Effects of 66 years of water management and hydroclimatic change on the urban hydrology and water quality of the Panke catchment, Berlin, Germany.

Long-term records of combined stream flow and water chemistry can be an invaluable source of information on changes in the quantity and quality of water resources. To understand the effect of hydroclimate and water management on the heavily urbanized Panke catchment in Berlin, Germany, an extensive search, collation and digitization of historic data from various sources was undertaken. This integrated a unique 66-year spatially distributed record of stream water quality, a 21-year record of groundwater quality and a 31-year stream flow record. These data were analysed in the context of hydroclimatic variability, as well as the history and technological evolution of water resource management in the catchment. To contextualize the effect of droughts, "average" and wet years the Standard Precipitation Index (SPI) was applied. As upstream sites have been less regulated by human impacts, the flow regime is most sensitive to changes in hydroclimatic conditions, while downstream sites are more influenced by wastewater effluents, urban storm drains and inter-basin transfers for flood alleviation. However, at all sites, a general increase in maximum event discharge was observed until a recent drought, starting in 2018. In general, water quality in the catchment has gradually improved as a result of management change and increasingly effective wastewater treatment, though in some places legacy and/or contemporary urban and rural groundwater contamination may be affecting the stream. Hydroclimatic changes, particularly drought years can affect water quality classes, and alter the chemostatic/dynamic behaviour of catchment export patterns. These insights from the Panke catchment underline the importance of strategic adaptation and improvement of water treatment and water resource management in order to enhance the quality of urban water courses. It also demonstrates the importance of long-term integrated data sets.

Liver segmental volume and attenuation ratio (LSVAR) on portal venous CT scans improves the detection of clinically significant liver fibrosis compared to liver segmental volume ratio (LSVR).

BACKGROUND: The aim of this proof-of-concept study was to show that the liver segmental volume and attenuation ratio (LSVAR) improves the detection of significant liver fibrosis on portal venous CT scans by adding the liver vein to cava attenuation (LVCA) to the liver segmental volume ratio (LSVR). MATERIAL AND METHODS: Patients who underwent portal venous phase abdominal CT scans and MR elastography (reference standard) within 3 months between 02/2016 and 05/2017 were included. The LSVAR was calculated on portal venous CT scans as LSVR*LVCA, while the LSVR represented the volume ratio between Couinaud segments I-III and IV-VIII, and the LVCA represented the density of the liver veins compared to the density in the vena cava. The LSVAR and LSVR were compared between patients with and without significantly elevated liver stiffness (based on a cutoff value of 3.5 kPa) using the Mann-Whitney U test and ROC curve analysis. RESULTS: The LSVR and LSVAR allowed significant differentiation between patients with (n = 19) and without (n = 122) significantly elevated liver stiffness (p < 0.001). However, the LSVAR showed a higher area under the curve (AUC = 0.96) than the LSVR (AUC = 0.74). The optimal cutoff value was 0.34 for the LSVR, which detected clinically increased liver stiffness with a sensitivity of 53% and a specificity of 88%. With a cutoff value of 0.67 for the LSVAR, the sensitivity increased to 95% while maintaining a specificity of 89%. CONCLUSION: The LSVAR improves the detection of significant liver fibrosis on portal venous CT scans compared to the LSVR.

Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.

Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs.

Liver MR relaxometry at 3T - segmental normal T1 and T2* values in patients without focal or diffuse liver disease and in patients with increased liver fat and elevated liver stiffness.

Magnetic resonance (MR) T1 and T2* mapping allows quantification of liver relaxation times for non-invasive characterization of diffuse liver disease. We hypothesized that liver relaxation times are not only influenced by liver fibrosis, inflammation and fat, but also by air in liver segments adjacent to the lung - especially in MR imaging at 3T. A total of 161 study participants were recruited, while 6 patients had to be excluded due to claustrophobia or technically uninterpretable MR elastography. Resulting study population consisted of 12 healthy volunteers and 143 patients who prospectively underwent multiparametric MR imaging at 3T. Of those 143 patients, 79 had normal liver stiffness in MR elastography (shear modulus <2.8 kPa, indicating absence of fibrosis) and normal proton density fat fraction (PDFF < 10%, indicating absence of steatosis), defined as reference population. T1 relaxation times in these patients were significantly shorter in liver segments adjacent to the lung than in those not adjacent to the lung (p < 0.001, mean of differences 33 ms). In liver segments not adjacent to the lung, T1 allowed to differentiate significantly between the reference population and patients with steatosis and/or fibrosis (p ≤ 0.011), while there was no significant difference of T1 between the reference population and healthy volunteers. In conclusion, we propose to measure T1 relaxation times in liver segments not adjacent to the lung. Otherwise, we recommend taking into account slightly shorter T1 values in liver segments adjacent to the lung.

