Relationship between Lipoprotein(a) and cardiovascular risk factors-data from 4602 participants of the ELITE study.

Lipoprotein(a) (Lp(a)) is becoming increasingly important as an independent risk factor for cardiovascular disease. Since no effective therapy currently exists other than lipid apheresis, the recommendation remains to optimally adjust all other cardiovascular risk factors (CVRF). In a Northwest German population study, the frequency of elevated Lp(a) levels and all other CVRF was investigated. The aim was to investigate whether individuals with elevated Lp(a) levels were also more likely to have other CVRFs. To date, 4602 individuals have been enrolled in the study, and blood pressure, weight, lipids, diabetes, medications, and pre-existing conditions were recorded in addition to Lp(a). In addition, questionnaires assessed physical activity, psychological stress, depression, and brain dysfunction. All participants received detailed individual recommendation about their CVRF and its treatment. In the further follow-up of 5 years, it will be examined how persons with elevated Lp(a) implemented these recommendations in comparison with participants without elevated Lp(a). The first group Lp(a) <75 nmol/L consisted of 3550 (80.2%), the Lp(a) 75-120 nmol/L group of 341 (7.4%) and the Lp(a) >120 nmol/L of 538 (11.7%). 81.6% of all participants had one or more CVRF. Age, sex, and prevalence of hypertension, diabetes, smoking, obesity, and exercise did not differ among the 3 groups. As expected, LDL-Cholesterol was significantly elevated in the Lp(a) >120 nmol/L group despite significantly more frequent use of statins. Significantly more often hypertensive patients were found in the Lp(a) >120 nmol/L group who were inadequately controlled by medication and significantly less often persons without further CVRF. No differences existed in the frequency of psychological stress, depression, and mild cognitive impairment. CVRF occur with comparable frequency in individuals with elevated Lp(a) levels. However, individuals with Lp(a) above 120 nmol/L were more likely to have poorly controlled blood pressure, elevated LDL-C, and less likely to have no other risk factors. This underlines that in case of Lp(a) elevation all further CVRF should be intensively adjusted, especially in case of strongly elevated values >120 nmol/L. However, these recommendations have not been adequately implemented in clinical care in this population to date.

Influence of individualized prevention recommendations after one year on the control of hypertension in 3,868 follow-up participants of the ELITE study.

OBJECTIVES: The ELITE study (German acronym for "Nutrition, lifestyle and individual information for prevention of heart attack, stroke and dementia") prospectively collects data on hypertension, cardiovascular risk factors (RF), dietary habits, physical activity, cognitive function, and quality of life in North-West Germany, which will then be improved through targeted individual information. The aim of the study is to improve the health of the participants in the long term and to identify reasons for a lack of implementation of prevention measures. METHODS: Of 4,602 included subjects, 3,868 could be studied so far at one-year follow-up. Blood pressure (BP) was measured according to the guidelines at admission and blood pressure history, premedication, sports behaviour and BMI were recorded by means of questionnaires and compared with the data collected in the follow-up examination after one year. RESULTS: The participants were evaluated in 4 groups (G): G1 - normotensive patients (n = 1,558), G2 - controlled hypertensive patients (n = 502), G3 - untreated uncontrolled hypertensive patients (n = 1,080), G4 - treated uncontrolled hypertensive patients (n = 728). In G1 blood pressure (RR) remained unchanged from 126.3/77.8 to 127.8/78.5, in G2 there was a significant (p < 0.001) RR increase from 128.1/77.0 to 134.9/79.8. In G3 and G4 RR decreased significantly (p < 0.001) from 149.9/90.0 to 143.5/86.9 and from 153.1/87.5 to 146.2 84.1 mmHg, respectively. In G3 and G4, RR decreased in 56.1% and 56.3% of subjects and increased in 18% and 21%, respectively. In contrast, RR increase was found more frequently in G1 and G2 (34.3% and 51%, respectively), and RR decrease less frequently (25.4 and 20.7%, respectively). The main reasons for RR decrease were weight loss, more exercise, and more antihypertensives. Frequently, improved compliance and dietary changes were given as reasons. As expected, the opposite often led to RR increase. CONCLUSION: 56% of the hypertensive participants succeeded in lowering their blood pressure, whereas there was a significant increase in blood pressure, especially in those who were well controlled with antihypertensives. This underlines the need to further motivate normotensive patients to maintain their normotension. The results show that the combination of individual written education and lifestyle interventions are an effective tool for the public health sector to combat hypertension. In our participants, lifestyle interventions have a significant impact on BP change. It should be noted critically that there are still too many patients who have not been reached.

