Differentiated health problems according to gender among adolescents reporting sexual or physical assault

Background and objectives: Gender studies previously enlightened our research. Gender differences among traumatized adolescents remain understudied. We hypothesized that comparing health problems between adolescents reporting physical assault and adolescents reporting sexual assault could show a gender difference and could help to identify risks.MethodsIn our 1993 cross-sectional epidemiological representative survey of adolescents in France – 14 278 enrolled in the school system, and 3005 who had left school – we selected the 5893 adolescents in the 16–20 age span, and extracted the sub-sample of 1324 who reported sexual or physical assaults (23%). The symptoms noted were not necessarily a consequence of the assault, but they clearly captured health states in these groups.ResultsThe rate of sexual assault reports by adolescents who left the school system (9.4%) was higher than in the other group (4.2%, p < 0.001). The symptoms selected for the comparisons sexual / physical were chosen because they were significantly more frequent (p < 0.001) among adolescents reporting assault compared to non-assaulted adolescents. For each gender and each type of assault, these symptoms were explored using logistic regressions, adjusting age and schooling status (being inside or outside the school system): among boys, health problems seem more salient when the assault report was sexual rather than physical (e.g. suicide attempts: OR = 3.9, 95%CI = [1.9–8.0]); in contrast, among girls, the two groups seem equally affected.ConclusionThis gender study highlights the risk of suicide among assaulted adolescents. Sexually assaulted boys require care, including suicide prevention, even though they seem to cope effectively with physical assault. (AU)

Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity.

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.

Prevalence of endocrine disorders in obese patients: systematic review and meta-analysis.

OBJECTIVE: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. DESIGN: Systematic review and meta-analysis of the literature. METHODS: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). RESULTS: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. CONCLUSIONS: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45-/CD34+/CD31- progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1-/CD271- and MSCA1-/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFß-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks.

Impact of Intragastric Balloon Before Laparoscopic Gastric Bypass on Patients with Super Obesity: a Randomized Multicenter Study.

BACKGROUND: Super obese patients are recommended to lose weight before bariatric surgery. The effect of intragastric balloon (IGB)-induced weight loss before laparoscopic gastric bypass (LGBP) has not been reported. The aim of this prospective randomized multicenter study was to compare the impact of preoperative 6-month IGB with standard medical care (SMC) in LGBP patients. METHODS: Patients with BMI >45 kg/m2 selected for LGBP were included and randomized to receive either SMC or IGB. After 6 months (M6), the IGB was removed and LGBP was performed in both groups. Postoperative follow-up period was 6 months (M12). The primary endpoint was the proportion of patients requiring ICU stay >24 h; secondary criteria were weight changes, operative time, hospitalization stay, and perioperative complications. RESULTS: Only 115 patients were included (BMI 54.3 ± 8.7 kg/m2), of which 55 underwent IGB insertion. The proportion of patients who stayed in ICU >24 h was similar in both groups (P = 0.87). At M6, weight loss was significantly greater in the IGB group than in the SMC group (P < 0.0001). Three severe complications occurred during IGB removal. Mean operative time for LGBP was similar in both groups (P = 0.49). Five patients had 1 or more surgical complications, all in the IGB group (P = 0.02). Both groups had similar hospitalization stay (P = 0.59) and weight loss at M12 (P = 0.31). CONCLUSION: IGB insertion before LGBP induced weight loss but did not improve the perioperative outcomes or affect postoperative weight loss.

Poor prognosis of pregnancy in women with autoimmune type 1 diabetes mellitus masquerading as gestational diabetes.

