[Research advances on the application of natural and recombinant collagen in wound repair].

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

[Effect of platelet reactivity on clinical events in patients using bivalirudin in selective percutaneous coronary intervention].

Objective: To investigate the effect of platelet reactivity and other clinical factors on the postoperative 1-year adverse clinical events in patients who underwent selective percutaneous coronary intervention (PCI) anticoagulated with bivalirudin. Methods: This is a multicenter, retrospective and observational study, enrolling 632 patients at high risk of bleeding adjudicated by operators who underwent selective PCI anticoagulated with bivalirudin and had preoperative thrombelastography (TEG) test results in Fuwai Hospital, Northern Theater General Hospital and Xinxiang Central Hospital between January 2017 and August 2018. Platelet reactivity was tested by TEG and adenosine-induced maximal amplitude (MAADP) was recorded. According to MAADP patients were divided into three groups: low on-treatment platelet reactivity (LTPR) group (MAADP<31 mm, n=229), normal on-treatment platelet reactivity (NTPR) group (31 mm≤MAADP≤47 mm, n=207) and high on-treatment platelet reactivity (HTPR) group (MAADP>47 mm, n=196). The endpoints consisted of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events. The definition of MACCE was the composite of all-cause mortality, myocardial infarction, intrastent thrombosis, stroke and revascularization. Bleeding events were defined by bleeding academic research consortium (BARC) type 2, 3 and 5 bleeding. Using multivariate Cox regression to analyze the factors of MACCE and bleeding events in patients underwent selective PCI anticoagulated with bivalirudin. Results: A total of 632 patients were finally enrolled in the study with age of (68.3±10.0) years and there were 423 (66.9%) males. All of 632 patients finished one-year follow-up, and 48 (7.6%) patients occurred MACCE and 11 (1.7%) patients occurred bleeding events. There was not statistically significant difference in the incidence of MACCE (8.3% (19/229) vs. 6.3% (13/207) vs.8.2% (16/196), P=0.68) and bleeding events (1.8% (4/229) vs. 2.9% (6/207) vs. 0.5% (1/196), P=0.17) in LTPR, NTPR and HTPR group. Multivariate Cox regression showed that HTPR was not the independent factor of MACCE (HR=1.25, 95%CI 0.67-2.30, P=0.49), and the history of peripheral vessel disease was the independent risk factor of MACCE (HR=2.47, 95%CI 1.19-5.11, P=0.02). LTPR was not the independent factor of bleeding events (HR=1.35, 95%CI 0.39-4.66, P=0.64), and the independent factors of bleeding events were history of peripheral vessel disease (HR=3.95, 95%CI 1.03-15.22, P=0.05) and hemoglobin (HR=0.96, 95%CI 0.93-0.99, P=0.01). Conclusions: In patients undergoing selective PCI anticoagulated with bivalirudin, there is no significant association between platelet reactivity and postoperative 1-year MACCE or bleeding events. History of peripheral vessel disease is an independent risk factor of MACCE, and history of peripheral vessel disease and decreased hemoglobin are independent risk factors of bleeding events.

[The diagnostic performance of galactomannan detection in invasive pulmonary aspergillosis with severe and critically ill influenza].

