Produktdiversifikation und Profitabilität der deutschen Ernährungswirtschaft: Eine theoretische und empirische Betrachtung.

Auf der Basis des Struktur-Verhalten-Ergebnis-Ansatzes kann Diversifikation in ihrer Wirkung als Markteintrittsbarriere verstanden werden und hat als solche einen positiven Einfluss auf die Profitabilität der diversifizierten Unternehmen. Im Rahmen dieser Arbeit wird auf der Basis der vom Statistischen Bundesamt zu 4-stelligen Wirtschaftszweigen aggregierten Daten für den Zeitraum 1977 bis 1994 der Einfluss der Produktdiversifikation auf die Profitabilität von 25 Branchen des deutschen Ernährungsgewerbes untersucht. Es kann ein positiver Einfluss der Diversifikation auf die Profitabilität festgestellt werden. -- Using the structure-conduct-performance approach it can be argued that diversification raises barriers to entry which have a positive influence on the profitability of firms. This study examines the effect of product diversification on the profitability of 25 German food industry sectors from 1977 to 1994. The analysis reveals a positive effect of diversification on the profitability of industries.Struktur-Verhalten-Ergebnis-Ansatz,Produktdiversifikation,Ernährungswirtschaft,Profitabilität,Panelanalyse,structure-conduct-performance approach,product diversification,food industry,profitability,panel data analysis

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Germline mutations in the tumor suppressor gene PTEN cause PTEN Hamartoma Tumor Syndrome (PHTS). Pediatric patients with PHTS frequently develop lipomas. Treatment attempts with the mTORC1 inhibitor rapamycin were unable to reverse lipoma growth. Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. Here, we tested whether alpelisib has growth-restrictive effects and induces cell death in lipoma cells. We used PTEN-haploinsufficient lipoma cells from three patients and treated them with alpelisib alone or in combination with rapamycin. We tested the effect of alpelisib on viability, proliferation, cell death, induction of senescence, adipocyte differentiation, and signaling at 1–100 M alpelisib. Alpelisib alone or in combination with rapamycin reduced proliferation in a concentrationand time-dependent manner. No cell death but an induction of senescence was detected after alpelisib incubation for 72 h. Alpelisib treatment led to a reduced phosphorylation of AKT, mTOR, and ribosomal protein S6. Rapamycin treatment alone led to increased AKT phosphorylation. This effect could be reversed by combining rapamycin with alpelisib. Alpelisib reduced the size of lipoma spheroids by attenuating adipocyte differentiation. Since alpelisib was well tolerated in first clinical trials, this drug alone or in combination with rapamycin is a potential new treatment option for PHTS-related adipose tissue overgrowth

Relationship between Age-Dependent Body Constitution and Temporomandibular Joint Sounds in Adolescents

To date, risk factors for temporomandibular joint (TMJ) sounds are still not completely understood, and anatomical factors are suspected to influence their occurrence. This study aimed to evaluate the impact of body constitution on temporomandibular joint sounds of adolescents. 10- to 18-year-old participants of the LIFE Child Study were examined for TMJ sounds, and physical parameters such as body height, body weight, and general laxity of joints were measured. Odds ratios (OR) for associations of TMJ sounds and standard deviation scores (SDS) of body height and body weight were calculated by using binary logistic regression, including cofactors such as age and number of hypermobile joints. The OR for TMJ sounds and SDS of body height was 1.28 (95% confidence interval (CI) 1.06; 1.56) in females when the age-adjusted height value was above 0. SDS of body weight indicated significant ORs for TMJ sounds in males with values of 0.81 (95% CI 0.70; 0.94). No correlation was detected for SDS values and TMJ crepitus. Tall female adolescents seem to be more prone to TMJ clicking sounds, while their occurrence seems less likely in male adolescents with higher body weight

FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children: relevance of FTO variants to defend body weight in lean children?

Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. Conclusion: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children

The Influence of Steroid Hormones on Tooth Wear in Children and in Adolescents

(1) Background: From a young age, boys are more often affected by tooth wear than girls. This suggests an influence of the male sex hormone (testosterone) on the aetiology of tooth wear. The aim of the present study was to investigate the incidence of tooth wear in relation to steroid hormone levels in children. (2) Methods: 1022 test persons aged between 10 and 18 (491 male, 531 female) from the LIFE Child study underwent medical and dental examination. Tooth wear was measured through clinical inspection. Blood samples were taken to determine hormone levels (testosterone, SHBG). The level of free testosterone was calculated from the ratio of testosterone to SHBG. Using multivariable methods, the incidence of tooth wear was analyzed as a function of hormone levels, while controlling for confounders such as age, sex, social status, and orthodontic treatment. (3) Results: The incidence of tooth wear increased with age in both sexes. Boys showed significantly more often attrition facets than girls (17.5% vs. 13.2%, p < 0.001). Subjects with tooth wear showed significantly higher free testosterone levels than those without (males: p < 0.001, females: p < 0.05). After controlling for confounding variables, the risk of tooth wear increased by approximately 30.0% with each year of life (odds ratio [OR]boys = 1.29, 95% confidence interval [CI] = 1.04–1.56; [OR]girls = 1.32, 95% CI = 1.08–1.61). In addition, the risk of tooth wear increased by 6.0% per free testosterone scale score only in boys (OR = 1.06, 95% CI = 1.01–1.12). (4) Conclusions: Tooth wear is common in children and in adolescents, and it increases steadily with age in both sexes. The stronger increase and the higher prevalence among male adolescents can be explained by the additional effect of free testosterone

Simvastatin induces apoptosis in PTEN‑haploinsufficient lipoma cells

Adipose tissue tumors (lipomas) frequently develop in patients with heterozygous germ line phosphatase and tensin homolog (PTEN) mutations. simvastatin has been demonstrated to exhibit antitumor effects, and so the aim of the present study was to assess the effects of simvastatin on the growth of human PTEN haploinsufficient lipoma cells. Whether the effects of simvastatin in lipomas are mediated via PTEN upregulation was also assessed. The results of the present study revealed that simvastatin treatment reduced cell viability and induced apoptosis in human lipoma cells. Furthermore, it was demonstrated that the expression of cellular PTEN mRNA and protein was increased following simvastatin stimulation. In addition, the phosphorylation of protein kinase B and downstream targets of mammalian target of rapamycin and 4E‑binding protein (4E‑BP)‑1 was attenuated. It was also demonstrated that simvastatin induced PTEN transcriptional upregulation by increasing peroxisome proliferator‑activated receptor (PPAR)γ expression. The small interfering RNA‑mediated knockdown of PPARγ abrogated the stimulatory effect of simvastatin on the PTEN protein, but did not influence apoptosis. The results of the present study suggest that simvastatin may be beneficial for patients with inoperable PTEN haploinsufficient lipomas

Harmonization of growth hormone measurements with different immunoassays by data adjustment

Background: The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. Methods: In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tubingen). Results: The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean +/- SD) of values within the cut-off range was 24.3%+/- 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and &lt; 1%, respectively. Conclusions: hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence

Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/ duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boy

Biological Significance of Anti-GH Antibodies in Children Treated with rhGH

Background: The occurrence of antidrug antibodies is common in children treated with recombinant human growth hormone (rhGH). However, their clinical significance is unclear. Objective: This study aimed to examine the clinical significance of anti-GH antibodies by analyzing the phenotype of patients who tested positive in relation to the quantity of anti-GH antibodies. Method: In this laboratory-based retrospective study encompassing a time span of 6 years, all positive samples were identified, and senders were contacted. Anti-GH antibodies were measured using a radioprecipitation assay; positive samples underwent a confirmatory assay. Results: Out of a total of 104 samples from 66 patients, positive test results were found in 28 samples from 13 patients. Clinical data were available from all but one. The group with positive test results comprised 6 patients with a normal response to GH provocative tests (group A) and 6 with an insufficient response or with isolated GH deficiency (IGHD) type 1A (group B). Diagnoses in group A were neurosecretory dysfunction, bioinactive GH syndrome and constitutional delay of growth and puberty. Diagnoses in group B were IGHD type 1A, septo-optic dysplasia, and cerebral midline defect with multiple pituitary hormone deficiency. Insufficient growth response to rhGH was absent except in one sibling pair with IGHD type 1A and a patient with cerebral midline defect. These patients had the highest concentrations of anti-GH antibodies. Conclusions: The biological significance of anti-GH antibodies seems to be limited to patients with high concentrations of anti-GH antibodies. For all other patients, we recommend a careful “wait and see” strategy and monitoring antibody titers