Intrapartum Care Working Patterns of Midwives: The Long Road to Models of Care in Germany.

INTRODUCTION: Midwifery models of care help to enhance perinatal health outcomes, women's satisfaction, and continuity of care. Despite the ubiquitous presence of certified midwives at births in Germany, no research has investigated the diversity of midwives' practice patterns. Describing the variety of working patterns through which midwives provide intrapartum care may contribute to improving the organisation of midwifery services. METHODS: This cross-sectional survey took place in the region of Hannover and Hildesheim, Germany. Midwives attending births and practicing in hospitals and/or out-of-hospital were able to participate. Midwives who did not attend births were excluded. We assessed midwives' scope of services, practice locations, employment patterns, continuity of care, midwife-led births, and midwives' level of agreement with core values of midwifery care. The response rate of the survey was 32.7 % (69/211). RESULTS: We found that midwifery care services can be described according to midwives' employment patterns. The majority of midwives were employed in a hospital to provide intrapartum care (74.2 %, n = 49), and most also independently offered one or more antenatal and/or postpartum service/s. Only 25.8 % (n = 17) of midwives offered their services independently (laborist model of care). Independent midwives attended births in all three possible settings: hospital, free-standing birth centres and home. Significantly more independent midwives than employed midwives offered antenatal care and lactation consulting. Compared to employed midwives, significantly more independent midwives provided antenatal, intrapartum, and postpartum care to the same women, were more likely to know women before labour, and to offer one-to-one care during labour. DISCUSSION: The most common practice pattern among surveyed midwives was 'employment in a hospital' for provision of intrapartum care with additional postpartum and few antenatal services provided on an independent basis. Midwives who worked solely independently reported more continuity and one-to-one intrapartum care with women. Most midwives did not work in patterns that offered continuity of care or consistently provide one-to-one care. Future research should assess whether women in Germany desire more services similar to caseload midwifery.

[Outcomes of Planned Out-of-Hospital and Low-Risk Hospital Births in Lower Saxony]. / Outcomes geplanter außerklinischer und klinischer Low-Risk Geburten in Niedersachsen.

Introduction Internationally, there is debate on the safety of different birth settings inside and outside of hospitals. Low-risk women in Germany can choose where they give birth, and out-of-hospital births are especially necessary in regions lacking infrastructure. To date, national studies are required. Materials and Methods We investigated planned out-of-hospital (OH) and hospital births in Lower Saxony, Germany, in 2005. Women with a singleton fetus in the vertex position were included once they reached 34+0 gestational weeks. 1 273 out of 4 424 births were included via risk assessment. Outcomes were compared using Pearson's chi-squared test, the Mann-Whitney test, and logistic regression. Results 152 (36.6%) nulliparae (NP) and 263 (63.4%) multiparae (MP) gave birth out of hospital, 439 (51.2%) nulliparae and 419 (48.8%) multiparae in a hospital. 10.1% of women whose care started outside of the hospital needed a transfer to the hospital. Women who planned OH were older and had a higher level of education. Women without a migration background displayed an increased rate of out-of-hospital birth. A higher proportion received their antenatal care from midwives rather than medical doctors. Induction of labor was less likely for women with planned out-of-hospital births, as were other intrapartum interventions. In hospital births, fetal monitoring was more likely performed via cardiotocograph instead of intermittent auscultation. Duration of labor was significantly longer in OH births (median: NP: 9.01 h vs. 7.38 h; MP: 4.53 h vs. 4.25 h). Nulliparae had more spontaneous births out-of-hospital (94.7%) than in hospital (73.6%). There was no difference in adverse fetal outcomes, blood loss, and severe perineal lacerations. The perineum was less frequently intact in hospital births. Retained placenta was more often documented in out-of-hospital births. Conclusions In an out-of-hospital setting, fewer interventions were performed, spontaneous births occurred more often, and there was no difference in neonatal outcomes. OH birth appears reasonably safe with thorough pre-labor risk assessment and good transfer management. Some beneficial aspects of OH birth care (like continuity of care and restriction of routine interventions) could be adopted by hospital labor wards, leading to a higher rate of vaginal births and improved care.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