Objective: To analyze the diagnostic performance of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) test in invasive pulmonary aspergillosis(IPA) with severe and critically ill influenza. Methods: A retrospective study was performed for 157 patients with severe and critically ill influenza admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to April 2019.Clinical characteristics and serum and BALF GM values were collected. The patients were divided into an IPA group (n=18) and a non-IPA group (n=139). The definition of IPA modified from AspICU algorithm taken as the gold standard (The corresponding clinical manifestations, imaging manifestations and microbiological diagnostic criteria should be met simultaneously), the performance of serum and BALF GM test and their combination to IPA with influenza were analyzed respectively and receiver operating characteristic curve (ROC) was drawn. Results: A total of 157 cases were enrolled, 95 were critically ill, and the mortality of IPA with influenza was 55.6%(10/18). The APACHE Ⅱ score, PSI score, urea nitrogen, influenza severity (Percentage of critically ill influenza) and invasive ventilator in IPA group were (16±6), (110±31), 10.7 (8.4, 17.8) mmol/L, 88.9% and 66.7%, respectively, which were significantly higher than those in non-IPA group [(10±5), (83±30), 5.2 (3.6, 7.6) mmol/L, 56.8% and 24.5%, P<0.05]. All patients received serum GM test and 32 patients performed BALF GM test at the same time. When the cut-off valve of serum GM test was 0.5 µg/L, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 66.7% (12/18), 95.0% (132/139), 63.2% (12/19) and 95.7% (132/138) respectively. When the cut-off value of BALF GM test was 1.0 µg/L, the sensitivity, specificity, PPV and NPV were 80%(8/10),86.4%(19/22),72.7%(8/11)and 90.5%(19/21)respectively. The BALF GM cut-off value of 0.88 µg/L showed the highest diagnostic efficacy for IPA, for which the sensitivity and specificity were 90%(9/10) and 86.4%(19/22). The areas under the ROC curve of serum GM, BALF GM, and the combination of them were 0.81, 0.85, and 0.94 respectively. The difference was statistically significant (P<0.05) and the combined diagnosis efficiency was higher. Conclusions: Critically ill influenza patients should be alert for IPA. The sensitivity of serum GM test in the diagnosis of IPA with influenza was low, while the NPV was high. The optimum BALF GM cut-off value was 0.88 µg/L. The combination with BALF and serum GM test can improve the diagnostic performance.

[Diagnostic performance of pathology, culture and ROSE of lung biopsy for suspected pulmonary infectious diseases].

Objective: To explore the diagnostic performance of CT guided percutaneous lung biopsy (PTLB) with pathology, culture and rapid on-site evaluation (ROSE) in patients with pulmonary infectious diseases. Methods: From January 2016 to June 2018, a retrospective study was implemented in the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University. Patients who received PTLB, suspected with lung infection were included. The basic information, clinical symptoms, imaging findings, diagnostic methods, complications, and changes in treatment of cases were collected. The diagnostic sensitivity of histopathology, microbial culture, and ROSE were evaluated at the same time. Results: A total of 529 cases were enrolled, including 354 males and 175 females, (59±14) years old in average. Tuberculosis was identified in 197 cases, non-tuberculosis mycobacteria (NTM) pulmonary disease in 8, cryptococcosis in 95, pulmonary aspergillosis in 27, filamentous fungal pneumonia in 3, talaromyces marneffei pulmonary infection in 3 and pulmonary candidiasis in 1, bacterial pneumonia in 39, and pathogen were unknown in 156 cases. A total of 417 cases were submitted for histopathology and microbial culture at the same time, the diagnostic value of pathology and microbial culture were 35.0% (146/417) and 45.6% (190/417), respectively. Combined pathology with microbial culture, the diagnostic value increased to 62.8% (262/417). The diagnostic accuracy of ROSE was 51.8% (71/137). The most common complication of PTLB was pneumothorax 26.1% (138/529). 56.1% (297/529) of the patients received targeted treatment after the diagnosis was confirmed, and 43.9% (232/529) maintained the original treatment. Conclusion: The pathology, microbial culture, and ROSE of PTLB have relative high diagnostic value for pulmonary infectious diseases.

[Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma].

Objective: To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods: In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results: Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%, 7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high, medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%, 5/7 and 6/11 in high, medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15, 2/4 and 3/6, respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions: The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.

[Diagnostic performance of T-SPOT.TB on peripheral blood in combination with adenosine deaminase on pleural fluid for the diagnosis of tuberculous pleurisy within different age group].

