Mental health in adolescents with obesity: conflicting views among physicians, a qualitative study.

Mental health issues in adolescents with obesity are multifold, with no explicit screening recommendations. The aim of this research is to explore how this screening is performed by physicians and, thus, how it impacts adolescents' care pathways, offering insights into how to improve it through a qualitative study using interpretative phenomenological analysis. Twenty physicians (non-psychiatrist physicians and child and adolescent psychiatrists) involved at various stages in the care pathway were interviewed with semi-structured questionnaires. The findings connect 2 meta-themes. Non-psychiatrist physicians perceive widespread but ill-defined suffering in adolescents with obesity. Non-psychiatrist physicians see screening for mental conditions as mandatory. Unlike child and adolescent psychiatrists, they are not experts in distinguishing psychosocial suffering from psychiatric disorders. Screening is clinical. Adolescents' demand to lose weight in a context of shaming and alexithymia limits their access to psychiatric care. Child and adolescent psychiatrists then redefine the medical response to polymorphous symptoms. Psychiatric diagnoses mainly involve anxiety and depression symptoms, seldom eating disorders.    Conclusion: Physicians have overtly conflicting perspectives over the intensity of mental conditions. Non-psychiatrists, sensitive to perceived distress, seek to have it quickly appraised if they detect a significant suffering. Child and adolescent psychiatrists find appraisal complex to perform in the absence of means, interest, and/or experience. Improving screening requires training health professionals and using multidisciplinary assessment means. What is Known: • Mental health and eating disorders are contributing factors of obesity but their relationship remains complex between cause and consequence. • Mental health conditions and psychosocial suffering are the main complications among adolescents suffering from obesity with guilt, sadness, or stigma. What is New: • Non-psychiatric physicians express their need of a specialized diagnosis to define this suffering, but the lack of availability of psychiatrists and the necessity of time and of a multidisciplinary team lead to a delayed assessment. • For psychiatrists, this suffering is often not a psychiatric condition. Though requiring attention, this can lead to a misunderstanding between professionals.

Towards the development of a new generation of whole-cell bioreporters to sense iron bioavailability in oceanic systems-learning from the case of Synechococcus sp. PCC7002 iron bioreporter.

Whole-cell bioreporters are genetically modified micro-organisms designed to sense bioavailable forms of nutrients or toxic compounds in aquatic systems. As they represent the most promising cost-efficient tools available for such purpose, engineering and use of bioreporters is rapidly growing in association with wide applicability. Bioreporters are urgently needed to determine phytoplankton iron (Fe) limitation, which has been reported in up to 30% of the ocean, with consequences affecting Earth's global carbon cycle and climate. This study presents a critical evaluation and optimization of the only Cyanobacteria bioreporter available to sense Fe limitation in marine systems (Synechococcus sp. PCC7002). The nonmonotonic biphasic dose-response curve between the bioreporters' signal and Fe bioavailability impairs an appropriate data interpretation, highlighting the need for new carefully designed bioreporters. Here, limitations under low Fe concentrations were related to cellular energy stress, nonlinear expression of the targeted promoter and siderophore expression. Furthermore, we provide critical standard criteria for the development of new Fe bioreporters. Finally, based on gene expression data under a range of marine Fe concentrations, we propose novel sensor genes for the development of new Cyanobacteria Fe bioreporters for distinct marine regions.

Formulation and Characterization of Conjugate Vaccines to Reduce Opioid Use Disorders Suitable for Pharmaceutical Manufacturing and Clinical Evaluation.

This study focused on formulating conjugate vaccines targeting oxycodone and heroin for technology transfer, good manufacturing practice (GMP), and clinical evaluation. Lead vaccines used the highly immunogenic carrier protein keyhole limpet hemocyanin (KLH), which poses formulation problems because of its size. To address this barrier to translation, an oxycodone-based hapten conjugated to GMP-grade subunit KLH (OXY-sKLH) and adsorbed on alum adjuvant was studied with regard to carbodiimide coupling reaction time, buffer composition, purification methods for conjugates, conjugate size, state of aggregation, and protein/alum ratio. Vaccine formulations were screened for post-immunization antibody levels and efficacy in reducing oxycodone distribution to the brain in rats. While larger conjugates were more immunogenic, their size prevented characterization of the haptenation ratio by standard analytical methods and sterilization by filtration. To address this issue, conjugation chemistry and vaccine formulation were optimized for maximal efficacy, and conjugate size was measured by dynamic light scattering prior to adsorption to alum. An analogous heroin vaccine (M-sKLH) was also optimized for conjugation chemistry, formulated in alum, and characterized for potency against heroin in rats. Finally, this study found that the efficacy of OXY-sKLH was preserved when co-administered with M-sKLH, supporting the proof of concept for a bivalent vaccine formulation targeting both heroin and oxycodone. This study suggests methods for addressing the unique formulation and characterization challenges posed by conjugating small molecules to sKLH while preserving vaccine efficacy.

