ELISAs were developed using a constant detecting reagent but a variety of IFN-beta-derived test antigens (e.g., native IFN-beta, biotinylated IFN-beta, IFN-beta peptides) and capture methods. Assays were characterized using serum samples from a small number of patients treated with recombinant IFN-beta (either BETASERON or AVONEX). Assays in which IFN-beta was captured via a specific mAb, or in which biotinylated IFN-beta was captured via streptavidin, detected serum antibodies that recognize IFN-beta in its native structural state. In contrast, assays in which IFN-beta was coated directly onto the assay plates detected antibodies that recognize forms of IFN-beta possessing a folded structure distinct from the native structure. Certain epitopes present on native IFN-beta were not represented in these assays in which the test antigen was directly coated on plastic. Antibodies specific for linear epitopes could be detected using linear peptides as test antigens; the locations of these epitopes were mapped by reference to the X-ray crystal structure of IFN-beta-1a. Together, these data show that the mode of antigen presentation employed in IFN-beta ELISAs determines which antibody specificities are detected, and can affect whether or not a given serum sample is identified as positive for anti-IFN-beta antibodies. As a consequence, screening samples in a single ELISA format presenting IFN-beta in a non-native form may lead to underestimation of the incidence of IFN-beta treated MS patients that have generated antibodies specific to the native, active form of the drug.

Substance use and its relationship to depression, anxiety, and isolation among youth living with HIV.

Reductions from lifetime to recent levels of substance use, the time since HIV diagnosis, physical health symptoms, CD4 counts, emotional distress, and social supports were examined among 227 (20% female; 22% African American, 27% Anglo, 35% Latino) youth living with HIV (YLH) ages 13 to 24 years. Substance use pervaded the lives of these youth. Male YLH had used more drugs., more often, and for longer periods than women. However, there had been major reductions in use. Being male, having high emotional distress, and having fewer negative social supports were significantly associated with greater reductions in substance use. There was a trend for the length of time that an individual was seropositive being associated with reductions in substance use. The counterintuitive findings suggest that there must be a re-examination of the role of the social support networks of youth living with HIV, as well as the ways in which emotional distress interacts with risk behaviors.

Fibronectin type III repeats mediate RGD-independent adhesion and signaling through activated beta1 integrins.

Many cell-surface and extracellular matrix proteins contain multiple modular domains known as fibronectin type III (FNIII) repeats. Cells adhere to the extracellular matrix proteins fibronectin and tenascin in part by the interaction of certain integrins with the Arg-Gly-Asp (RGD) sequence, displayed on specific FNIII repeats. We have found that, after experimental activation of beta1 integrins, a number of cell types adhere and spread on FNIII repeats lacking RGD, derived from extracellular matrix proteins and cytokine receptors. Interaction between individual FNIII domains and beta1 integrins mediates focal adhesion kinase phosphorylation and subsequent stress fiber and focal contact formation. These data suggest that many FNIII-containing proteins may bind and signal through activated beta1 integrins, dramatically expanding the potential for integrin-dependent intercellular and cell-matrix communication.

The Structure of W/C (0.15 < γ < 0.8) Multilayers Annealed in Argon or Air.

We report the effect that thermal annealing in inert and oxidizing atmospheres, and with and without encapsulating layers, has on the structure of tungsten/carbon [W/C] multilayer thin films. This study focuses on the tungsten component and deals mainly with multilayers where the ratio of thickness of tungsten layers is equal to or greater than for the carbon layers (that is, γ ≤ 0.5). This is in contrast to prior studies where the tungsten layer thickness was generally held constant and the carbon layer was varied. Thermal annealing in inert atmospheres produces reactions and other structural changes in the tungsten and carbide layers which depend on the as-deposited multilayer structure which depends, in turn, on the thickness of the tungsten layer. In samples where both the tungsten and carbide fractions of the multilayer are completely amorphous as deposited, which is the case for thin tungsten layers (thickness of tungsten (tw) < 4 nm/period), the reactions in the tungsten layer forming crystalline tungsten and tungsten carbide occur at annealing temperatures above 900°C. The layer pair spacing, or period, (d), in this group shows an expansion of up to 10-15% of the original value as has been reported in the past. Changes in both the tungsten and carbide layers, and their interfaces, contribute to changes in d spacing and relative thickness of the high and low Z components. When the tungsten layer thickness exceeds 4 nm per period the tungsten is partially crystallized in as-prepared samples. In such multilayers interfacial reactions, producing an oriented partially crystalline W2C/C superlattice, occur at temperatures of 600°C and below. The fact that W2C crystallites in one period can form a structure which is correlated to W2C crystallites in neighboring layers is somewhat surprising, since layers are presumably still separated by amorphous carbon which is still visible via Raman. The expansion of the layer pair spacing is relatively small (<5%) in this group and, more importantly, mostly involves increases in the thickness of the high Z components. Samples annealed in air at temperatures below 300°C are progressively destroyed by the oxidation of both tungsten and carbide layers. Encapsulation of similar multilayers with a thin (30 nm) dielectric layer of any of several types can retard oxidation to 600°C. The silicon-containing encapsulants generally perform better. Failure at this temperature is seen to occur from pinhole formation.