Objective: To evaluate the performance of T cell enzyme-linked immuno-spot assay (T-SPOT) on peripheral blood in combination with adenosine deaminase (ADA) on pleural fluid for diagnosis of tuberculous (TB) pleurisy within different age groups. Methods: The data of patients with pleural effusion from the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from April 2012 to November 2016 were retrospectively analyzed, and the diagnoses of these patients were histopathologically confirmed through medical thoracoscopy. The cases who had confirmed diagnosis, in the same time, received peripheral blood T-SPOT.TB were enrolled. The performance of peripheral blood T-SPOT.TB in combination with pleural fluid ADA on diagnosing TB pleurisy in the younger patients (16-59 years old) and elderly patients (≥60 years old) were analyzed respectively. The sensitivity, specificity and the receiver operating characteristic (ROC) curve were adopted for statistical analysis. Results: A total of 448 cases were finally enrolled, 341(76.1%) confirmed with TB pleurisy, 224 males, 117 females, (47±19) years old; and 107 (23.9%) classified as non-TB pleurisy, 65 males, 42 females, (61±14) years old. There were 285 cases who were classified as younger group, and the other 163 cases were classified as elderly group. The sensitivity and specificity of peripheral blood T-SPOT.TB were 85.4% (204/239) and 71.7% (33/46) in the younger patients, 76.5% (78/102) and 59.0% (36/61) respectively in the elderly patients. The sensitivity of peripheral blood T-SPOT.TB in the younger patients was significantly higher than that in the elderly patients (P=0.047). The sensitivity and specificity were 99.2% and 95.7% in combination with peripheral blood T-SPOT.TB and pleural fluid ADA respectively in the younger patients. The area under ROC curve (AUC) of T-SPOT.TB in the younger patients was 0.833, AUC of T-SPOT.TB combined with ADA was 0.911. The combination test of 2 tests had the sensitivity of 96.1% and the specificity of 90.2% respectively in the elderly patients. The AUC of T-SPOT.TB in the elderly patients was 0.747, AUC of T-SPOT.TB combined with ADA was 0.911. Conclusion: Peripheral blood T-SPOT.TB combined with pleural fluid ADA can improve the diagnostic performance for TB pleurisy with different ages, especially for elderly patients who can't tolerate pleural biopsy.

Cloning and characterization of a farnesyl pyrophosphate synthase from Matricaria recutita L. and its upregulation by methyl jasmonate.

Matricaria recutita (L.), commonly known as chamomile, is one of the most valuable medicinal plants because it synthesizes a large number of pharmacologically active secondary metabolites known as α-bisabolol and chamazulene. Although the plant has been well characterized in terms of chemical constituents of essential oil as well as pharmacological properties, little is known about the genes responsible for biosynthesis of these compounds. In this study, we report a new full-length cDNA encoding farnesyl diphosphate synthase (FPS), a key enzyme in the pathway of biosynthesis of isoprenoids, from M. recutita. The cDNA of MrFPS comprises 1032 bp and encodes 343 amino acid residues with a calculated molecular mass of 39.4 kDa. The amino acid sequence homology and phylogenetic analysis indicated that MrFPS belongs to the plant FPS super-family and is closely related to FPS from the Asteraceae family. Expression of the MrFPS gene in Escherichia coli yielded FPS activity. Using real-time quantitative PCR, the expression pattern of the MrFPS gene was analyzed in different tissues of M. recutita as well as in response to methyl jasmonate. The expression analysis demonstrated that MrFPS expression varies in different tissues (with maximal expression in flowers and stems) and was significantly elevated in response to methyl jasmonate. This study will certainly enhance our understanding of the role of MrFPS in the biosynthesis and regulation of valuable secondary metabolites in M. recutita at a molecular level.

Molecular cloning and characterization of the full-length Hsp90 gene from Matricaria recutita.

Heat shock protein 90 (Hsp90) is one of the most abundant and conserved chaperone proteins and plays important roles in plant growth and responses to environmental stimuli. However, little is known regarding the sequence and function of Hsp90s in Matricaria recutita. In the present study, we cloned the full-length cDNA sequence of the hsp90 gene from this species. Using rapid amplification of cDNA ends technologies with 2 degenerate primers that were designed based on the hsp90 gene sequence from other members of Asteraceae, we isolated and characterized an Hsp90 homolog gene from M. recutita (Mr-Hsp90). The full-length Mr-hsp90 cDNA sequence, containing 2097 base pairs, encodes a protein of 698 amino acids. Based on amino acid sequence identity, Mr-Hsp90 showed high similarity to other cloned Hsp90 proteins. The Mr-Hsp90 protein was closely clustered with the Lactuca sativa in a phylogenetic tree. These results indicate that the cloned sequence of Mr-Hsp90 is a member of the Hsp90 family, which is reported for the first time in M. recutita. Next, we conducted a salt stress experiment to determine the protein's function under salt stress conditions. Survival of chamomile seedlings subjected to heat-shock pretreatment was significantly increased compared with groups that had not undergone heat-shock pretreatment in a salt stress environment. This indicates that Mr-Hsp90 plays an important role in the salt resistance of chamomile seedlings.