Impact of performance in a mandatory postgraduate surgical examination on selection into specialty training.

BACKGROUND: The Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination is undertaken by large numbers of trainees in the UK and internationally as a mandatory step within surgical training. Unlike some high-stakes medical examinations, the MRCS is yet to be validated. A quantitative study was undertaken to assess its predictive validity by investigating the relationship between MRCS (Parts A and B) and national selection interview scores for general and vascular surgery in the UK. METHODS: Pearson correlation coefficients were used to examine the linear relationship between each assessment, and linear regression analyses were employed to identify potential independent predictors of the national selection score. All UK medical graduates who attempted the interview in 2011-2015 were included. RESULTS: Some 84·4 per cent of the candidates (1231 of 1458) were matched with MRCS data. There was a significant positive correlation between the first attempt score at Part B of the MRCS examination and the national selection score (r = 0·38, P < 0·001). In multivariable analysis, 17 per cent of variance in the national selection first attempt score was explained by the Part B MRCS score and number of attempts (change in R 2 value of 0·10 and 0·07 respectively; P < 0·001). Candidates who required more than two attempts at Part B were predicted to score 8·1 per cent less than equally matched candidates who passed at their first attempt. CONCLUSION: This study supports validity of the MRCS examination, and indicates its predictive value regarding entry into specialist training.

Epicardial Fat Volume and Aortic Stiffness in Healthy Individuals: A Quantitative Cardiac Magnetic Resonance Study.

PURPOSE: To determine epicardial fat volume (EFV) and aortic stiffness (assessed by aortic pulse wave velocity (PWV)) in healthy individuals, and to investigate the relationship of these parameters, and their association with body mass index (BMI) and age. MATERIALS AND METHODS: 58 subjects (29 men, mean age 44.7 ± 13.9 years[y]) underwent a CMR exam at 1.5 Tesla. A 2 D velocity-encoded CMR scan was acquired to determine PWV. The EFV was measured based on a 3 D-mDixon sequence. Group comparisons were made between younger (age < 45y; n = 30; mean age 33.4 ±â€Š6.6y) and older (> 45y; n = 28; 56.7 ± 8.4y) subjects and between subjects with a BMI < 25 kg/m(2) (n = 28; BMI 21.9 ±â€Š2.5 kg/m(2)) and a BMI > 25 kg/m(2) (n = 30; 28.7 ±â€Š4.0 kg/m(2)). Associations between the determined parameters were assessed by analyses of covariance (ANCOVAs). RESULTS: The mean values of PWV and EFV (normalized to body surface area) were 6.9 ±â€Š1.9 m/s and 44.2 ±â€Š25.0 ml/m(2), respectively. The PWV and EFV were significantly higher in the older group (PWV = 7.9 ±â€Š2.0 m/s vs. 6.0 ±â€Š1.2 m/s; EFV = 54.7 ml/m² vs. 34.5 ml/m²; p < 0.01, each), with no significant differences in BMI or sex. In the overweighted group the EFV was significantly higher than in subjects with a BMI < 25 kg/m² (EFV = 56.1 ±â€Š27.1 ml/m(2) vs. 31.5 ±â€Š14.6 ml/m(2); p < 0.01) but without a significant difference in PWV. ANCOVA revealed a significant correlation between EFV and PWV, also after adjustment for age (p = 0.025). CONCLUSION: An association was found between age and EFV as well as PWV. EFV and PWV were related to each other also after adjustment for age. The metabolic and pro-inflammatory activity found with increased epicardial fat volume may promote the development of atherosclerosis and aortic stiffness. CMR may be valuable for future studies investigating the relationship between EFV and PWV in patients with increased cardiovascular risk. KEY POINTS: • EFV and PWV can be assessed in a single CMR exam.• EFV and aortic stiffness are both associated with cardiovascular risk.• EFV correlates with aortic stiffness, possibly due to similar pro-inflammatory mechanisms. Citation Format: • Homsi R, Thomas D, Gieseke J et al. Epicardial Fat Volume and Aortic Stiffness in Healthy Individuals: A Quantitative Cardiac Magnetic Resonance Study. Fortschr Röntgenstr 2016; 188: 853 - 858.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Worksite nutrition supports and sugar-sweetened beverage consumption.

