The partial skeleton StW 431 from Sterkfontein – Is it time to rethink the Plio-Pleistocene hominin diversity in South Africa?

The discovery of the nearly complete Plio-Pleistocene skeleton StW 573 Australopithecus prometheus from Sterkfontein Member 2, South Africa, has intensified debates as to whether Sterkfontein Member 4 contains a hominin species other than Australopithecus africanus. For example, it has recently been suggested that the partial skeleton StW 431 should be removed from the A. africanus hypodigm and be placed into A. prometheus. Here we re-evaluate this latter proposition, using published information and new comparative data. Although both StW 573 and StW 431 are apparently comparable in their arboreal (i.e., climbing) and bipedal adaptations, they also show significant morphological differences. Surprisingly, StW 431 cannot be unequivocally aligned with either StW 573 or other hominins from Sterkfontein commonly attributed to A. africanus (nor with Paranthropus robustus and Australopithecus sediba). This finding, together with considerations about the recent dating of Plio-Pleistocene hominin-bearing sites in South Africa and palaeoecological/palaeoclimatic conditions, raises questions whether it is justified to subsume hominins from Taung, Makapansgat and Sterkfontein (and Gladysvale) within a single taxon. Given the wealth of fossil material and analytical techniques now available, we call for a re-evaluation of the taxonomy of South African Plio-Pleistocene hominins. Such an endeavour should however go beyond the current (narrow) focus on establishing an A. africanus-A. prometheus dichotomy. Macho, Gabriele A. Fornai, Cinzia Tardieu, Christine Hopley, Philip Haeusler, Martin Toussaint, Miche

Journal für Klinische Endokrinologie und Stoffwechsel / Jenseits von Hormonen und Wachstum psychosoziale Hürden bei Turner-Syndrom

(VLID)364757

Care of girls and women with Turner syndrome: beyond growth and hormones

Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial phenotype. Given the complexity of the condition, patients face manifold difficulties which increase over the lifespan. Furthermore, failures during the transitional phase to adult care result in moderate health outcomes and decreased quality of life. Guidelines on the optimal screening procedures and medical treatment are easy to find. However, recommendations for the treatment of the incriminating psychosocial aspects in TS are scarce. In this work, we first reviewed the literature on the cognitive and psychosocial development of girls with TS compared with normal development, from disclosure to young adulthood, and then introduce a psychosocial approach to counseling and treating patients with TS, including recommendations for age-appropriate psychological diagnostics. With this work, we aim to facilitate the integration of emphasized psychosocial care in state-of-the-art treatment for girls and women with TS

Acceleration in BMI gain following COVID-19 restrictions. A longitudinal study with 7- to 10-year-old primary school children

Background: The ramifications of COVID-19 restrictions might accelerate the already rising proportion of children with overweight or obesity. Objectives: To assess the association between COVID-19 restrictions and changes in body mass index (BMI) and the proportion of children with overweight or obesity. Methods: Cohort study with baseline measurements in September 2019 (prior to COVID-19 restrictions) and follow-up in June 2020, September 2020, and March 2021 at 12 primary schools in Austria. The height and weight of 738 children aged 7 to 10 years were measured and age- and sex-specific national and international standardized values were calculated. Changes over time were analysed by analysis of variance. Results: Mean BMI IOTF standard deviation scores (SDS) increased by 0.24 (95% CI, 0.21–0.28) between September 2019 and March 2021. The proportion of children with overweight or obesity increased from 20.7% to 26.2% during this period (p < 0.001) using national reference values—EQUI BMI AUT—comparable results were observed. Simultaneously, the height AUT SDS increased by 0.06 (95% CI, 0.05–0.08) with a larger increase in girls (+0.11; p < 0.001) than in boys (+0.03; p = 0.19). Conclusions: COVID-19 restrictions were associated with accelerated increases in mean BMI and the proportion of children with overweight or obesity. The increase in height SDS in girls calls for further investigations

Primary Growth Hormone (GH) Insensitivity and Insulin-Like Growth Factor Deficiency Caused by Novel Compound Heterozygous Mutations of the GH Receptor Gene: Genetic and Functional Studies of Simple and Compound Heterozygous States

