Lazy Sundays: role of day of the week and reactivity on objectively measured physical activity in older people.

BACKGROUND: The aim of this study was to assess the effect of day of the week and wearing a device (reactivity) on objectively measured physical activity (PA) in older people. METHODS: Walking duration as a measure for PA was recorded from 1333 German community-dwelling older people (≥65 years, 43.8% women) over 5 days using accelerometers (activPAL). Least-square means of PA with 95%-confidence intervals (95%-CI) from multi-level analysis were calculated for each day of the week and each measurement day (days after sensor attachment). RESULTS: Walking duration on Sundays was significantly lower compared to working days (Sunday vs. Monday-Friday: - 12.8 min (95%-CI: - 14.7; - 10.9)). No statistically significant difference compared to working days was present for Saturdays. The linear slope for measurement day and walking duration was marginal and not statistically significant. CONCLUSIONS: Studies using PA sensors in older people should assess Sundays and working days to adequately determine the activity level of the participants.

Simple Categorization of Human Figure Drawings at 5 Years of Age as an Indicator of Developmental Delay.

Purpose: To elucidate the association between developmental stage of human figure drawing(HFD) and fine motor control, visual perception, and further investigate its potential to be used for screening developmental delay. Methods: Participants were 301 children at 5½ years of age, 176 born preterm and 125 at term, whose HFDs were categorized into six developmental stages. Motor-Free-Visual-Perception Test, Movement-ABC, Performance Intelligence Quotient (PIQ: Wechsler Scale), and the Visual-Motor Integration test were used. Fine motor functions were explored using ImageJ. Results: Age-expected HFDs were drawn by 87% of the children, while 13%, mostly preterm boys, drew immature ones. Stages of HFD were related to both PIQ and Movement-ABC. Visuomotor control and visual perception significantly explained the HFD. The sensitivity and specificity of HFD as a screening tool was moderate to good. Conclusions: HFD is influenced by visual perception and visuomotor control and can be used for screening developmental delay at preschool age.

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

AIM: This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. METHODS: Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. RESULTS: Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. CONCLUSION: This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

A porcine model of osteosarcoma.

We previously produced pigs with a latent oncogenic TP53 mutation. Humans with TP53 germline mutations are predisposed to a wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss of p53 function has been observed in >50% of human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert to a transformed phenotype after activation of latent oncogenic TP53(R167H) and KRAS(G12D), and overexpression of MYC promotes tumorigenesis. The process mimics key molecular aspects of human sarcomagenesis. Transformed porcine MSCs exhibit genomic instability, with complex karyotypes, and develop into sarcomas on transplantation into immune-deficient mice. In pigs, heterozygous knockout of TP53 was sufficient for spontaneous osteosarcoma development in older animals, whereas homozygous TP53 knockout resulted in multiple large osteosarcomas in 7-8-month-old animals. This is the first report that engineered mutation of an endogenous tumour-suppressor gene leads to invasive cancer in pigs. Unlike in Trp53 mutant mice, osteosarcoma developed in the long bones and skull, closely recapitulating the human disease. These animals thus promise a model for juvenile osteosarcoma, a relatively uncommon but devastating disease.

[A 31-year-old pregnant woman with refractory hypercalcemia]. / 31-jährige Schwangere mit refraktärer Hyperkalzämie.

A 31-year-old pregnant woman presented with refractory severe hypercalcemia due to an advanced neuroendocrine tumor masquerading as hyperemesis gravidarum. Octreotide therapy and extensive tumor debulking surgery resulted in symptom control. After a prolonged stay in the intensive care unit due to parapneumonic acute respiratory distress syndrome, the patient delivered a healthy child. Neuroendocrine tumors are a rare complication of pregnancy and a seldom cause of refractory hypercalcemia.

[Paul Nitsche: psychiatric reformer and main protagonist of Nazi euthanasia]. / Paul Nitsche - Reformpsychiater und Hauptakteur der NS-"Euthanasie".

The professional career of Paul Nitsche reflects the contradictory path taken by a German institutional psychiatrist who was a leader in the field at the time. During the Weimar Republic he advocated improving the institutional system based on principles of psychiatric reform, but was already receptive to concepts of racial hygiene. Shortly after the National Socialists seized power, Nitsche was already an influential proponent and participant in eugenic measures in Saxony and actively involved in implementing the "Law for the Prevention of Genetically Diseased Offspring." He increasingly appraised the value of a patient according to the person's economic performance. It was also Nitsche's opinion that the consequence of this extreme rationalization of human life was to exterminate "life unworthy of life." As a T4 appointed head assessor he decided in the last instance whether thousands of people would live or die. As the Medical Director of the T4 program, he was later directly responsible for continuing the massacre as "decentralized euthanasia." At the euthanasia trial in Dresden he was condemned to death and executed in 1948.