AIM: To describe the clinical presentation and the prognosis of autoimmune type 1 diabetes (T1D) that was first revealed during pregnancy masquerading as gestational diabetes mellitus (GDM). METHODS: We reviewed the files of 21 women in whom diabetes was revealed during a pregnancy ("index pregnancy") and progressed to T1D after delivery, and in whom GAD and/or IA-2 autoantibodies were found. RESULTS: The median age and BMI of the women were 31 years and 19.8 kg/m(2). Eleven women had at least one risk factor for GDM. Eight of the 12 multiparous women had had an abnormal outcome of previous pregnancy, including GDM in five. GDM was diagnosed at week 26 (range: 4-38) of gestation by screening in 18, because of macrosomia in two and during hyperglycaemic crises in three. All were treated with insulin, from the time of diabetes diagnosis in 10 and after 4 weeks (range: 2-15) in 11. Term of delivery was 38 (range: 26-41) weeks. Abnormal outcomes occured in 14 pregnancies, including two fetal deaths, four preterm deliveries and eight macrosomic infants. No congenital malformations were reported. After delivery, insulin therapy was stopped in 18 women for 6 months (range: 2-48). The diagnosis of the autoimmune origin of diabetes was established during the index pregnancy in only eight cases. CONCLUSION: T1D may reveal as GDM in women with or without risk factors for GDM and is associated with a poor prognosis, partly because the correct diagnosis and treatment are delayed. Whether screening for autoimmune markers of T1D should be performed more systematically in women with GDM deserves to be studied.

Mechanical sludge disintegration: providing an alternative carbon source for nutrient removal.

The primary driver for efficient biological nutrient removal (BNR) in activated sludge treatment is the sufficient supply of soluble carbon. Several methods have been proposed to increase available carbon sources and enhance BNR. This study examines the effect of ultrasonic equipment and mechanical disintegration technologies on surplus activated sludge (SAS), to release additional soluble chemical oxygen demand (SCOD) and volatile fattty acids (VFA), as a carbon food source for BNR. A laboratory sonicator with a maximum power of 550W, a 3KW SONIX radial horn and a deflaker declared to be used in the paper industry were investigated. All caused significant release of SCOD, up to 48 fold. The maximum concentration of VFA reached (from 0-1 mg 1(-1)), was 530 mg 1(-1). To assess the likely impact to BNR, batch (21) anaerobic lab tests examining the use of disintegrated sludge on phosphorus and nitrogen removal were completed. Phosphorus removal was estimated by observing the phosphate release under anaerobic conditions and up to 460% more release was observed relative to controls. In addition, denitrification rates were improved by over 106%. Ultrasonic and mechanical disintegration technologies have been shown to release soluble carbon for BNR, with subsequent laboratory nitrogen and phosphorus removal efficiencies observed to be comparable to acetate.

Mechanical sludge disintegration for the production of carbon source for biological nutrient removal.

The primary driver for a successful biological nutrient removal is the availability of suitable carbon source, mainly in the form of volatile fatty acids (VFA). Several methods have been examined to increase the amount of VFAs in wastewater. This study investigates the mechanism of mechanical disintegration of thickened surplus activated sludge by a deflaker technology for the production of organic matter. This equipment was able to increase the soluble carbon in terms of VFA and soluble chemical oxygen demand (SCOD) with the maximum concentration to be around 850 and 6530 mgl(-1), for VFA and SCOD, respectively. The particle size was reduced from 65.5 to 9.3 microm after 15 min of disintegration with the simultaneous release of proteins (1550 mgl(-1)) and carbohydrates (307 mgl(-1)) indicating floc disruption and breakage. High performance size exclusion chromatography investigated the disintegrated sludge and confirmed that the deflaker was able to destroy the flocs releasing polymeric substances that are typically found outside of cells. When long disintegration times were applied (>or=10 min or >or=9000 kJkg(-1)TS of specific energy) smaller molecular size materials were released to the liquid phase, which are considered to be found inside the cells indicating cell lysis.

Palmitate induced mitochondrial deoxyribonucleic acid damage and apoptosis in l6 rat skeletal muscle cells.