An overview of the safety pharmacology career of Dr. C.R. Hassler.

Each year the Safety Pharmacology Society (SPS) recognizes an investigator who has had a marked impact upon the discipline. The 2016 recipient of the SPS Distinguished Service Award (DSA) was Dr. Craig R. Hassler. Dr. Hassler is one of the founding members of the SPS and has been actively engaged in physiological research for over 46years. Dr. Hassler delivered a talk entitled "My 43Years at Battelle Memorial Institute" to meeting attendees. In this article an overview is provided of the illustrious career of Dr. Hassler along with an account of the numerous animal models that were developed at Battelle under his guidance over the years.

Risk factors for substances use and misuse among young people in France: What can we learn from the Substance Use Risk Profile Scale?

BACKGROUND: The prevention of addictions in young people is a challenge for Mental and Public Health policies, and requires specific risk-screening tools. Specific personality traits, as assessed using the Substance Use Risk Profile Scale (SURPS), could play a key role in the onset and escalation of substance use. This study aimed to examine (1) measurement invariance across age and gender (2) the effects of age and gender on associations between SURPS scores and the most frequently-consumed substances. METHODS: Analyses were based on the responses from 5069 participants (aged 14-20 years) from the 2011 ESPAD-France dataset. Substance-use outcomes were experimentation and current frequency of alcohol, tobacco and cannabis use, and drunkenness. RESULTS: Our approach, consisting in analysing measurement and structural invariance and interaction terms, established the stability of (i) SURPS profiles, and (ii) relationships between these scores and substance experimentation and use over a developmental period ranging from mid-adolescence to early adulthood. Measurement invariance across genders was also confirmed despite the absence of scalar invariance for 2 items. Significant interactions between gender and SURPS factors were established, highlighting differential vulnerability, especially concerning Hopelessness and experimentation of alcohol and drunkenness, or Impulsivity and tobacco experimentation. Finally, Anxiety Sensitivity could be protective against substance use, especially for cannabis in girls. CONCLUSIONS: Our results suggest the relevance of the SURPS to assess vulnerability towards drug use, and underline the need to consider gender differences in addiction risks.

Parental alcohol dependence, socioeconomic disadvantage and alcohol and cannabis dependence among young adults in the community.

We tested the hypothesis that socioeconomic disadvantage exacerbates the intergenerational transmission of substance dependence. Among 3056 community-based young adults (18-22 years, 2007), the prevalence of alcohol dependence (WHO AUDIT, 5.8%) and cannabis dependence (DSM IV criteria, 7.3%) was doubled in the presence of combined parental alcohol dependence and socioeconomic disadvantage.

Mechanical characterization of neural electrodes based on PDMS-parylene C-PDMS sandwiched system.

Manufacturing of neural electrodes based on metal foil and silicone rubber using a laser is a simple and promising method. A handicap of such electrode arrays is the mechanical robustness of the thin metal tracks that connect the electrode sites with the interconnection pads. Embedding of structured parylene C foil in silicone rubber turned out to be an interesting method to increase the robustness. Test samples with 12.5 µm thick platinum tracks and a 15 µm thick embedded and RIE-structured parylene C foil showed more than 800 % higher ultimate strength until breakage of the tracks. Different structured parylene C foil showed increasing robustness with increasing hole-spacing.

Bioavailability of trace metals to aquatic microorganisms: importance of chemical, biological and physical processes on biouptake.