[Influence of the Corona pandemic on cardiovascular risk factors - Data from 1775 participants of the ELITE study before and during the Corona pandemic]. / Einfluss der Corona-Pandemie auf kardiovaskuläre Risikofaktoren ­ Daten von 1775 Teilnehmern der ELITE Studie vor und während der Corona Pandemie.

BACKGROUND: The COVID-19 pandemic and its interventions have led to a deficit in medical care and changes in people's lifestyles, which has consequently changed cardio- and cerebrovascular primary and secondary prevention. The existing data are mainly based on surveys. In addition to the problem of the accuracy of self-assessments, the pandemic per se and the massive public reporting may have biased the data.Only a few publications have compared data collected before the pandemic with results during the pandemic. The ELITE study has regularly monitored risk factors (RF) and psychosocial parameters (stress, depression, well-being, diet, brain performance, exercise) in over 5000 participants for years. From this study, data were analyzed from 1775 individuals collected before the onset and again during the pandemic (06/05/2020-25/01/2022). Thus, baseline values were unaffected by the pandemic. RESULTS: As expected, both improvements and worsening of the collected parameters were found. Blood pressure and depressive symptoms worsened significantly more often, with women more frequently affected. Weight and stress levels also increased more often than they improved. Only physical activity showed a slight increase. 24.1 % showed only deteriorations and no improvements in these parameters. In contrast, 19.6 % showed improvements exclusively. In the group with only worsening, there was a significant increase in individuals with the risk factors (RF) hypertension, obesity, elevated LDL cholesterol, nicotine, and diabetes mellitus. This resulted in an increase in individuals with 2 or more RF. In contrast, the number of individuals with 2 and more RF decreased in the group with only improvements. Strikingly, individuals with risk factors improved more frequently. CONCLUSION: A not insignificant part of the population experienced significant worsening of RF during the pandemic. This particularly affected blood pressure and depressive symptoms, and more often women.

Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis.

UNLABELLED: Fibrosis and steatosis are major histopathological alterations in chronic liver diseases. Despite various shortcomings, disease severity is generally determined by liver biopsy, emphasizing the need for simple noninvasive methods for assessing disease activity. Because hepatocyte cell death is considered a crucial pathogenic factor, we prospectively evaluated the utility of serum biomarkers of cell death to predict different stages of fibrosis and steatosis in 121 patients with chronic liver disease. We compared the M30 enzyme-linked immunosorbent assay (ELISA), which detects a caspase-cleaved cytokeratin-18 (CK-18) fragment and thereby apoptotic cell death, with the M65 ELISA, which detects both caspase-cleaved and uncleaved CK-18 and thereby overall cell death. Both biomarkers significantly discriminated patients with different fibrosis stages from healthy controls. However, whereas both markers differentiated low or moderate from advanced fibrosis, only the M65 antigen could discriminate even lower stages of fibrosis. The M65 assay also performed better in distinguishing low (≤10%) and higher (>10%) grades of steatosis. In a subgroup of patients, we evaluated the biomarkers for their power to predict nonalcoholic steatohepatitis (NASH). Importantly, both markers accurately differentiated healthy controls or simple steatosis from NASH. However, only serum levels of M65 antigen could differentiate simple steatosis from healthy controls. CONCLUSION: Cell death biomarkers are potentially useful to predict fibrosis, steatosis, or NASH. Compared with the widely used apoptosis marker M30, the M65 assay had a better diagnostic performance and even differentiated between lower fibrosis stages as well as between healthy individuals and patients with simple steatosis.