Gallstone prevalence and risk factors for gallstone disease in an urban population of children and adolescents.

BACKGROUND: At present only a few sonography-based studies have assessed gallstone prevalence and associated risk factors in children and adolescents in randomly selected urban population samples. The aim of the present study was to analyze the prevalence of cholecystolithiasis and associated risk factors in children and adolescents. METHODS: From a randomly selected urban population sample a total of 307 children and adolescents (157 girls, 150 boys; age 12 - 18 years, mean age 15.1 +/- 2.0 years) were studied using ultrasonography, standardized questionnaires and blood samples. RESULTS: Three adolescents (one girl, two boys), corresponding to a prevalence of 1.0 %, showed gallstones. One 14-year-old girl and one 17-year-old boy were overweight using Cole's classification. A positive family history and female gender could not be confirmed as risk factors. CONCLUSION: Obesity appears to be a risk factor in the development of gallstones in childhood and adolescence.

Splenic rupture following endoscopic polypectomy.

A 70-year-old man presented with two medium-sized colon polyps at the office of a gastroenterologist. After endoscopic polypectomy in a hospital, the patient was admitted to another hospital because of collapse and increasing abdominal pain. CT scan revealed hematoperitoneum and splenic subcapsular hematoma. Laparotomy with splenectomy was performed because of extended splenic rupture. The postoperative course was unremarkable except late wound dehiscence.

Glucokinase-activating GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk in the Ludwigshafen Risk and Cardiovascular Health Study.

Two strongly correlated polymorphisms located within the gene of the glucokinase regulator protein (GKRP), rs780094 and rs1260326, are associated with increased plasma triglyceride levels and provide a genetic model for the long-term activation of hepatic glucokinase. Because pharmacological glucokinase activators are evaluated for the treatment of diabetes, the aim of the study was to assess if these polymorphisms could provide evidence for an increased cardiovascular risk of long-term glucokinase activation. Therefore, these polymorphisms were tested in 3 500 patients of the Ludwigshafen Risk and Cardiovascular Health study, which was designed to assess cardiovascular risk factors. The two variants were associated with a significant increase of both plasma triglycerides (p<0.0001) and VLDL triglyceride levels (p<0.0001). Plasma free fatty acid concentrations were also significantly elevated (p<0.0078). LDL and HDL cholesterol levels were unchanged. No association was found with respect to coronary stenosis, myocardial infarction, left ventricular wall hypertrophy, and hypertension. In conclusion, long-term genetic glucokinase activation by the GKRP polymorphisms was not associated with an increased cardiovascular risk in the study population.

C-11 methionine positron emission tomography/computed tomography localizes parathyroid adenomas in primary hyperparathyroidism.

In patients with primary hyperparathyroidism (pHPT), positive preoperative localization studies enable to perform a minimally invasive approach for parathyroid surgery. However, current imaging techniques are not always successful. We therefore conducted a study to determine the sensitivity of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) in localizing parathyroid adenomas in pHPT. Met-PET/CT scans of the neck and mediastinum of 33 patients undergoing parathyroidectomy for primary HPT were compared with intraoperative and histological findings. Primary HPT was caused by a single gland adenoma in 30 patients, while another 3 patients had multiglandular disease. Met-PET/CT scan correctly located a single gland adenoma in 25 out of 30 (83%) patients with pHPT, among them 2 patients with persistent disease, 7 patients with prior neck surgery, and 8 patients with concomitant thyroid nodules. In 3 patients with multiglandular disease, Met-PET/CT showed only one enlarged parathyroid gland in two individuals and was negative in the third patient. Statistical analysis found a significant correlation between true-positive results and the weight (2.42+/-4.05 g) and diameter (2.0+/-1.18 cm) of parathyroid adenomas while the subgroup with false negative findings had significantly smaller (0.98+/-0.54 cm) and lighter (0.5+/-0.38 g) glands. Sensitivity was 83% for single gland adenomas and 67% for multiglandular disease. Met-PET/CT correctly localized 83% of single gland parathyroid adenomas in patients with pHPT. However, preoperative localization of multiglandular disease due to double adenomas or parathyroid hyperplasia remained difficult.

Association between asymmetric dimethylarginine and neopterin in patients with and without angiographic coronary artery disease.