An important challenge in environmental biogeochemistry is the determination of the bioavailability of toxic and essential trace compounds in natural media. For trace metals, it is now clear that chemical speciation must be taken into account when predicting bioavailability. Over the past 20 years, equilibrium models (free ion activity model (FIAM), biotic ligand model (BLM)) have been increasingly developed to describe metal bioavailability in environmental systems, despite the fact that environmental systems are always dynamic and rarely at equilibrium. In these simple (relatively successful) models, any reduction in the available, reactive species of the metal due to competition, complexation or other reactions will reduce metal bioaccumulation and thus biological effects. Recently, it has become clear that biological, physical and chemical reactions occurring in the immediate proximity of the biological surface also play an important role in controlling trace metal bioavailability through shifts in the limiting biouptake fluxes. Indeed, for microorganisms, examples of biological (transport across membrane), chemical (dissociation kinetics of metal complexes) and physical (diffusion) limitation can be demonstrated. Furthermore, the organism can employ a number of biological internalization strategies to get around limitations that are imposed on it by the physicochemistry of the medium. The use of a single transport site by several metals or the use of several transport sites by a single metal further complicates the prediction of uptake or effects using the simple chemical models. Finally, once inside the microorganism the cell is able to employ a large number of strategies including complexation, compartmentalization, efflux or the production of extracellular ligands to minimize or optimize the reactivity of the metal. The prediction of trace metal bioavailability will thus require multidisciplinary advances in our understanding of the reactions occurring at and near the biological interface. By taking into account medium constraints and biological adaptability, future bioavailability modeling will certainly become more robust.

Susceptibility of Borna disease virus to the antiviral action of gamma-interferon: evidence for species-specific differences.

Borna disease virus (BDV) infection in its predominant natural host - horses and sheep - leads to fatal meningoencephalomyelitis. The immune-mediated disease can also be induced experimentally in rats following intra- cerebral BDV infection. Despite a vigorous immune response, BDV persists in the central nervous system (CNS) in surviving rats. However, immunization of rats with BDV-specific T-cells prior to challenge with BDV prevents neurological disease and results in virus clearance from the CNS. To analyze whether interferon gamma (IFNgamma) might contribute to viral clearance in the rat brain, we tested the susceptibility of BDV to the antiviral action of rat IFNgamma using different rat cell lines. Even at high concentrations of IFNgamma, BDV infection of astrocyte and fibroblast cell lines as well as of rat embryo cells could not be inhibited efficiently. Similarly, infection of cultured rat hippocampal slices with BDV was not inhibited by rat IFNgamma. In contrast, de novo BDV infection of monkey kidney cells as well as human oligodendroglial cells was blocked by preincubation with human IFNgamma. Furthermore, IFNgamma reduced the BDV load in persistently BDV-infected human oligodendroglial cells but not in infected rat astrocytes. These data suggest species-specific differences in the susceptibility of BDV to the antiviral action of IFNgamma.

What are the characteristics of adolescent hospitalized suicide attempters?

AIM: To study the specificity of hospitalized adolescent suicide attempters. METHOD: Among a national sample of students (n = 11,718, mean age = 16.6 years) studied in 1999, 9.2% (n = 1078) made at least one suicide attempt during their life (SA); 21.9% (n = 234) of them were hospitalized (HSA). We identified the risk factors (family, school, behavioral and psychological) of SA and HSA by comparing (by gender) a) suicide attempters to non-suicide attempters and b) hospitalized suicide attempters to non-hospitalized suicide attempters. RESULTS: Both for girls and boys, the risk factors for SA varied. However, certain risk factors, particularly depressive mood, low self-esteem and poor parent-child relationships, were not associated with hospitalization. Hospitalized suicide attempters had more personal and social problems. But there is an important difference according to gender: in boys, hospitalization is related to physical fighting (OR = 2.2) and offences (OR = 3.4), in girls to running away (OR = 1.7), consumption of illegal drugs other than cannabis (OR = 2.0), having a living standard outside average (OR = 2.0) and going to a private school (OR = 1.7). CONCLUSION: Suicide attempters with problem behavior are more at risk of being hospitalized than others. However, the difference between hospitalized and non-hospitalized subjects was smaller than expected.

Evidence for use of chemical cues by male horseshoe crabs when locating nesting females (Limulus polyphemus).