A major characteristic of type 2 diabetes mellitus (T2DM) is insulin resistance in skeletal muscle. A growing body of evidence indicates that oxidative stress that results from increased production of reactive oxygen species and/or reactive nitrogen species leads to insulin resistance, tissue damage, and other complications observed in T2DM. It has been suggested that muscular free fatty acid accumulation might be responsible for the mitochondrial dysfunction and insulin resistance seen in T2DM, although the mechanisms by which increased levels of free fatty acid lead to insulin resistance are not well understood. To help resolve this situation, we report that saturated fatty acid palmitate stimulated the expression of inducible nitric oxide (NO) synthase and the production of reactive oxygen species and NO in L6 myotubes. Additionally, palmitate caused a significant dose-dependent increase in mitochondrial DNA (mtDNA) damage and a subsequent decrease in L6 myotube viability and ATP levels at concentrations as low as 0.5 mM. Furthermore, palmitate induced apoptosis, which was detected by DNA fragmentation, caspase-3 cleavage, and cytochrome c release. N-acetyl cysteine, a precursor compound for glutathione formation, aminoguanidine, an inducible NO synthase inhibitor, and 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (III), a peroxynitrite inhibitor, all prevented palmitate-induced mtDNA damage and diminished palmitate-induced cytotoxicity. We conclude that exposure of L6 myotubes to palmitate induced mtDNA damage and triggered mitochondrial dysfunction, which caused apoptosis. Additionally, our findings indicate that palmitate-induced mtDNA damage and cytotoxicity in skeletal muscle cells were caused by overproduction of peroxynitrite.

Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults.

Cells of the CNS are constantly exposed to agents which damage DNA. Although much attention has been paid to the effects of this damage on nuclear DNA, the nucleus is not the only organelle containing DNA. Within each cell, there are hundreds to thousands of mitochondria. Within each mitochondrion are multiple copies of the mitochondrial genome. These genomes are extremely vulnerable to insult and mutations in mitochondrial DNA (mtDNA) have been linked to several neurodegenerative diseases, as well as the normal process of aging. The principal mechanism utilized by cells to avoid DNA mutations is DNA repair. Multiple pathways of DNA repair have been elucidated for nuclear DNA. However, it appears that only base excision repair is functioning in mitochondria. This repair pathway is responsible for the removal of most endogenous damage including alkylation damage, depurination reactions and oxidative damage. Within the rat CNS, there are cell-specific differences mtDNA repair. Astrocytes exhibit efficient repair, whereas, other glial cell types and neuronal cells exhibit a reduced ability to remove lesions from mtDNA. Additionally, a correlation was observed between those cells with reduced mtDNA repair and an increase in the induction of apoptosis. To demonstrate a causative relationship, a strategy of targeting DNA repair proteins to mitochondria to enhance mtDNA repair capacity was employed. Enhancement of mtDNA repair in oligodendrocytes provided protection from reactive oxygen species- and cytokine-induced apoptosis. These experiments provide a novel strategy for protecting sensitive CNS cells from genotoxic insults and thus provide new treatment options for neurodegenerative diseases.

Expression of adiponectin and its receptors in swine.