Apoptosis in extracorporeal preserved inguinal fat flaps of the rat.

Fat cells are fragile cells with a short life span outside the body. Ways to reduce cell death in a biochemical way are almost unknown due to scarce information on the type of cellular death that is induced in fat tissue. This study was designed to investigate the apoptotic pathways of fat tissue in a permanent perfusion bioreactor system with the Hannover preservation solution and the Eurocollins solution in fat flaps of rats. In Lewis rats, the inguinal adipofascial flaps were elevated bilaterally and placed in a bioreactor at 37°C. To detect caspases 3, 8, 9 and 12, immunofluorescence stains of fat tissue specimen were analysed at several time points after preservation of flaps were placed in Hannover solution and Eurocollins solution for 10 days. An additional visual assessment of viability by a calcein based life/dead test was performed. It revealed a superior viability of the adipose tissue preserved in Hannover solution. Immunofluorescence staining demonstrated that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors were activated, as Caspases 8, 9 and 12 were detected. Caspase 3 as an effector in the common apoptotic pathway was detected as well. Adipose tissue preserved at 37°C ex vivo in a bioreactor system undergoes apoptosis. Immunofluorescence examination of the fat tissue preserved ex vivo revealed that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors are being activated. Significantly less activation of Caspase 3, 8, 9 and 12 in flaps preserved in Hannover solution in comparison to Eurocollins was found, supporting the anti apoptotic characteristics of Hannover solution. Based on these findings, further research to modify the apoptotic pathways to ameliorate viability of fat tissue can be performed.

Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria.

Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from L-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In the present study, we investigated the status of the L-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC-MS/MS. The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase (DDAH) metabolite of ADMA, were measured by GC-MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with homocystinuria was significantly higher than in controls (660±158 vs. 475±77 nM, P=0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2±24.5 vs. 6.5±2.9 µmol/mmol creatinine, P=0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly lower ADMA plasma concentrations compared to controls (512±136 vs. 585±125 nM, P=0.009). Phenylketonuria patients and controls had similar L-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to healthy controls (1.7±1.7 vs. 0.7±1.2 µmol/mmol creatinine, P=0.003). Our study shows that the L-arginine/NO pathway is differently altered in children with phenylketonuria and homocystinuria. Analogous to hyperhomocysteinemic adults, elevated ADMA plasma concentrations could be a cardiovascular risk factor in children with homocystinuria. In phenylketonuria, the L-arginine/NO pathway seems not be altered. Delineation of the role of ADMA in childhood phenylketonuria and homocystinuria demands further investigation.

Increased asymmetric dimethylarginine (ADMA) dimethylaminohydrolase (DDAH) activity in childhood hypercholesterolemia type II.