Horseshoe crabs come ashore in attached pairs during spring high tides to mate and nest on beaches of the Atlantic and Gulf coasts. Unattached males also come ashore and crowd around the nesting pairs as satellites and engage in sperm competition with the attached male. Females with no satellites and females with large numbers of satellites nest next to one another on the same tide. When females are removed and replaced by a cement model, satellite males continue to be attracted to the same location. Models over sites where females with many satellites had nested are more attractive to males than sites from which a female with no satellites had been removed or a site where no crab had been nesting recently. A second experiment demonstrated that males are responding to chemical cues. A sponge filled with seawater taken from below a female with many satellites and placed under a model female was more attractive to males than a sponge filled with seawater. This is the first demonstration that horseshoe crabs use chemical cues, in addition to visual cues, to locate mates.

Conformational study of the intramolecular diels-alder reaction of a pentadienyl acrylate. Theoretical evaluation of kinetic and thermodynamic control

Acrylate 4, prepared from diacetylrhamnal, underwent intramolecular Diels-Alder cycloaddition to give the thermodynamically disfavored trans-fused gamma-lactone 15 as the major product, along with two stereoisomeric cycloadducts. A computational analysis of each of the four transition states arising from 4 and the corresponding cycloadducts permits an understanding of the contrasting requirements for kinetic versus thermodynamic control of the reaction.

Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats.

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.

Influence of vinblastine on DNA parameters and multidrug resistance in renal cell carcinoma in vitro.

The purpose of this study was to investigate how the vinca alkaloid vinblastine influences DNA parameters and the mechanisms of multidrug resistance in renal cell carcinoma. After exposing cell cultures of human renal carcinoma to progressively increasing concentrations of vinblastine the cell lines were examined by flow cytometric DNA analysis to assess the S-phase and G2/M-phase fraction and by a modified MTT assay. It was shown that the exposed cells became P-glycoprotein-positive by staining the cells with a monoclonal antibody (JSB-1). The flow cytometric analysis revealed, with prolonged vinblastine exposure, correlated increases in the S-phase and G2/M-phase fractions (P = 0.0001). When vinblastine-free medium was used for culturing, the changed DNA characteristics returned to their original values. Comparing the DNA parameters with the IC50 (concentration when cell growth is inhibited by 50%) we found a strong correlation between these parameters (P = 0.0001). In conclusion, DNA analysis of long-term vinblastine exposure may provide insight into events leading to multidrug resistance. Furthermore, analysis of the DNA profile might also be an important investigation before planning therapy with vinblastine for renal cell carcinoma.

Self-reported health and behavioral problems among adolescent victims of rape in France: results of a cross-sectional survey.

OBJECTIVES: To measure the prevalence rate of rape among French adolescents; to analyze the associated health and behavioral problems; to analyze the use of the health care system by rape victims. METHOD: A national representative sample of 8,140 students attending public secondary schools in France (grades 8 to 12) filled in a self-administered questionnaire (274 questions) on health and behavior problems (acceptance rate = 87%). Each rape victim in the sample (n = 61) was matched to two nonvictims (n = 122). RESULTS: The reported prevalence rate of rape was .8% (.9% among girls, .6% among boys). For both boys and girls, there was a relationship between rape and current sleep difficulties, depressive symptoms, somatic complaints, tobacco consumption, and behavior problems (running away, violent behavior, stealing, and school absenteeism). Additional problems were associated for boy rape victims: attempted suicide, regular use of alcohol and of illicit drugs. Rape victims did consult health professionals, but the majority saw neither a mental health specialist nor a social worker. CONCLUSION: The findings indicate that rape victims, especially boys, have more behavior problems and health problems than nonrape victims. Authors suggest that adolescents who have ran away from home, attempted suicide, or manifested violent behavior should be systematically asked about rape.

Amino acid handling in uremic rats: citrulline, a reliable marker of renal insufficiency and proximal tubular dysfunction.

The kidney is involved in amino acid reabsorption and metabolism; consequently, in renal insufficiency, these important functions are disturbed, as has been reported in animals and patients. In a first experimental series, rats were subjected to degrees of nephrectomy (NX) varying between 10% and 90%. Three weeks later, amino acid levels were measured in plasma to correlate the levels with the degree of NX. The results indicate that in the range of 33% to 74% NX, the plasma concentration of only three to four amino acids was modified, whereas in rats with 84% NX, the concentration of 11 amino acids was disturbed, compared with sham-operated rats. Citrullinemia was enhanced in uremic rats and correlated with the degree of NX. More interestingly, citrullinemia was increased in the range of 10% to 33% NX without any changes in uremia and creatininemia, two well-known markers of uremic states. A second experimental series was designed to study the time course of changes in aminoacidemia to find a marker for the onset of renal failure. Rats were subjected to 36% NX for a period of 1 to 21 days. Uremia and creatininemia peaked 24 to 48 hours after NX, and creatinine clearance (Clcreat) concomitantly diminished. Unfortunately, these three markers of uremic states returned to control values during the next few days before increasing during the last 2 weeks. In contrast, citrullinemia increased twofold 48 hours after NX and plateaued over the next 20 days. We conclude that in rats, citrullinemia could be used (1) to detect acute and chronic renal failure, (2) as a specific marker of normal function of the proximal tubule, and (3) to estimate the degree of renal damage. From this study, renal insufficiency might be easily detected by measuring citrullinemia.