PGC-1ß modulates the expression of genes involved in mitochondrial function and adipogenesis during preadipocyte differentiation.

This study determined the expression of genes involved in mitochondrial function and adipogenesis at mRNA and protein levels by transfecting rat differentiating preadipocytes with siRNA/Lipofectamine complex and pcDNA-PGC-1ß (peroxisome proliferator-activated receptor-γ coactivator-1ß)/Lipofectamine complex, respectively, to further elucidate the role of PGC-1ß in white preadipocyte differentiation. The results showed that the transfection of PGC-1ß siRNA inhibited the expressions of mitochondrial genes malate dehydrogenase, carnitine palmitoyltransferase 1, nuclear respiratory factor 1, ATP synthesis, adipocyte differentiation key transcription factor peroxisome proliferator-activated receptor-γ, sterol regulatory element binding protein 1c and fatty acid synthetase, whereas the triglyceride synthesis was retarded (p < 0.05). Furthermore, overexpression of PGC-1ß up-regulated the expressions of adipogenic and mitochondrial biosynthetic marker genes and promoted triglyceride accumulation during 3T3-L1 adipocyte differentiation. These observations suggest that PGC-1ß modulates the expression of mitochondrial function and adipogenesis-related genes and affects white preadipocyte differentiation.

Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population.

In this study, we assessed the efficacy of various lipid and lipoprotein measurements at baseline for predicting the risk for coronary heart disease (CHD) and determined the associated risk of CHD in subgroups stratified by different lipid and lipoprotein screening strategies to evaluate the adequacy of current total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort study, a Chinese population-based prospective cohort study that began in 1990. During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD (aged > or =35 years) developed CHD. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001). Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to those with low levels of both LDL cholesterol (< or =130 mg/dl) and total cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD than those with similar LDL cholesterol levels but low total cholesterol/HDL cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of 130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate that current guidelines for lipid management may misclassify subjects with high levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL cholesterol. Using the ratio of total to HDL cholesterol as the initial screening tool can obviate this discrepancy.

Increased levels of tissue plasminogen activator antigen and factor VIII activity in nonvalvular atrial fibrillation: relation to predictors of thromboembolism.

INTRODUCTION: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. METHODS AND RESULTS: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. CONCLUSION: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation.

A growth curve analysis of stress and adolescent drug use.

The purpose of this paper is to describe and examine one pathway by which adolescent drug use increases during early and mid-adolescence. It draws upon recent research on adolescent stress, drug use, and family processes to describe an important stage of the life course. A chief principle underlying the proposed pathway is that the cumulative effect of stressful life experiences over time can lead to a steeper escalation of drug use in adolescence. Furthermore, based on previous stress research, we propose that this effect may be moderated by factors such as sex, income, family attachment, self-esteem, and mastery. Using 4 years of panel data from the Family Health Study (n = 651 adolescents ages 11-14 during Year 1), we estimate a hierarchical growth curve model that examines the time-varying effects of stressful life events and peer relations on drug use. The results indicate that experiencing a high number of life events over time is related to a significant "growth" of drug use, even after controlling for "growth" due to age or peer relations. In addition, this relationship is moderated by family attachment; high levels of attachment serve to diminish this growth significantly.

Stressful life events and adolescent substance use and depression: conditional and gender differentiated effects.