Asymmetric dimethylarginine (ADMA) systemic concentrations are elevated in hypercholesterolemic adults and contribute to nitric oxide (NO) dependent endothelial dysfunction. Decreased activity of the key ADMA-hydrolyzing enzyme dimethylarginine dimethylaminohydrolase (DDAH) may be involved. Yet, the ADMA/DDAH/NO pathway has not been investigated in childhood hypercholesterolemia. We studied 64 children with hypercholesterolemia type II (HCh-II) and 54 normocholesterolemic (NCh) children (mean ± SD; age, years: 11.1 ± 3.5 vs. 11.9 ± 4.6). Plasma and urine ADMA was measured by GC-MS/MS. Dimethylamine (DMA), the ADMA metabolite, creatinine, nitrite and nitrate in urine were measured by GC-MS. The DMA/ADMA molar ratio in urine was calculated to estimate whole body DDAH activity. ADMA plasma concentration (mean ± SD; nM: 571 ± 85 vs. 542 ± 110, P = 0.17) and ADMA urinary excretion rate (mean ± SD: 7.1 ± 2 versus 7.2 ± 3 µmol/mmol creatinine, P = 0.6) were similar in HCh-II and NCh children. Both DMA excretion rate [median (25th-75th percentile): 56.3 (46.4-109.1) vs. 45.2 (22.2-65.5) µmol/mmol creatinine, P = 0.0004] and DMA/ADMA molar ratio [median (25th-75th percentile): 9.2 (6.0-16.3) vs. 5.4 (3.8-9.4), P = 0.0004] were slightly but statistically significantly increased in HCh-II children compared to NCh children. Plasma and urinary nitrite and nitrate were similar in both groups. In HCh-II whole body DDAH activity is elevated as compared to NCh. HCh-II children treated with drugs for hypercholesterolemia had lower plasma ADMA levels than untreated HCh-II or NCh children, presumably via increased DDAH activity. Differences between treated and untreated HCh-II children were not due to differences in age. In conclusion, HCh-II children do not have elevated ADMA plasma levels, largely due to an apparent increase in DDAH activity. While this would tend to limit development of endothelial dysfunction, it is not clear whether this might be medication-induced or represent a primary change in HCh-II children.

Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: description of the AFS-3D algorithm.

BACKGROUND: A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free-ß human chorionic gonadotropin (free-ß hCG) are placed into a three-dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called 'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to develop and test a new algorithm based on the results of previous studies. METHODS: A new static-sized sphere model was developed. Several scaling factors of the axes and the optional application of the modifications 'simulation' (SIM) and 'empty sphere positive' were tested on 15,227 data sets. An additional examination was performed on a second collective (n = 458). RESULTS: The application of the new AFS-3D model with static-sized spheres, a re-sampled ∆NT axis by a scaling factor of 0.125, and the application of SIM and Empty Box Positive resulted in a marked improvement of the test performance (area under curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second test collective. CONCLUSIONS: This novel approach is promising and should be tested on a larger, independent collective.

Cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs.

OBJECTIVE: To determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs. STUDY DESIGN: Prospective, randomized, experimental crossover study. ANIMALS: Five adult healthy Beagle dogs (one male and four females, weighing 12.8-16.4 kg). METHODS: Dogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg(-1) acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg(-1) L-methadone/ 0.025 mg kg(-1) fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant. RESULTS: Baseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes.

The granulation tissue preservation technique in regenerative periodontal surgery-a randomized controlled clinical trial.

OBJECTIVES: To investigate if the application of the granulation tissue preservation technique (GTPT) in regenerative therapy of infrabony periodontal defects results in more clinical attachment level (CAL) gain and more radiographic bone gain (RBG) than the conventional resective approach 12 months after surgery. MATERIALS AND METHODS: Forty patients exhibiting at least one infrabony defect with a probing pocket depth (PPD) ≥6 mm and a radiographic infrabony component (INFRAX-ray ) ≥3 mm were randomly treated with the GTPT (test group) or the double-flap approach with resection of the defect-filling granulation tissue (control group). Enamel matrix derivatives were applied in both groups. Clinical and radiographic parameters were recorded at baseline (t0), 6 months (t1), and 12 months (t2) after surgery. The primary outcome variable was CAL gain between t0 and t2. RESULTS: When all patients were considered, ΔCALt0-t2 did not differ significantly between the two groups (p = .160). Significant PPD reduction (test group: 4.38 ± 1.36 mm; control group: 4.06 ± 2.38 mm), CAL gain (test group: 3.75 ± 1.24 mm; control group: 2.88 ± 2.09 mm), and RBG (test group: 3.06 ± 1.74 mm; control group: 3.27 ± 2.19 mm) were achieved at t2 in both groups. Using multivariate linear regression, PPDt0 and group were identified as variables with the greatest influence on ΔCALt0-t2 . PPDt0 and INFRAX-ray were identified as variables with the greatest influence on RBGt0-t2 . Patients with a defect angle >22° showed significantly more CAL gain in the test group (t0-t1: 3.08 ± 1.38 mm; t0-t2: 3.62 ± 0.96 mm) than in the control group (t0-t1: 1.77 ± 1.54 mm; t0-t2: 2.18 ± 1.83 mm). CONCLUSIONS: Regarding all patients, the study failed to show significant differences between the test and control groups. However, the GTPT appears to lead to more CAL gain in noncontaining infrabony defects.