Cyclic AMP is a hepatorenal link influencing natriuresis and contributing to glucagon-induced hyperfiltration in rats.

The effects of glucagon (G) on proximal tubule reabsorption (PTR) and GFR seem to depend on a prior action of this hormone on the liver resulting in the liberation of a mediator and/or of a compound derived from amino acid metabolism. This study investigates in anesthetized rats the possible contribution of cAMP and urea, alone and in combination with a low dose of G, on phosphate excretion (known to depend mostly on PTR) and GFR. After a 60-min control period, cAMP (5 nmol/min x 100 grams of body weight [BW]) or urea (2.5 micromol/min x 100 grams BW) was infused intravenously for 200 min with or without G (1.2 ng/min x 100 grams BW, a physiological dose which, alone, does not influence PTR or GFR). cAMP increased markedly the excretion of phosphate and sodium (+303 and +221%, respectively, P < 0.01 for each) but did not alter GFR. Coinfusion of cAMP and G induced the same tubular effects but also induced a 20% rise in GFR (P < 0.05). Infusion of urea, with or without G, did not induce significant effects on PTR or GFR. After G infusion at increasing doses, the increase in fractional excretion of phosphate was correlated with a simultaneous rise in plasma cAMP concentration and reached a maximum for doubling of plasma cAMP. These results suggest that cAMP, normally released by the liver into the blood under the action of G, (a) is probably an essential hepatorenal link regulating the intensity of PTR, and (b) contributes, in conjunction with specific effects of G on the nephron, to the regulation of GFR.

Renal synthesis of arginine in chronic renal failure: in vivo and in vitro studies in rats with 5/6 nephrectomy.

Synthesis of arginine (Arg) from citrulline (Cit) by the kidney is a major source of Arg for the body. The high level of plasma Cit in chronic renal failure is often thought to result from the impairment of the renal conversion of Cit to Arg. To verify this assumption, we performed two studies in Sprague-Dawley rats with 5/6 nephrectomy (CRF rats) and in sham-operated rats (CONT rats). In study I synthesis of Arg by isolated proximal convoluted tubules (PCT; the nephron segment exhibiting the highest Arg synthesis) was measured in vitro with two concentrations of Cit (200 or 50 microM) corresponding to those observed in plasma of rats with or without renal failure. In study II the net renal uptake of Cit and release of Arg were determined in vivo by measuring PAH clearance and arterial and renal venous Arg, and Cit concentrations in anesthetized rats. The in vitro results showed that Arg synthesis increased only in proportion to the hypertrophy of remnant PCT (+50%), and was highly and similarly dependent on Cit concentration in PCT of remnant and normal kidneys (Arg production with 200 microM Cit was 3 times higher than with 50 microM Cit for both CONT and CRF). The in vivo results showed that renal Cit uptake and Arg release were not altered in CRF: -286 +/- 28 versus -326 +/- 16 nmol Cit.min-1 (NS), and + 390 +/- 47 versus + 399 +/- 22 nmol Arg.min-1 (NS) in CONT and CRF rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Plastic-metal bonding by the help of a silanizable silicatic porcelain layer for fusing to metal]. / Plast-Metall-Verbund unter Einsatz eines silanisierbaren silikatischen Aufbrennmaterials.

The use of Keramail (Keradenta/Wilde GmbH Radeberg) for fusing silicatic layers to metallic frameworks in a preheating furnace and the later on silianizing in order to bond teeth coloured veneering materials has proved laboratory and chemically. On the base of shearing tests with selected precious and non precious alloys the good bonding strength of this bonding system in comparison with the Silicoater-system is shown.