Stressful life circumstances have myriad influences on human health and behavior. Early research focused on the variable distribution of stress and its effects by socioeconomic status, race, and gender. More recent research indicates that variation by age is also an important consideration. For example, adolescent reactions to stressful life events are often inconsistent with adult reactions to similar life situations and transitions. Moreover, since most studies assess only a single outcome--usually depression--they risk classification bias since analyses exclude other potential stress-related outcomes. This paper assesses the gender distinct effects of stressful life events on two outcomes among adolescents, substance use and depressive symptoms. The results of a second-order regression model indicate that life events affect female, but not male, depressive symptoms, especially when self-esteem is low or mastery is high. Furthermore, life events affect substance use when peer drug use is high, or when parental support is low, but this latter effect is limited to female adolescents.

Parental substance use disorder, mediating variables and adolescent drug use: a non-recursive model.

AIMS: To develop and test a non-recursive model that examines the effects of parental psychoactive substance use disorder (PSUD) on the reciprocal relationships among stressful life events, family attachment, peer drug use and adolescent drug use. DESIGN: A 3-year prospective cohort study followed adolescents from three types of families defined by a parental diagnosis of a psychiatric disorder. SETTING: A large metropolitan area in the upper Midwestern United States. PARTICIPANTS: Seven hundred and seventy-seven 10-16-year-old adolescents from three groups of families: 214 who resided in families in which a parent was diagnosed with PSUD, 181 who resided in families in which a parent was diagnosed with an affective disorder (but no co-morbid PSUD), and 382 who resided in families in which both parents were free of any diagnosable disorder. MEASUREMENTS: Psychiatric disorder was defined by the Structured Clinical Interview for DSM-III-R (SCID). Two follow-up interviews of adolescent respondents were used to measure stressful life events via the Junior High Life Experiences Survey, family attachment via FACES-III and a child-parent strain index, peer drug use, and two self-reported drug use scales designed to measure past-year alcohol use and illicit drug use (e.g. marijuana, cocaine, inhalants). FINDINGS: Nested structural equation models with latent variables revealed that adolescents from PSUD families were at heightened risk of stressful life events, peer drug use, attenuated family attachments and drug use during the first follow-up period. In turn, peer drug use was strongly associated with drug use during the second follow-up period. However, drug use during the first follow-up also led to greater peer drug use and attenuated family attachment during the second follow-up period. The findings support a non-recursive model describing relations among adolescent drug use, peer drug use and family attachment. CONCLUSIONS: Parental psychoactive substance use disorder puts adolescents at significant risk of becoming embedded in a cycle of drug use, associations with drug using peers, and poor family relations.

Effect of parental mental health status on adolescents' dietary behaviors.

PURPOSE: The purpose of this study was to explore whether adolescents of substance-abusing and depressed parents were more likely to have poor dietary behaviors than those in the health comparison families. METHODS: The sample consisted of 841 adolescents in families of substance-abusing parents, depressed parents, and parents without a diagnosable psychiatric disorder. All adolescents were given a food frequency questionnaire. RESULTS: Adolescents whose parents had substance abuse disorder had lower intakes of fruits and higher intakes of high fat foods, and also ate more frequently at fast-food restaurants and purchased more snacks. Adolescents whose parents were depressed had lower intakes of all food groups. Mother's mental health status impacted more on adolescents' dietary behaviors than did the father's mental health status. CONCLUSION: This research suggests that at-risk behaviors among youth of psychiatrically impaired parents may extend to food behaviors.

Changes in network characteristics and HIV risk behavior among injection drug users.

Studies indicate that HIV risk behaviors vary greatly among injection drug users (IDUs). The source of such variation is often ascribed to individual differences, but much of it is due to how IDUs are grouped into social networks. Nevertheless, given the turbulent and uncertain lives led by many IDUs, it would not be surprising if their social networks changed substantially over time. We used data from a study of the social networks of IDUs in Chicago and Washington, DC, to examine changes in individual behavior and network characteristics over time. The results indicated few changes in standard network measures, such as density of ties or network size, over time. However, specific network change measures, that is, indicators of movement into and out of networks, showed significant movement of network members over time. Moreover, movement of members into a network significantly predicted a higher likelihood of risky injection drug use over time. We suggest that these movements are indicative of a lack of a stable resource base among IDU networks.