International audienceContext: Primary GH insensitivity (GHI) or Laron syndrome, caused by mutations of the GH receptor (GHR) gene, has a clinical phenotype of postnatal growth failure associated with normal elevated serum concentrations of GH and low serum levels of IGF-I.Objective: We investigated the clinical and biochemical implications of molecular defects in the GHR gene in an Austrian family with two daughters who were GHI.Patients: Patient 1 [height, -4.8 sd score (SDS)] and patient 2 (height, -5.0 SDS) had elevated circulating levels of GH, low-normal levels of GH-binding protein, and abnormally low IGF-I (-5.0 SDS and -2.6 SDS, respectively) and IGF-binding protein-3 (-2.6 SDS and -2.0 SDS, respectively).Results: Both patients carry novel compound, missense, heterozygous GHR mutations, C94S and H150Q. In vitro reconstitution experiments demonstrated that whereas each of the mutants could be stably expressed, GHR(C94S) lost its affinity for GH and could neither activate signal transducer and activator of transcription (STAT)-5b nor drive STAT5b-dependent gene transcription in response to GH (1-100 ng/ml). GHR(H150Q) showed normal affinity for GH but impaired capacity for signal transduction. The compound heterozygote and C94S heterozygote, but not the H150Q heterozygote, showed significant deficiency in activating GH-induced gene expression, corroborating diminished GH-induced STAT5b activation in fibroblasts carrying GHR(C94S) as either a compound heterozygote (in the patients) or a simple heterozygote (in one parent).Conclusions: Each of the compound heterozygous mutations contributed additively to the pathological condition seen in the patients, and the more detrimental of the two mutations, C94S, may cause (partial) primary GHI, even in a heterozygous state

The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES)

The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES) was investigated. We analyzed 120 patients registered into the European Ewing Tumor Working Initiative of National Groups (EURO-E.W.I.N.G. 99) trial at the trial center of Muenster from 1998 to 2006. Median age was 16.2 years. Local treatment of the primary tumor was surgery in 26 of 120 patients, surgery and radiotherapy in 21 patients, and definitive radiotherapy in 40 patients. For treatment of metastases, 6 of 120 patients received surgery; 9 patients, surgery and radiotherapy; and 33 patients, definitive radiotherapy. Forty-seven (39%) patients had local treatment of both the primary tumor and metastases, 41 (34%) patients of either the primary tumor or metastases, and 32 (27%) received no local therapy. Event-free survival (EFS) at 3 years was 0.24 (95% CI, 0.16-0.33). Univariate analyses demonstrated the impact of local therapy given to the primary tumor: 3-year EFS was 0.25 with surgery, 0.47 with surgery and radiotherapy, 0.23 with radiotherapy, and 0.13 when no local therapy was administered (P < .001). Three-year EFS in PDMES was also influenced by the local treatment: surgery, 0.33; surgery and radiotherapy, 0.56; radiotherapy, 0.35; no local therapy, 0.16 (P = .003). Three-year EFS was 0.39 in patients who received local treatment of both primary tumor and PDMES, compared with 0.17 in patients with any local treatment of either primary tumor or PDMES and 0.14 in patients with no local therapy (P < .001). Multivariate analysis showed absence of local treatment to be the major risk factor (HR = 2.21; P = .027; n = 20). Local therapy of involved sites is important for patients with PDMES and should complement systemic treatment whenever possibl

Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone

International audienceAbstract Background X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies. Results Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH) 2 D increased dramatically under burosumab therapy. Conclusion To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

<div><p>Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown <i>in vitro</i> as well as <i>in vivo</i> to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.</p></div

Proliferation effects of MGF/IGF-1.

<p>Effects of IGF-1, different MGF peptides and their combination on proliferation of porcine growth plate chondrocytes as measured by BrdU staining. (n = 5–11 per group; One-way ANOVA of log-transformed data, Games-Howell post-hoc analyses: * p<0.05; ** p<0.01; *** p<0.001 vs respective untreated control; Data are shown as mean + SEM).</p

<i>Mgf</i> and <i>Igf1</i> mRNA expression profile (normalized to 18S rRNA) of various porcine tissue samples (A) and within different zones of the growth plate separated by laser capture microdissection (B) as quantified by real-time PCR.

<p>(n≥3 per tissue, One-way ANOVA of log-transformed data (a) or Kruskal-Wallis with Bonferroni-adjusted post-hoc tests (b) were used to detect differences between groups: ** p<0.01; ***p<0.001 vs proliferative chondrocytes; ^###p<0.001 vs hypertrophic chondrocytes. Data are presented as mean + SEM).</p