OBJECTIVE: This study examined the link between worksite environmental supports for nutrition behaviours and sugar-sweetened beverage (SSB) consumption and offers insight into potential intervention points for reducing SSB consumption and combatting overweight and obesity. METHODS: Perceived worksite supports for healthy nutrition and self-reported SSB consumption were analysed for 2,015 working adults in the state of Missouri using a subset of questions from the Supports at Home and Work for Maintaining Energy Balance (SHOW-ME) study. RESULTS: Employees' use of vending facilities and the availability of water coolers/water bottles was significantly associated with increased SSB consumption, while use of cafeterias was significantly associated with decreased SSB consumption. Symbols or signs to identify healthy alternatives were significantly associated with sports drink consumption. CONCLUSIONS: This study supports previous work indicating the worksite as a necessary environment for nutrition interventions. When choices (vending and cafeteria) are provided, employees report making healthier decisions. For worksites without cafeterias, alternatives should be explored including mobile food trucks and farmer's markets.

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.

Do surgical trainees believe they are adequately trained to manage the ageing population? A UK survey of knowledge and beliefs in surgical trainees.

OBJECTIVE: Increasing numbers of older patients are undergoing surgery. Older surgical patients are at a higher risk of perioperative complications and mortality. Multimorbidity, frailty, and physiological changes of ageing contribute to adverse outcomes. These complications are predominantly medical, rather than directly surgical. Guidelines recommend preoperative assessment of comorbidity, disability, and frailty in older patients undergoing surgery and closer perioperative collaboration between surgeons and geriatricians. We conducted a survey to assess knowledge and beliefs of surgical trainees toward common perioperative problems encountered in older surgical patients. DESIGN: Paper-based survey. SETTING: Unselected UK surgical training-grade physicians (CT1-ST8) attending the 2013 Congress of The Association of Surgeons of Great Britain and Ireland, Glasgow, UK, May 1-3, 2013. PARTICIPANTS: A total of 160 eligible UK surgical trainees attending the conference were invited to participate in the survey. Of them, 157 participated. RESULTS: Of the trainees, 68% (n = 107) reported inadequate training and 89.2% (n = 140) supported the inclusion of geriatric medicine issues in surgical curricula. Of the respondents, 77.2% (n = 122) were unable to correctly identify the key features required to demonstrate mental capacity, and only 3 of 157 respondents were familiar with the diagnostic criteria for delirium. Support from geriatric medicine was deemed necessary (84.7%, n = 133) but often inadequate (68.2%, n = 107). Surgical trainees support closer collaboration with geriatric medicine and shared care of complex, older patients (93.6%, n = 147). CONCLUSIONS: UK surgical trainees believe that they receive inadequate training in the perioperative management of complex, older surgical patients and are inadequately supported by geriatric medicine physicians. In this survey sample, trainee knowledge of geriatric issues such as delirium and mental capacity was poor. Surgical trainees support the concept of closer liaison and shared care of complex, older patients with geriatric medicine physicians. Changes to surgical training and service development are needed.

Decreasing sound and vibration during ground transport of infants with very low birth weight.

OBJECTIVE: To measure the effectiveness of modifications to reduce sound and vibration during interhospital ground transport of a simulated infant with very low birth weight (VLBW) and a gestational age of 30 weeks, a period of high susceptibility to germinal matrix and intraventricular hemorrhage. STUDY DESIGN: Researchers measured vibration and sound levels during infant transport, and compared levels after modifications to the transport incubator mattresses, addition of vibration isolators under incubator wheels, addition of mass to the incubator mattress and addition of incubator acoustic cover. RESULT: Modifications did not decrease sound levels inside the transport incubator during transport. The combination of a gel mattress over an air chambered mattress was effective in decreasing vibration levels for the 1368 g simulated infant. CONCLUSION: Transport mattress effectiveness in decreasing vibration is influenced by infant weight. Modifications that decrease vibration for infants weighing 2000 g are not effective for infants with VLBW. Sound levels are not affected by incubator covers, suggesting that sound is transmitted into the incubator as a low-frequency vibration through the incubator's contact with the ambulance. Medical transportation can apply industrial methods of vibration and sound control to protect infants with VLBW from excessive physical strain of transport during vulnerable periods of development.

Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The DELTA Study).

AIMS: Examine the association between weight loss and adherence with glycaemic goal attainment in patients with inadequately controlled T2DM. MATERIALS AND METHODS: Patients ≥ 18 years with T2DM from a US integrated health system starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index date) with baseline HbA1c ≥ 7.0% were included in this cohort study. Target HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and ≥ 3% loss in body weight. Patient-reported medication adherence was assessed per the Medication Adherence Reporting Scale. Structural equation modelling was used to describe simultaneous associations between adherence, weight loss and HbA1c goal attainment. RESULTS: Inclusion criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naïve; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index diabetes medication. At 6 months mean weight change was -1.3 (5.1) kg (p = 0.39); 28.1% had weight loss of ≥ 3%. Mean HbA1c change was -1.2% (1.8) (p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and diabetes therapies that lead to weight loss (metformin, GLP-1) were associated with weight loss ≥ 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment. CONCLUSIONS: Weight loss ≥ 3% and medication adherence were associated with HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal attainment than medication adherence in this study population. It is important to consider weight-effect properties, in addition to patient-centric adherence counselling, when prescribing diabetes therapy.

High temporal and high spatial resolution MR angiography (4D-MRA).

In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high field strengths (and thus potentially better signal-to-noise ratios) were developed. At the same time, parallel imaging and "echo-sharing" techniques were refined to allow for increasingly high spatial and temporal resolution in dynamic magnetic resonance angiography ("time-resolved" = TR-MRA). This technological progress facilitated tracking the passage of intra-venously administered contrast agent boluses as well as the acquisition of volume data sets at high image refresh rates ("4D-MRA"). This opened doors for many new applications in non-invasive vascular imaging, including simultaneous anatomic and functional analysis of many vascular pathologies including arterio-venous malformations. Different methods were established to acquire 4D-MRA using various strategies to acquire k-space trajectories over time in order to optimize imaging according to clinical needs. These include "keyhole"-based techniques (e. g. 4D-TRAK), TRICKS - both with and without projection - and HYPR-reconstruction, TREAT, and TWIST. Some of these techniques were first introduced in the 1980 s and 1990 s, were later enhanced and modified, and finally implemented in the products of major vendors. In the last decade, a large number of studies on the clinical applications of TR-MRA was published. This manuscript provides an overview of the development of TR-MRA methods and the 4D-MRA techniques as they are currently used in the diagnosis, treatment and follow-up of vascular diseases in various parts of the body.

p53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors.

BACKGROUND: Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDACi-induced effects has not been fully elucidated. We investigated the anticancer effects of four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in p53 status. METHODS: Effects were assessed by MTT assay, flow-cytometric analyses of propidium iodide uptake, mitochondrial depolarisation and cell-cycle distribution, as well as by gene expression profiling. RESULTS: Vorinostat was equally effective in p53 wild-type and null cells, whereas entinostat was less effective in p53 null cells. Histone deacetylase inhibitors treatment suppressed the expression of MDM2 and increased the abundance of p53. Combination treatments showed that vorinostat enhanced the cytotoxic activity of TRAIL and bortezomib, independent of the cellular p53 status. Investigations into the effects of an inhibitor of the sirtuin class of HDAC, tenovin-1, revealed that tenovin-1-mediated cell death hinged on p53. CONCLUSION: These results demonstrate that vorinostat activates p53, but does not require p53 for inducing its anticancer action. Yet they also demonstrate that entinostat-induced cytotoxic effects partially depend on p53, indicating that different HDACi have a different requirement for p53.

Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients.

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.

[Arterial hypertension: guideline acceptance and implementation in workaday life of internists and general practitioners in Thuringia]. / Arterielle Hypertonie: Leitlinienakzeptanz und -implementierung im Thüringer Praxisalltag von Internisten und Allgemeinmedizinern.