Regular Exercise is Associated with a More Favorable Cardiovascular Risk Profile, Better Quality of Life, Less Depression and Less Psychological Stress.

INTRODUCTION: It is well documented that insufficient physical activity (PA) contributes substantially to cardiovascular diseases. The number of physically active people in Germany is still too low. METHODS: In ELITE study in Germany, 4602 participants are regularly examined for cardiovascular risk factors (CVRF). The aim is to motivate participants to improve their CVRF through individual recommendations and regular follow-up. Here, the PA data are presented in correlation with CVRF at baseline. A feature of this presentation is that the usual CVRF but also the effects on psychosocial factors were recorded simultaneously. RESULTS: Participants were divided into 3 groups based on their PA: 1. frequent exercise (FE): daily to 2-3x per week (41.4%), 2. moderate exercise (ME): 1x/week to 2x/month (28.8%), 3. rarely exercise (RE): 1x/month to not at all (29.8%). Age did not differ in the 3 groups. The most common CVRF was arterial hypertension, which decreased significantly with an increase in PA. Diabetes, nicotine, and increased BMI were also significantly less frequent in group 1. Antihypertensives were taken less frequently in this group 1. Less physically active participants were significantly more likely to have 3 or more additional CVRF. While group 1 consumed more fruit (64%) and considerably less pork, in group 2 and 3 only 58.3% and 50.3% respectively included fruit in their diet. FE also had a favorable effect on stress, depression and general well-being, all of which were significantly better in group 1. CONCLUSION: Results confirm the beneficial influences of exercise on known CVRF and on psychosocial parameters. The prevalence of several CVRF per person at low levels of sport is of particular concern, as these participants would benefit most. During a 5-year follow-up, participants will receive intensive education on the need to increase PA. It remains to be seen how successful the effort will be.

Energy metabolism in umbilical endothelial cells from preterm and term neonates.

AIM: The aim of this study was to investigate the impact of gestational age on energy metabolism in human umbilical vein endothelial cells (HUVECs) of preterm and term neonates. METHODS: Activities of respiratory chain (RC) complexes I-V, citrate synthase (CS), overall mitochondrial fatty acid oxidation (FAO), carnitine palmitoyltransferase 2 (CPT2), glycolytic enzymes as well as energy-rich phosphates in HUVECs from uncomplicated term and preterm pregnancies were measured. Neonatal acylcarnitine profiles were analyzed postpartum. RESULTS: Activities of RC complexes II+III, IV, V, and CS were higher in HUVECs from immature pregnancies. Overall FAO did not change, whereas CPT2 activity was higher in term neonates. RC complexes II-V and CS correlated inversely to gestational age, as well as CPT2 activity within the term cohort. Phosphofructokinase activity increased with maturation; lactate dehydrogenase and hexokinase as well as energy-rich phosphates remained constant. In blood, long-chain acylcarnitines were higher in term neonates. CONCLUSIONS: Gestational age-dependent differences of energy-providing pathways in HUVECs were shown. Alterations of RC complexes with gestational age may be an adaptive process to cope with metabolic stress during birth; reduced oxidative phosphorylation and high glycolytic activity make HUVECs less susceptible to peripartum hypoxic damage. We hypothesize that HUVECs of premature neonates are metabolically maladapted to birth, which may be responsible for perinatal complications.