Sexual abuse during childhood and adolescence as predictors of HIV-related sexual risk during adulthood among female sexual partners of injection drug users.

PIP: This study explores the relationship of sexual abuse during childhood and adolescence with HIV-related sexual risk behaviors during adulthood among female sexual partners of injection drug users. It analyzed data that was gathered between 1990 and 1993, which included a sample of 2794 women from the US, Mexico, and Puerto Rico. 6 HIV-related sexual risk behaviors that occurred during the month prior to interview were examined; namely, number of sexual partners, number of drug-injecting sexual partners, number of sexual intercourse while high on alcohol and/or other drugs, number of times trading sex for drugs and/or money, proportion of all sexual acts involving protection, and overall HIV-related sexual risk. The results showed that more than one-third of the women (36.3%) experienced some form of sexual abuse during childhood, whereas 34.4% reported that they had been abused sexually during adolescence; 1 in 5 women (18.4%) stated being abused during both periods. The results further indicate that there is a strong link between sexual abuse victimization early in life and involvement later in life in HIV-related sexual risk behaviors. It was found out that certain forms of sexual abuse, such as forced exposure and touching of one's sexual parts were more strongly related than other forms of sexual abuse to subsequent involvement in HIV-related sexual behaviors.^ieng

Diurnal and Semidiurnal Variations in the Earth's Rotation Rate Induced by Oceanic Tides.

Recent space-geodetic observations have revealed daily and subdaily variations in the Earth's rotation rate. Although spectral analysis suggests that the variations are primarily of tidal origin, comparisons to previous theoretical predictions based on various ocean models have been less than satisfactory. This disagreement is partly caused by deficiencies in physical modeling. Rotation predictions based on a reliable tidal-height model, with corresponding tidal currents inferred from a modified form of Laplace's momentum equations, yield predictions of tidal variations in Universal Time that agree with very long baseline interferometer observations to 2 microseconds. This agreement resolves a major discrepancy between theory and observation and establishes the dominant role of oceanic tides for inducing variation in the Earth's rotation at these frequencies.

Essential groups in synthetic agonist peptides for activation of the platelet thrombin receptor.

Thrombin appears to activate platelets by a novel mechanism that involves the cleavage of its receptor, and it has been proposed that the newly generated N-terminal region of the receptor then acts as a tethered ligand [Vu, T. H., Hung, D. T., Wheaton, V. I., & Coughlin, S. R. (1991) Cell 64, 1057-1068]. Peptides with sequences corresponding to those of the tethered ligand are capable of activating the receptor. In the present study, groups within this tethered ligand peptide that are important for activation of the receptor have been identified by synthesizing a series of peptides. A 14-residue peptide based on the tethered ligand stimulated the aggregation of gel-filtered platelets with an EC50 of 7 microM, and a concentration of 10 microM was the minimum concentration necessary to yield a full aggregation response in platelet-rich plasma. Truncation of the peptide from the C-terminus to nine residues did not markedly affect the response to the peptide. Shorter peptides of five, six, and eight amino acids retained their agonist activity, but the minimal concentration necessary to achieve a full aggregation response in platelet-rich plasma was 2-5-fold higher. Side chains within the tethered ligand peptide that are important for receptor activation were identified by synthesizing a series of peptides in which residues were sequentially replaced by alanine. The results indicated that the side chains of phenylalanine, leucine, and arginine in positions 2, 4, and 5, respectively, are essential for full activity. Most notably, substitution of phenylalanine in the second position resulted in complete loss of agonist activity at concentrations up to 800 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure-function relationships of hirulog peptide interactions with thrombin.

Using hirudin as a model, a novel class of bivalent thrombin inhibitors has been designed and characterized (Maraganore et al. (1990) Biochemistry 29, 7095-7101). These peptides, designated 'hirulogs', interact with both thrombin's catalytic center and its anion-binding exosite for fibrinogen recognition. In order to investigate structure-activity relationships in hirulog peptides, a number of peptide and peptidomimetic derivatives with alterations in catalytic-site binding and anion-binding exosite binding moieties were prepared. Replacements or modifications in the catalytic site and exosite binding moieties were achieved with the consequences of maintaining or improving antithrombin activity. In addition to showing improved affinity for thrombin, some derivatives with Ki's in the sub-nanomolar range showed increased anticoagulant activities. These findings highlight the versatility of hirulog peptides in their bivalent interactions with thrombin.