Effects of an exercise programme for chronically ill and mobility-restricted elderly with structured support by the general practitioner's practice (HOMEfit) - study protocol of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Exercise programmes can be administered successfully as therapeutic agents to patients with a number of chronic diseases and help to improve physical functioning in older adults. Usually, such programmes target either healthy and mobile community-dwelling seniors or elderly individuals living in nursing institutions or special residences. Chronically ill or mobility-restricted individuals, however, are difficult to reach when they live in their own homes.</p> <p>A pilot study has shown good feasibility of a home-based exercise programme that is delivered to this target group through cooperation between general practitioners and exercise therapists. A logical next step involves evaluation of the effects of the programme.</p> <p>Methods/design</p> <p>The study is designed as a randomised controlled trial. We plan to recruit 210 patients (≥ 70 years) in about 15 general practices.</p> <p>The experimental intervention (duration 12 weeks)-a multidimensional home-based exercise programme-is delivered to the participant by an exercise therapist in counselling sessions at the general practitioner's practice and on the telephone. It is based on methods and strategies for facilitating behaviour change according to the Health Action Process Approach (HAPA). The control intervention-baseline physical activities-differs from the experimental intervention with regard to content of the counselling sessions as well as to content and frequency of the promoted activities.</p> <p>Primary outcome is functional lower body strength measured by the "chair-rise" test. Secondary outcomes are: physical function (battery of motor tests), physical activity (step count), health-related quality of life (SF-8), fall-related self-efficacy (FES-I), and exercise self-efficacy (SSA-Scale).</p> <p>The hypothesis that there will be differences between the two groups (experimental/control) with respect to post-interventional chair-rise time will be tested using an ANCOVA with chair-rise time at baseline, treatment group, and study centre effects as explanatory variables. Analysis of the data will be undertaken using the principle of intention-to-treat.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN17727272">ISRCTN17727272</a>.</p

Recruiting Hard-to-Reach Subjects for Exercise Interventions: A Multi-Centre and Multi-Stage Approach Targeting General Practitioners and Their Community-Dwelling and Mobility-Limited Patients

The general practitioner (GP)’s practice appears to be an ideal venue for recruiting community-dwelling older adults with limited mobility. This study (Current Controlled Trials ISRCTN17727272) aimed at evaluating the recruiting process used for a multi-centre exercise intervention (HOMEfit). Each of six steps resulted in an absolute number of patients (N1–N6). Sex and age (for N4–N6) and reasons for dropping out were assessed. Patient database screening (N1–N3) at 15 GP practices yielded N1 = 5,990 patients aged 70 and above who had visited their GP within the past 6 months, N2 = 5,467 after exclusion of institutionalised patients, N3 = 1,545 patients eligible. Using a pre-defined limitation algorithm in order to conserve the practices’ resources resulted in N4 = 1,214 patients (80.3 ± 5.6 years, 68% female), who were then officially invited to the final assessment of eligibility at the GP’s practice. N5 = 434 patients (79.5 ± 5.4 years, 69% female) attended the practice screening (n = 13 of whom had not received an official invitation). Finally, N6 = 209 (79.8 ± 5.2 years, 74% female) were randomised after they were judged eligible and had given their written informed consent to participate in the randomised controlled trial (overall recruitment rate: 4.4%). The general strategy of utilising a GP’s practice to recruit the target group proved beneficial. The data and experiences presented here can help planners of future exercise-intervention studies

New carbamate supports for the preparation of 3'-amino-modified oligonucleotides

A novel approach for the preparation of oligonucleotides carrying amino groups at the 3'-end is described. Several CPG supports having aminoalkyl groups and 3'-amino-2',3'-dideoxynucleosides linked through base-labile carbamate linkages such as 2-(2- nitrophenyl)ethoxycarbonyl and fluorenylmethoxycarbonyl were prepared using two different strategies. These supports are compatible to the standard solid phase phosphite-triester methodology and yield oligonucleotides containing amino groups at the 3'-end. Several properties of the 3'-amino oligonucleotides, such as nuclease resistance, hybridization, and preparation of oligonucleotide conjugates are discussed.Financial support from CICYT (PB92-0043) and E.E.C.C. Biomedicine and Health Programme (BMH1-CT93-1669) is gratefully acknowledged. We thank Drs P. Herdewijn, A. van Aerschot, T. Saison- Behmoaras, and W. Pfleiderer for their helpful suggestions. We are grateful to Marten Wiersma for his technical assistance.Peer reviewe