Is there an association between comorbidities and the outcome of microvascular free tissue transfer?

The aim of this study was to evaluate the relevant conditions for safe free flap transfers. The authors retrospectively studied the data from 150 patients who received free flaps at a single institution. Many parameters were analyzed to reveal if there was a correlation with respect to surgical or medical complications. Regarding safety of free tissue transfer, we found a worse prognosis in flaps where a revision of the microanastomosis had to be performed. Platelet count and leukocyte count had an impact on the prognosis. Patients older than 60 years did not have an increased rate of surgical complications. Apart from active osteomyelitis, the presence of comorbid conditions did not significantly impair the outcome of flap transfer, although smoking and diabetes correlated with minor surgical complications like wound breakdown or hematoma, respectively. Besides one case of lethal heart failure of an octogenarian patient, no severe medical complications occurred in this series of patients. Microvascular free tissue transfer is not significantly impaired by age and most comorbidities. Osteomyelitis as well as elevated leukocytes and lowered platelets may increase the complication rate and worsen the surgical prognosis. Smoking and diabetes might prolong the hospital course of the patients.

Football beats hypertension: results of the 3F (Fit&Fun with Football) study.

OBJECTIVES: Football as the most popular sport could improve insufficient physical activity in patients with cardiovascular risk factors. A modified 'healthy' football training format could motivate hypertensive patients to return to sport and improve risk factors. METHODS: The 3F study: 'Fit and Fun with Football' a prospective interventional study with 1 year follow-up. Football group: n = 103, structured 'health'-football training (1×/week, 90 min) led by Deutscher Fußball Bund-licensed football coaches. Hypertensive patients at least 45 years who have not exercised for several years were compared with a control group (n = 105). PRIMARY STUDY OBJECTIVE: Reduction of office (OBP) and/or 24-h ambulatory blood pressure (BP) monitoring (ABPM) and/or reduction of number or dosage of antihypertensive medication. MAIN RESULTS: OBP values decreased significantly in the football group from 142.6/87.9 to 130.8/81.8 mmHg (P < 0.001), in the control group the values increased slightly (NS). ABPM values decreased significantly in the football group, while a slight increase was found in the control group. At the end of the study, the mean values in the football group of both OPB (P < 0.001) and ABPM (systolic P < 0.001, diastolic P = 0.017) were significantly lower than in the control group. Significantly more people in the football group were able to reduce antihypertensive patients than in the control group (football group:16, control group:6), while more participants in the control group intensified antihypertensive therapy (football group:3, control group:14) (P < 0.001). Among the secondary endpoints, there was a weight loss of 3 kg in the football group and an increase of 1.7 kg in the control group (P < 0.001). CONCLUSION: Offering modified 'healthy' football-training to middle-aged hypertensive patients can lead to better BP control and a reduction of antihypertensive medication. Therefore, the offer of 'health football' should be established and supported by clubs, insurances and authorities.

Partial rescue of the KIT-deficient testicular phenotype in KitW-v/KitW-v Tg(TSPY) mice.