Adiponectin is an adipocyte-derived hormone that plays an important role in lipid metabolism and glucose homeostasis. Objectives of this study were 1) to determine the presence and distribution of adiponectin and its receptors 1 and 2 (adipoR1 and adipoR2) in porcine tissues; 2) to characterize pig adiponectin, adipoR1, and adipoR2 mRNA levels in various fat depots from three different breeds of pigs; and 3) to study, in stromal-vascular cell culture, the effects of leptin and tumor necrosis factor-alpha (TNFalpha) on pig adiponectin, adipoR1, and adipoR2 gene expression. To this end, fat Chinese Upton Meishan (UM, n = 10), lean Ham Line (HL, n = 10), and Large White (LW, n = 10) gilts were used. We report the isolation of partial cDNA sequences of pig adipoR1 and adipoR2. Porcine-deduced AA sequences share 97 to 100% homology with human and murine sequences. Pig adipoR1 mRNA is abundant in skeletal muscle, visceral fat, and s.c. fat tissues, whereas adipoR2 mRNA is predominantly expressed in liver, heart, skeletal muscle, and visceral and s.c. fat tissues. Pig adiponectin mRNA levels in s.c. and visceral fat tissues were not associated with plasma insulin and glucose in fasting animals. Subcutaneous (r = -0.44, P < 0.05), visceral (r = -0.43, P < 0.05), and total body fat (r = -0.42, P < 0.05) weights were negatively correlated with adiponectin mRNA levels measured in visceral, but not s.c., fat. Pig adipoR1 and adipoR2 mRNA levels, in visceral fat, were less expressed in fat UM gilts than in the lean HL gilts (P < 0.05). Inverse associations were found between s.c. (r = -0.57, P < 0.01), visceral (r = -0.46, P < 0.05), and total body fat (r = -0.56, P < 0.01) weights and adipoR2 mRNA levels in visceral fat only. We were unable to find such associations for adipoR1 mRNA levels in the overall gilt population. The current study demonstrated that TNFalpha downregulates adiponectin and adipoR2, but not adi-poR1, mRNA levels in stromal-vascular cell culture. Moreover, leptin significantly decreased adiponectin mRNA levels, whereas there was no effect on adiponectin receptors. We conclude that adiponectin and adi-poR2 mRNA levels, but not adipoR1, are modulated in pig visceral fat tissues. Furthermore, our results indicate that TNFalpha interferes with adiponectin function by downregulation of adipoR2 but not of adipoR1 mRNA levels in pigs.

Hypoxia enhances Ecto-5'-Nucleotidase activity and cell surface expression in endothelial cells: role of membrane lipids.

Extracellular adenosine production by the glycosyl-phosphatidyl-inositol-anchored Ecto-5'-Nucleotidase plays an important role in the defense against hypoxia, particularly in the intravascular space. The present study was designed in order to elucidate the mechanisms underlying hypoxia-induced stimulation of Ecto-5'-Nucleotidase in endothelial cells. For this purpose, aortic endothelial cells (SVARECs) were submitted to hypoxic gas mixture. Hypoxia (0% O2 for 18 hours) induced a 2-fold increase of Ecto-5'-Nucleotidase activity (Vmax 19.78+/-0.53 versus 8.82+/-1.12 nmol/mg protein per min), whereas mRNA abundance and total amount of the protein were unmodified. By contrast, hypoxia enhanced cell surface expression of Ecto-5'-Nucleotidase, as evidenced both by biotinylation and immunostaining. This effect was accompanied by a decrease of Ecto-5'-Nucleotidase endocytosis, without modification of Ecto-5'-Nucleotidase association with detergent-resistant membranes. Finally, whereas cholesterol content was unmodified, hypoxia induced a time-dependent increase of saturated fatty acids in SVARECs, which was reversed by reoxygenation, in parallel to Ecto-5'-Nucleotidase stimulation. Incubation of normoxic cells with palmitic acid enhanced Ecto-5'-Nucleotidase activity and cell surface expression. In conclusion, hypoxia enhances cell surface expression of Ecto-5'-Nucleotidase in endothelial cells. This effect could be supported by a decrease of Ecto-5'-Nucleotidase endocytosis through modification of plasma membrane fatty acid composition.

Lovastatin enhances ecto-5'-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases.

Extracellular adenosine production by the GPI-anchored Ecto-5'-Nucleotidase (Ecto-5'-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5'Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5'-Nu stimulation by HRIs, Ecto-5'-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5'-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5'-Nu and decreased endocytosis of Ecto-5'-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5'-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5'-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5'-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.

Protection of human keratinocyte mtDNA by low-level nitric oxide.

This study was designed to evaluate the DNA damaging effects of nitric oxide and to determine whether the endogenous generation of nitric oxide at low levels in the cell exerts a protective effect against this damage. Damage to mitochondrial and nuclear DNA in normal human epidermal keratinocytes (NHEK) was assessed after treatment of these cells with varying concentrations of S-nitroso-N-acetylpenicillamine, which decomposes to release nitric oxide. The results showed that mitochondrial DNA was more vulnerable to nitric oxide-induced damage than was a similarly sized fragment of the beta-globin gene. To evaluate the effects on DNA damage by pretreatment of cells with low-levels of nitric oxide, NHEK cells were treated with the prodrug V-PYRRO/NO. This agent is metabolized inside these cells and releases small quantities of nitric oxide. The cells then were exposed to damaging amounts of nitric oxide produced by S-nitroso-N-acetylpenicillamine. The results of these studies showed that pretreatment of NHEK cells with V-PYRRO/NO attenuated the mtDNA damage and loss of cell viability produced by exposure to S-nitroso-N-acetylpenicillamine.