TEFM (c17orf42) is necessary for transcription of human mtDNA

Here we show that c17orf42, hereafter TEFM (transcription elongation factor of mitochondria), makes a critical contribution to mitochondrial transcription. Inactivation of TEFM in cells by RNA interference results in respiratory incompetence owing to decreased levels of H- and L-strand promoter-distal mitochondrial transcripts. Affinity purification of TEFM from human mitochondria yielded a complex comprising mitochondrial transcripts, mitochondrial RNA polymerase (POLRMT), pentatricopeptide repeat domain 3 protein (PTCD3), and a putative DEAD-box RNA helicase, DHX30. After RNase treatment only POLRMT remained associated with TEFM, and in human cultured cells TEFM formed foci coincident with newly synthesized mitochondrial RNA. Based on deletion mutants, TEFM interacts with the catalytic region of POLRMT, and in vitro TEFM enhanced POLRMT processivity on ss- and dsDNA templates. TEFM contains two HhH motifs and a Ribonuclease H fold, similar to the nuclear transcription elongation regulator Spt6. These findings lead us to propose that TEFM is a mitochondrial transcription elongation factor

SLAIN2 links microtubule plus end–tracking proteins and controls microtubule growth in interphase

SLAIN2’s interactions with multiple different microtubule plus end–tracking proteins stimulate processive microtubule polymerization and ensure proper microtubule organization

Digital Pixel Test Structures implemented in a 65 nm CMOS process

The ALICE ITS3 (Inner Tracking System 3) upgrade project and the CERN EP R&D on monolithic pixel sensors are investigating the feasibility of the Tower Partners Semiconductor Co. 65 nm process for use in the next generation of vertex detectors. The ITS3 aims to employ wafer-scale Monolithic Active Pixel Sensors thinned down to 20 to 40 um and bent to form truly cylindrical half barrels. Among the first critical steps towards the realisation of this detector is to validate the sensor technology through extensive characterisation both in the laboratory and with in-beam measurements. The Digital Pixel Test Structure (DPTS) is one of the prototypes produced in the first sensor submission in this technology and has undergone a systematic measurement campaign whose details are presented in this article. The results confirm the goals of detection efficiency and non-ionising and ionising radiation hardness up to the expected levels for ALICE ITS3 and also demonstrate operation at +20 C and a detection efficiency of 99% for a DPTS irradiated with a dose of $10^{15}$ 1 MeV n$_{\mathrm{eq}}/$cm$^2$. Furthermore, spatial, timing and energy resolutions were measured at various settings and irradiation levels.Comment: Updated threshold calibration method. Implemented colorblind friendly color palette in all figures. Updated reference

Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1

There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source

International audience: Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes

Relevanz geburtshilflicher Parameter für das Auftreten postpartaler Beckenbodeninsuffizienz 18 – 24 Monate nach der Geburt des ersten Kindes unter Einbeziehung der 3D-Perinealsonographie

Ziel dieser prospektiven klinischen Studie war es, biometrische Messungen des M. levator ani zwei Jahre nach der ersten Entbindung zu erheben und diese in Bezug zu setzen zu verschiedenen anamnestischen Variablen. Außerdem wurden die Messwerte mit den zwei Tage pp erhobenen Werten verglichen. Das initiale Studienkollektiv bestand aus 130 Primiparae, die Rücklaufquote beim Follow-up betrug 59,2% (n=77), der durchschnittliche Untersuchungszeitpunkt lag 21,4 Monate pp. Es erfolgte eine 3D-Perinealsonographie sowie eine gynäkologische Untersuchung zur Evaluation eines Descensus uteri und vaginae, jeweils in Ruhe und während eines Valsalva-Manövers. Beckenbodenfunktionsstörungen wurden mithilfe eines Fragebogens erfasst. 18-24 Monate pp fanden sich bei den vaginal entbundenen Frauen im Vergleich zu den per Sectio entbundenen Frauen signifikant größere Werte des Levatorspalts. Außerdem bestanden signifikante Korrelationen zwischen dem Alter und dem BMI der Primiparae mit den sonographisch erfassten Parametern. Insgesamt berichteten 36,8% der Frauen beim Follow-up über eine Belastungsinkontinenz, 42,1% über eine Drangsymptomatik, 27,3% über eine regelmäßige Nykturie, 6,5% über eine Stuhlinkontinenz und 25,0% über eine Dyspareunie. Der seitliche und der a.-p. Durchmesser des Levatorhiatus sowie die Levatorfläche zeigten einen signifikanten Zusammenhang mit dem Auftreten einer Belastungsinkontinenz. Desweiteren bestand auch ein statistisch signifikanter Zusammenhang mit dem Auftreten eines Descensus vaginae vom Typ der Zystozele. Schwangerschaftsinkontinenz war ebenso wie ein mütterliches Alter über 30 Jahre und ein BMI über 30kg/m2 signifikant mit dem Erleben von Belastungsinkontinenz assoziiert. Die Dauer der Austreibungsperiode war bei den Frauen, die eine Inkontinenz entwickelt hatten, signifikant kürzer als bei den Frauen ohne Belastungsinkontinenz. Zusammenfassend lässt sich sagen, dass geburtsbedingte Veränderungen der Beckenbodenarchitektur sowohl direkt pp als auch noch zwei Jahre später mit der 3D- Perinealsonographie einfach visualisiert werden können. Die prädiktive Wertigkeit der Beckenbodensonographie für funktionelle Beckenbodenstörungen unmittelbar pp lässt sich aus den erhobenen Daten jedoch nicht abschließend beurteilen