The increase of circulating asymmetric dimethylarginine (ADMA) concentrations, a competitive inhibitor of the nitric oxide synthases, is associated with an increased cardiovascular risk and is considered to play a role in endothelial dysfunction. Recently, ADMA production was observed in stimulated human peripheral mononuclear cells. In this study, we examined a potential relationship between concentrations of ADMA and of the immune activation marker neopterin in patients scheduled for coronary angiography. In a cross-sectional approach, blood concentrations of ADMA, homocysteine, neopterin, folic acid and vitamins B6 and B12 were compared in 2030 patients, which were recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. ADMA concentrations did not differ between patients with coronary artery disease (CAD) (mean +/- SD: 0.82 +/- 0.15 micromol/l) and controls (0.81 +/- 0.14 micromol/l; Welch's t-test: P = n.s.). ADMA concentrations correlated with homocysteine (r(s) = 0.207) and vitamin B6 (r(s) = -0.190), and an even stronger correlation with neopterin (r(s) = 0.276; all P < 0.0001) was observed. In conclusion, increased ADMA concentrations in patients at risk for atherosclerosis are associated with increased neopterin concentrations. Data suggest that immune activation may contribute to increased ADMA production in CAD patients.

MHC-environment interactions leading to type 1 diabetes: feasibility of an analysis of HLA DR-DQ alleles in relation to manifestation periods and dates of birth.

AIM: The region on chromosome 6p21 (IDDM1) confers the largest part of genetic susceptibility to type 1 diabetes (T1D) with particular human leucocyte antigen (HLA) alleles predisposing and others protecting from it. As T1D is primarily a "sporadic" disease, the pathophysiology must involve gene-environment interactions. We searched for indirect evidence for such major histocompatibility complex (MHC)-environment interactions by asking two questions: (i) can the degree of an HLA association vary over time periods? and (ii) if a prenatal event like an intrauterine infection - that might cluster in seasons - leads to differences of HLA associations in patients with particular birth months? METHODS: We screened the Type 1 Diabetes Genetics Consortium (T1DGC) database (in addition our own database and the original UK, US and SCAND databases) for MHC DR-DQ and CTLA4 associations. First, we separated the groups of patients with onset of disease before 1980 in comparison with onset after 1980. Second, we analysed the data according to dates of birth (grouped in months). Not all patients' dates of birth or manifestation periods were available, leading to different group sizes. There were 282 patients analysed for manifestation periods and 329 for birth month. RESULTS: The cohorts of manifestation before 1980 demonstrated a significantly lower frequency of DQ2/X (2 vs. 14.2%; p = 0.03). There was a trend for DQ8/x to be more frequent for manifestations before 1980 (34 vs. 21.6%; p < 0.10). Other alleles did not differ significantly. The months of birth were not evenly distributed. Significant deviations from the whole group were seen in August (DQ2/8 trough and DQx/x high), whereas birth in September was more frequent in DQ8/x or DQ8/8 carriers. This pattern was significantly different from the expected distribution of months at birth (13.9 vs. 7.6%; p < 0.04). CONCLUSIONS: We demonstrate the feasibility of an analysis that searches for indirect evidence of gene-environment interactions. These preliminary data need to be confirmed in larger data sets.

Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are highly resistant to treatment due to changes in various signalling pathways. CK1 isoforms play important regulatory roles in these pathways. AIMS: We analysed the expression levels of CK1 delta and epsilon (CK1delta/in) in pancreatic tumour cells in order to validate the effects of CK1 inhibition by 3-[2,4,6-(trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261) on their proliferation and sensitivity to anti-CD95 and gemcitabine. METHODS: CK1delta/in expression levels were investigated by using western blotting and immunohistochemistry. Cell death was analysed by FACS analysis. Gene expression was assessed by real-time PCR and western blotting. The putative anti-tumoral effects of IC261 were tested in vivo in a subcutaneous mouse xenotransplantation model for pancreatic cancer. RESULTS: We found that CK1delta/in are highly expressed in pancreatic tumour cell lines and in higher graded PDACs. Inhibition of CK1delta/in by IC261 reduced pancreatic tumour cell growth in vitro and in vivo. Moreover, IC261 decreased the expression levels of several anti-apoptotic proteins and sensitised cells to CD95-mediated apoptosis. However, IC261 did not enhance gemcitabine-mediated cell death either in vitro or in vivo. CONCLUSIONS: Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.

CT-guided vertebroplasty in osteoprotic vertebral fractures: incidence of secondary fractures and impact of intradiscal cement leakages during follow-up.