TSPY encodes the testis-specific protein Y-linked. In man, expression of TSPY is restricted to the testis, where TSPY is expressed in spermatogonia, primary spermatocytes, and round spermatids, and to the prostate gland. There is circumstantial evidence that TSPY is involved in spermatogonial proliferation and gonadal tumorigenesis. Because the laboratory mouse carries the Tspy gene in a naturally silenced state (Tspy-ps), we previously restored TSPY activity in mice and generated a TSPY transgenic mouse line in which the organization and expression of the human TSPY transgene follow the human pattern. In the present study, we generated TSPY transgenic KIT-deficient Kit(W-v)/Kit(W-v) mice and analyzed the histology of the testes and epididymides in order to contribute to understanding TSPY function in early germ cell development and spermatogenesis. The KIT receptor and its ligand KITL, previously called stem cell factor, have an indispensable role in hematopoiesis, melanogenesis, and gametogenesis. Homozygous Kit(W-v) mutant male mice on a C57BL/6J background with a mutation in the Kit gene are infertile due to an almost total loss of germ cells in the testes. In this study, histological analyses of testes and epididymides showed an increased number of meiotic and postmeiotic germ cells in Kit(W-v)/Kit(W-v) Tg(TSPY) mice compared with age-matched Kit(W-v)/Kit(W-v) controls. TSPY was able to restore fertility of some but not all TSPY transgenic Kit(W-v)/Kit(W-v) males. Our findings show that TSPY is able to partially rescue spermatogenesis and fertility of Kit(W-v)/Kit(W-v) mutants and thereby point to a putative role of TSPY in fetal and adult germ cell proliferation.

Quality assured ultrasound simulator training for the detection of fetal malformations.

OBJECTIVE: Sonographic training in obstetrics differs broadly in Germany, although there are clearly defined quality-oriented requirements. In order to improve professional education, a training concept was devised utilizing an ultrasound simulator system. DESIGN: Between October 2004 and May 2006, 100 obstetric ultrasound training courses were held in 12 federal states of Germany. In these daily courses, doctors were trained in the detection of the most common malformations. SAMPLE: One hundred training courses with a total of 1,266 participants. METHODS: As a measure of quality assurance, a standardized questionnaire focusing on testing sonographic proficiency before and after the courses was issued in order to analyze the effect of these simulator-based ultrasound courses. MAIN OUTCOME MEASURES: Effectiveness of the method with reference to its potential role in structured sonographic training. RESULTS: The concept found prevailing approval (90%) at the level of principle, practical implementation, and clinical usefulness. Of the participants, 91% estimated their subjective training effect as good. The questionnaire analysis showed significant improvement. On average, 75.3% of the questions relating to sonographic proficiency were answered correctly at the end of the course as opposed to 48.6% at the beginning. CONCLUSION: Structured ultrasound training courses based on an ultrasound simulator system seem to be useful for defining a basic standardized quality of training and significantly improving examiners' skills. This is a suitable additional instrument to improve the education in obstetric ultrasound.

[Comparison of current methods of prenatal screening for down syndrome]. / Comparación de los métodos actuales de cribado prenatal del síndrome de down.

BACKGROUND: In Spain all pregnant women aged 35 years and older are offered genetic examination through invasive testing in order to detect fetal trisomy 21 cases (maternal age indication (MAI)). In the last decade five distinct software programs utilizing the "first trimester screening (FTS)" were developed. The objective of this study is to compare the test performance of the different screening methods in order to detect the best current approach. METHODS: 7.736 complete first trimester screenings, including the fetal outcome, were realized between 31.08.1999 and 24.05.2007 in three prenatal health centres in Hannover, Peine, and Wolfenbüttel in Germany. Out of these 6.508 cases were analyzed retrospectively in this study. Maternal age was determined and risk calculation with the software programs PIA, PRC, JOY, AFS and AFS-3D was executed. RESULTS: The MAI reached a sensitivity of 57.50%, detecting only 23 out of 40 trisomy 21 cases, and a false positive rate of 21.60%. In comparison, all risk calculation programs obtained superior results, attaining a sensitivity between 90.00% (AFS) and 92.50% (PIA, PRC, JOY, AFS-3D) and a false positive rate between 2.64% (AFS-3D) and 7.87% (PIA). The difference was highly significant (p<0.0001) CONCLUSIONS: The MAI is obsolete and inadequate in comparison with the risk calculation software, out of which all obtained test performances within the range of comparable international publications. Among these programs, JOY, AFS, and AFS-3D obtained the best results.