BACKGROUND AND OBJECTIVE: Although evidence-based medical guidelines are widely accepted it is not clear how they are implemented in daily clinical work. The aim of this study was a Thuringia-wide analysis of hypertension diagnosis and treatment in clinical practice of internists and general practitioners, combined with the evaluation of guideline implementation. METHODS: 1884 Thuringian internists and general practitioners were interviewed using a postally delivered, validated questionnaire to assess knowledge and implementation of the hypertension guidelines. RESULTS: 33,4 % of the physicians participated in our survey (433 general practitioners, 197 internists). 98 % of the participants routinely treat hypertension. Internists reported significantly more frequently to treat patients with resistance to antihypertensive therapy. Compared with older physicians and general practitioners, internists were significantly more likely to initiate diagnostic procedures for secondary hypertension according to the guidelines. Long-term measurement of arterial blood pressure in patients with more than three antihypertensive drugs and in cases of suspected endorgan damage or sleep apnea syndrome was more frequently applied by internists. 82,1 % of the participants reported to prescribe nonpharmacological therapies because of their efficacy. ACE-inhibitors (41,6 %) and beta-blockers (34,6 %) were preferred for monotherapy of hypertension without risk factors. ACE-inhibitors (80,1 %), followed by angiotensin receptor antagonists (12,1 %), were primarily selected in hypertensive patients with diabetic nephropathy. In left-ventricular hypertrophy, ACE inhibitors were favoured, too (67%). CONCLUSION: This survey indicates that in clinical practice doctors treat hypertensives according to official guidelines. However, there is a need for further education especially regarding indication of long-term measurement of arterial blood pressure. Continued education related to diagnosis and treatment of arterial hypertension and implementation of guidelines remains a permanent challenge for doctors.

Ultrasonographical and histological cross-sectional study of the human superficial branch of the radial nerve.

PURPOSE: The superficial branch of radial nerve (SBRN) is one of the cutaneous nevus biopsied for diagnosis of peripheral neuropathy. The purpose of this study is to find out the cross sectional microanatomy of the (SBRN) at antecubital fossa for changes in the fascicular, non-fascicular components with respect to age and also to find cross sectional area of SBRN in healthy volunteers. MATERIALS AND METHODS: Sixty SBRN were harvested bilaterally from 30 fresh human bodies (25 males and five females) with ages of 37 to 88 years. Samples were divided into three age groups (G1, 37-55 years; G2, 55-70 years; G3, ≥ 71 years) and studied at different magnifications after histological processing for morphometric analysis - total cross-sectional (Asc), fascicular (Af), and non-fascicular area (Anonf). Fifteen volunteers SBRN cross sectional area was measured by ultrasonography (US). RESULTS: The SBRN was found to have 2-6 fascicles. The differences in the adipose tissue (FAT) areas, between G1 and G2 (p=0.233) and between G2 and G3 (p=0.458) were not statistically significant. However, a significant difference was seen between G3 and G1 (p=0.021). The differences in the non-adipose tissue (FAT) areas, between G1 and G2 (p=0.110), between G2 and G3 (p=0.950) and between G3 and G1 (p=0.210) were not statistically significant. The amount of adipose tissue (FAT) in the epifascicular and interfascicular region increased in elderly individuals (age ≥ 71 years). Ultrasonographic cross-sectional area ranged from 2 to 3 mm². CONCLUSIONS: Our study revealed comparatively more adipose tissue in human SBRN with advanced age (≥ 71 years). Findings may help to explain poor prognosis with advancing age following repair. SBRN ultrasonographical Asc was comparable to histological Asc in ages between 37-55 years.

Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence.

Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). Additional evidence consistent with a therapeutic role for pregnenolone in schizophrenia includes neurosteroid changes following administration of certain antipsychotics in rodent models. For example, clozapine elevates pregnenolone levels in rat hippocampus, and these increases may potentially contribute to its superior antipsychotic efficacy [Marx et al. (2006a) Pharmacol Biochem Behav 84:598-608]. Further, pregnenolone levels appear to be altered in postmortem brain tissue from patients with schizophrenia compared to control subjects [Marx et al. (2006c) Neuropsychopharmacology 31:1249-1263], suggesting that neurosteroid changes may play a role in the neurobiology of this disorder and/or its treatment. Although clinical trial data utilizing pregnenolone as a therapeutic agent in schizophrenia are currently limited, initial findings are encouraging. Treatment with adjunctive pregnenolone significantly decreased negative symptoms in patients with schizophrenia or schizoaffective disorder in a pilot proof-of-concept randomized controlled trial, and elevations in pregnenolone and allopregnanolone post-treatment with this intervention were correlated with cognitive improvements [Marx et al. (2009) Neuropsychopharmacology 34:1885-1903]. Another pilot randomized controlled trial recently presented at a scientific meeting demonstrated significant improvements in negative symptoms, verbal memory, and attention following treatment with adjunctive pregnenolone, in addition to enduring effects in a small subset of patients receiving pregnenolone longer-term [Savitz (2010) Society of Biological Psychiatry Annual Meeting New Orleans, LA]. A third pilot clinical trial reported significantly decreased positive symptoms and extrapyramidal side effects following adjunctive pregnenolone, in addition to increased attention and working memory performance [Ritsner et al. (2010) J Clin Psychiatry 71:1351-1362]. Future efforts in larger cohorts will be required to investigate pregnenolone as a possible therapeutic candidate in schizophrenia, but early efforts are promising and merit further investigation. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Distribution of sympathetic fiber areas in the sensory nerves of forearm: an immunohistochemical study in cadavers.

PURPOSE: Secondary to peripheral nerve injuries, involvement of sympathetic fibers complications such as Complex Regional Pain Syndrome (CRPS) have been reported. There are no reports available in the distribution of the sympathetic fibers/areas of sensory nerves in the forearm. MATERIALS AND METHODS: The present study aim is an attempt to find the distribution of sympathetic fibers in the anterior branch of medial antebrachial cutaneous nerve of forearm (AMACN), lateral antebrachial cutaneous nerve of forearm (LACN) and superficial branch of radial nerve (SBRN) at cubital fossae. We have studied on 17 fresh human cadaveric AMACN, LACN and SRBN samples. Frozen sections of these nerves were processed by immunohistochemical (tyrosine hydroxylase) method for sympathetic fibers. RESULTS: Sympathetic fibers area (Asym) was found to be more in SBRN when compared to AMACN and LACN. The comparison of the sympathetic index (SI = sympathetic fibers area / total fascicular area of the nerve) between AMACN and LACN (p-value < 0.001), AMACN and SBRN (p-value <0.001), LACN and SBRN (p-value < 0.001) were statistically significant. Sympathetic index (SI) for SBRN was more when compared to AMACN and LACN. SBRN had maximum percentage (5.16%) of Asym when compared with LACN and AMACN. CONCLUSIONS: Sympathetic fibers area (Asym), sympathetic index (SI) and percentage of sympathetic fibers area (Asym %) were found to be more in SBRN when compared with AMACN and LACN. These results of the study might help to explain sympathetic system-related diseases in the area of distribution of AMACN, LACN and SBRN.

Histological and ultrasonographical study of the human superficial branch of the radial nerve at distal forearm and its clinical implications.

PURPOSE: Age as poor prognostic factor following nerve repair may be due to change in intraneural anatomy with age. The purpose of this study is to find out the cross sectional microanatomy of the superficial branch of radial nerve (SBRN) at distal part of forearm for changes in the fascicular, non-fascicular components with respect to age and also to find cross section area of SBRN in healthy volunteers. MATERIAL AND METHODS: Sixty fresh human (37-88-year-old) cadaveric SBRN were collected from the distal part of forearm and studied at different magnifications after histological processing for morphometric analysis - total cross-sectional (Asc), fascicular (Af) and non-fascicular area (Anonf). Fifteen volunteers SBRN cross sectional area was measured by ultrasonography (US). RESULTS: The SBRN was found to have 6-12 fascicles. Morphometric and correlation analysis confirmed that there was a significant increase of total cross section area, with significant increase of interfascicular adipose tissue in relation to advancing age. Ultrasonographic cross-sectional area ranged from 2 to 3.3 mm². CONCLUSIONS: Our study revealed comparatively more adipose tissue in human SBRN with advancing age. These findings may help to explain poor prognosis with advancing age following repair. SBRN ultrasonographical Asc was comparable to histological Asc. Further, it is possible to find Asc of SBRN by non-invasive US study and calculate the fascicular and non-fascicular area using our histological findings.