[Inhibition of iron-catalyzed oxidative reactions restores mathcing between coronary blood flow and myocardial metabolic demand in type 2 diabetes]. / L'inhibition des réactions oxydantes catalysées par le fer rétablit l'adaptation du débit coronaire à la demande métabolique du myocarde chez les diabétiques de type 2.

In diabetes, endothelium-dependent dilation of large and small coronary arteries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an iron chelator that inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold pressor test and flow increase in angiographically normal epicardial coronary arteries of diabetic patients. This result suggests that nitric oxide could be inactivated by reactive oxygen species. The aim of this study was to assess the effects of deferoxamine on coronary microcirculation vasomotion when myocardial oxygen demand is increased by sympathetic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without any other coronary risk factors, coronary blood flow has been measured using quantitative angiography and intracoronary Doppler at baseline and during a cold pressor test, before and after intravenous administration of 500 mg deferoxamine. Increase in rate-pressure product, an estimate of myocardial metabolic demand, was similar before and after deferoxamine (+21.1 +/- 8.7% vs +20.5 +/- 8.9%, respectively), but coronary blood flow increase was significantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%, respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation between coronary blood flow and rate-pressure product changes before deferoxamine (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary microcirculation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matching between myocardial oxygen demand and coronary blood flow.

Phenomenology, psychosocial correlates, and treatment seeking in major depression and dysthymia of adolescence.

OBJECTIVE: To compare phenomenology, psychosocial correlates, and treatment seeking in DSM-Itt-R major depression and dysthymia among adolescents diagnosed as cases in a community-based study. METHOD: A self-report questionnaire, including psychosocial data, life events, eating behaviors, depressive symptoms, substance use, pathological behaviors, and family and school functioning was administered to a nonselected sample (N = 3,287, 93.2% of targeted population) of adolescents aged 11 to 20 years from several Haute-Marne communities in France in 1988-1989. Subgroups of subjects (n = 205, 84.7% of eligible subjects) were interviewed with a structured diagnostic schedule, and adolescents with major depression (n = 49), dysthymia (n = 21) and controls (n = 135) were compared. RESULTS: Nearly 30% of controls had at least one current symptom of depression. Patterns of affective symptoms were similar in major depression and dysthymia, but significant differences emerged in comorbid conditions (more anxiety disorders, suicidal behaviors, and alcohol intoxications associated with major depression) and stressor at onset (more severe in major depression). Experiences of loss during the prior 12 months were associated with both forms of affective disorder, while poor family relationships were specific correlates of dysthymia. In contrast, peer relationships and pathological behaviors did not differ between depressed subjects and controls. Although psychosocial functioning was significantly impaired in both groups of depressed adolescents, treatment seeking was limited to 34.7% for major depressive subjects and 23.8% for dysthymic subjects. CONCLUSION: The results provide evidence that major depression and dysthymia in adolescence are equally severe but may have distinct patterns in associated factors. Despite free access to health care, the rate of treatment seeking for mood disorders in France is similar to that reported in U.S. studies.

Base excision repair of mitochondrial DNA damage in mammalian cells.

This review of the work from our laboratory describes initial studies in which base excision repair in mtDNA was first seen. It considers the results of experiments in which the substrates for mtDNA repair were identified. The discussion then focuses on studies during which the sequence context for mtDNA damage and repair were explored. Next, it addresses factors that have been identified that influence mtDNA repair. Finally, it summarizes the results of studies that evaluated cell-specific differences in the repair of mtDNA and explored some of the biological consequences of these differences.