The purpose of this study was to analyse the number and types of secondary fractures, and to investigate the impact of intradiscal cement leaks for adjacent vertebral fractures. Patients with osteoporotic vertebral fractures were treated with vertebroplasty. Results were documented and prospectively followed by means of computed tomography (CT) and magnetic resonance imaging. The frequency and the types of cement leakages were analysed from multiplanar CT images and secondary fractures were characterised as follows: (1) adjacent fracture in the immediate vicinity of an augmented vertebra; (2) sandwich fracture, fracture of an untreated vertebra between two vertebrae that had been previously augmented, and (3) distant fractures not in the vicinity of augmented vertebrae. A total of 385 osteoporotic vertebral fractures were treated in 191 patients (61 men, 130 women, age 70.7 +/- 9.7 years). The overall rate of cement leaks was 55.6%, including all leaks detectable by CT. Intradiscal leaks through the upper, the lower, and both endplates occurred in 18.2%, 6.8%, and 2.6%, respectively. In 39 patients (20.4%), a total of 72 secondary fractures occurred: 30 adjacent fractures in 23 patients (12.0%) with a time to fracture of 2 months [median; 1.0/4.0 months, first/third quartile (Q1/Q3)]; 11 secondary sandwich fractures in 11 patients (5.8%) after 1.5 months (median; 0.25/7.5 months, Q1/Q3); and 31 distant fractures in 20 patients (10.5%) after 5 months (median; 2.0/8.0 months, Q1/Q3). Ten of 30 adjacent fractures occurred in the presence of pre-existing intradiscal cement leaks and 20 where there was no leakage. Six of 11 sandwich fractures occurred in the presence of intradiscal leaks (five leaks in both adjacent disc spaces, one leak in the lower disc space) and five where there was no leakage. The rate of secondary adjacent and non-adjacent fractures is quite similar and there is no specific impact of intradiscal leakages on the occurrence of adjacent secondary fractures. Adjacent fractures occur sooner than distant secondary fractures. Sandwich fractures are associated with specific biomechanical conditions, with a 37.9% fracture rate in sandwich constellations.

Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited. OBJECTIVE: To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls. DESIGN/PATIENTS: Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group (n = 15) receiving 1 mg/m(2)/day GH or a non-GH-treated control group (n = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated. RESULTS: Infants in the GH group had a median age of 2.3 years [interquartile range (IQR) 1.7-3.0] and in the control group of 1.5 years (IQR 1.2-2.7) (P = 0.17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9.3% (-5.3 to 13.3) vs.-2.9% (-8.1 to 4.9) (P < 0.05) in mental development and +11.2% (-4.9 to 22.5) vs.-18.5% (-27.9 to 1.8) (P < 0.05) in motor development, respectively. CONCLUSION: One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.

[Randomized controlled trial on vessel sealing in thyroid surgery]. / Randomisierte kontrollierte Studie über die Gefässversiegelung in der Schilddrüsenchirurgie.

AIM: To compare conventional suture ligation with vessel sealing in thyroid surgery. METHODS: We investigated in a randomized controlled trial whether vessel sealing in thyroid surgery may shorten operative time compared to suture ligation. Included were all thyroid resections because of benign thyroid diseases. Primary endpoint was operative time and secondary endpoints were all postoperative complications. RESULTS: 150 patients were included into the study. 77 were randomized into the control group and 73 into the sealing group. Age, sex, BMI and extent of resection were not different between groups. Operative time was 10.2 min (CI - 1,3; 21,7) shorter in the sealing group. Sex, one- or two-sided resection, site of thyroid, and the experience of the surgeon had all a significant influence on operative time. Postoperative complications were not different between groups. CONCLUSION: Vessel sealing shortens operative time, especially if resection is performed by experienced surgeons, and did not increase postoperative complication rate.

Subcutaneous gentamycin implant to reduce wound infections after loop-ileostomy closure: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: After loop-ileostomy closure subcutaneous wound infection is the most frequent postoperative complication. Implantation of local antibiotics has been shown to reduce the incidence of wound infection after different surgical procedures, therefore, a subcutaneous application of a gentamycin implant may also decrease infection rate after ileostomy-closure. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the effectiveness of a subcutaneous gentamycin-collagen implant to reduce wound infection after loop-ileostomy closure. Patients had the same perioperative treatment and standardized anastomotic and closure technique. A collagen sponge with gentamycin was used in the treatment group and an identical collagen implant without antibiotics was used in the placebo group. RESULTS: Eighty patients (40 per group) were included. There was no difference between the groups with respect to demographics or in the postoperative course. The total wound infection rate was 10 percent with no difference between the gentamycin (n=4) and the collagen group (n=4) (P = 1.0). CONCLUSION: Subcutaneous implantation of a gentamycin sponge yields no clinically relevant reduction of the wound infection rate after loop-ileostomy closure so that routine use is not recommended in this procedure.