A nitrogen starvation-induced dormant G0 state in fission yeast: the establishment from uncommitted G1 state and its delay for return to proliferation.

Fission yeast cells either remain in the mitotic cell cycle or exit to meiotic sporulation from an uncommitted G1 state dependent on the presence or absence of nitrogen source in the medium (Nurse and Bissett, 1981). We examined how heterothallic haploid cells, which cannot sporulate, behave under nitrogen-starvation for longer than 25 days at 26 degrees C. These cells were shown to enter a stable state (designated the dormant G0) with nearly full viability. Maintaining the dormant cells required glucose, suggesting that the cells remained metabolically active although cell division had ceased. They differed dramatically from mitotic and uncommitted G1 cells in heat resistance, and also in cytoplasmic and nuclear morphologies. After nitrogen replenishment, the initial responses of dormant G0 cells were investigated. The kinetics for reentry into the proliferative state were delayed considerably, and the changes in cell shape were enhanced particularly for those recovering from extended nitrogen starvation. A part of the delay could be accounted for by the duration of nuclear decondensation and cell elongation for the first cell division.

Molecular characterization of the yeast meiotic regulatory gene RIM1.

In the yeast Saccharomyces cerevisiae, genetic studies suggest that the RIM1 gene encodes a positive regulator of meiosis. rim1 mutations cause reduced expression of IME1, which is required for expression of many meiotic genes, and thus lead to a partial defect in meiosis and spore formation. We report the sequence of RIM1 and functional analysis of its coding region. The RIM1 gene product (RIM1) contains three regions similar to C2H2 zinc fingers. Serine substitutions for cysteine in each of the putative zinc fingers abolish RIM1 function. The carboxyl-terminus of RIM1 is enriched in acidic amino acids and is required for full RIM1 activity. RIM1 also contains two putative cAMP-dependent protein kinase (cAPK) phosphorylation sites. At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity. This analysis of RIM1 suggests that the protein may function as a transcriptional activator. We have used the cloned RIM1 gene to create a complete rim1 deletion. This null allele, like previously isolated rim1 mutations, causes a partial meiotic defect. In addition to RIM1, maximum IME1 expression requires the MCK1 and IME4 gene products. Defects associated with rim1, mck1, and ime4 mutations in expression of a meiotic reporter gene (ime2-lacZ) and in sporulation are additive. These findings suggest that RIM1 acts independently of MCK1 and IME4 to stimulate IME1 expression.

Identification of functionally related genes that stimulate early meiotic gene expression in yeast.

Meiosis and spore formation in the yeast Saccharomyces cerevisiae are associated with increased expression of sporulation-specific genes. One of these genes, IME2, encodes a putative protein kinase that is a positive regulator of other sporulation-specific genes. We have isolated mutations that cause reduced expression of an ime2-lacZ fusion gene. We found mutations in IME1, a known positive regultor of IME2, and MCK1, a known positive regulator of IME1. We also isolated recessive mutations in 12 other genes, which we designate RIM (Regulator of IME2) genes. Our analysis indicates that the defects in rim1, rim8, rim9 and rim13 mutants are a consequence of diminished IME1 expression and can be suppressed by expression of IME1 from the heterologous ACT1 promoter. These rim mutations also reduced expression of an ime1-HIS3 fusion, in which the HIS3 gene is expressed from the IME1 promoter, and caused reduced levels of IME1 RNA. Although the rim1, rim8, rim9 and rim13 mutant phenotypes are similar to those of mck1 mutants, we found that the defects in ime2-lacZ expression and sporulation of the mck1 rim double mutants were more severe than either single mutant. In contrast, the defects of the rim rim double mutants were similar to either single mutant. The rim1, rim8, rim9 and rim13 mutants also display slow growth at 17 degrees and share a smooth colony morphology that is not evident in mck1 mutants or isogenic wild-type strains. We suggest that RIM1, RIM8, RIM9 and RIM13 encode functionally related products that act in parallel to MCK1 to stimulate IME1 expression.