Safe dissection of the distally based anterolateral thigh flap.

Background The distally based anterolateral thigh (ALT) flap is an interesting reconstructive solution for complex soft tissue defects of the knee. In spite of a low donor site morbidity and wide covering surface as well as arch of rotation, it has never gained popularity among reconstructive surgeons. Venous congestion and difficult flap dissection in the presence of a variable anatomy of the vascular pedicle are the possible reasons.Methods An anatomical study of 15 cadaver legs was performed to further clarify the blood supply of the distally based ALT. Our early experience with the use of preoperative angiography and a safe flap design modification that avoids distal intramuscular skeletonization of the vascular pedicle and includes a subcutaneous strip ranging from the distal end of the flap to the pivot point is presented.Results The distally based ALT presents a constant and reliable retrograde vascular contribution from the superior genicular artery. Preoperative angiography reliably identified and avoided critical Shieh Type II pedicled flaps. The preservation of a subcutaneous strip ranging from the distal flap end to the upper knee was associated with the absence of venous congestion in a short case series.Conclusions Preoperative angiography and a flap design modification are proposed to allow the safe transfer of the distally based ALT to reconstruct soft tissue defects of the knee.

The v-y latissimus dorsi musculocutaneous flap in the reconstruction of large posterior chest wall defects.

Posterior chest wall defects are frequently encountered after excision of tumors as a result of trauma or in the setting of wound dehiscence after spine surgery. Various pedicled fasciocutaneous and musculocutaneous flaps have been described for the coverage of these wounds. The advent of perforator flaps has allowed the preservation of muscle function but their bulk is limited. Musculocutaneous flaps remain widely employed. The trapezius and the latissimus dorsi (LD) flaps have been used extensively for upper and middle posterior chest wounds, respectively. Their bulk allows for obliteration of the dead space in deep wounds. The average width of the LD skin paddle is limited to 10-12 cm if closure of the donor site is expected without skin grafting. In 2001 a modification of the skin paddle design was introduced in order to allow large flaps to be raised without requiring grafts or flaps for donor site closure. This V-Y pattern allows coverage of large anterior chest defects after mastectomy. We have modified this flap to allow its use for posterior chest wall defects. We describe the flap design, its indications, and its limitations with three clinical cases. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .

Donor-site morbidity of the sensate extended lateral arm flap.

The free extended lateral arm flap (ELAF) has gained increasing popularity thank to its slimness and versatility, longer neurovascular pedicle, and greater flap size when compared with the original flap design. The aim of this study was to assess the donor-site morbidity associated with this extended procedure. A retrospective study of 25 consecutive patients analyzing postoperative complications using a visual analogue scale questionnaire revealed high patients satisfaction and negligible donor-site morbidity of the ELAF. Scar visibility was the commonest negative outcome. Impaired mobility of the elbow had the highest correlation with patient dissatisfaction. Sensory deficits or paresthetic disorders did not affect patient satisfaction. The extension of the lateral arm flap and positioning over the lateral humeral epicondyle is a safe and well-accepted procedure with minimal donor-site morbidity. To optimize outcomes, a maximal flap width of 6 or 7 cm and intensive postoperative mobilization therapy is advisable.

Radial forearm free flap donor site morbidity: ulnar-based transposition flap vs split-thickness skin graft.

OBJECTIVES: To evaluate morbidity associated with the radial forearm free flap donor site and to compare functional and aesthetic outcomes of ulnar-based transposition flap (UBTF) vs split-thickness skin graft (STSG) closure of the donor site.¦DESIGN: Case-control study.¦SETTING: Tertiary care institution.¦PATIENTS: The inclusion criteria were flap size not exceeding 30 cm(2), patient availability for a single follow-up visit, and performance of surgery at least 6 months previously. Forty-four patients were included in the study and were reviewed. Twenty-two patients had UBTF closure, and 22 had STSG closure.¦MAIN OUTCOME MEASURES: Variables analyzed included wrist mobility, Michigan Hand Outcomes Questionnaire scores, pinch and grip strength (using a dynamometer), and hand sensitivity (using monofilament testing over the radial nerve distribution). In analyses of operated arms vs nonoperated arms, variables obtained only for the operated arms included Vancouver Scar Scale scores and visual analog scale scores for Aesthetics and Overall Arm Function.¦RESULTS: The mean (SD) wrist extension was significantly better in the UBTF group (56.0° [10.4°] for nonoperated arms and 62.0° [9.7°] for operated arms) than in the STSG group (59.0° [7.1°] for nonoperated arms and 58.4° [12.1°] for operated arms) (P = .02). The improvement in wrist range of motion for the UBTF group approached statistical significance (P = .07). All other variables (Michigan Hand Outcomes Questionnaire scores, pinch and grip strength, hand sensitivity, and visual analog scale scores) were significantly better for nonoperated arms vs operated arms, but no significant differences were observed between the UBTF and STSG groups.¦CONCLUSIONS: The radial forearm free flap donor site carries significant morbidity. Donor site UBTF closure was associated with improved wrist extension and represents an alternative method of closure for small donor site defects.

Rational design of an organometallic glutathione transferase inhibitor.

Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

Using active learning for monitoring networks design: The example of wind power plants sites evaluation

Locating new wind farms is of crucial importance for energy policies of the next decade. To select the new location, an accurate picture of the wind fields is necessary. However, characterizing wind fields is a difficult task, since the phenomenon is highly nonlinear and related to complex topographical features. In this paper, we propose both a nonparametric model to estimate wind speed at different time instants and a procedure to discover underrepresented topographic conditions, where new measuring stations could be added. Compared to space filling techniques, this last approach privileges optimization of the output space, thus locating new potential measuring sites through the uncertainty of the model itself.

Design and evaluation of a solid sampler for the monitoring of airborne 1,6-hexamethylene diisocyanate (HDI) and its prepolymers in 2-component spray painting

An active, solvent-free solid sampler was developed for the collection of 1,6-hexamethylene diisocyanate (HDI) aerosol and prepolymers. The sampler was made of a filter impregnated with 1-(2-methoxyphenyl)piperazine contained in a filter holder. Interferences with HDI were observed when a set of cellulose acetate filters and a polystyrene filter holder were used; a glass fiber filter and polypropylene filter cassette gave better results. The applicability of the sampling and analytical procedure was validated with a test chamber, constructed for the dynamic generation of HDI aerosol and prepolymers in commercial two-component spray paints (Desmodur(R) N75) used in car refinishing. The particle size distribution, temporal stability, and spatial uniformity of the simulated aerosol were established in order to test the sample. The monitoring of aerosol concentrations was conducted with the solid sampler paired to the reference impinger technique (impinger flasks contained 10 mL of 0.5 mg/mL 1-(2-methoxyphenyl)piperazine in toluene) under a controlled atmosphere in the test chamber. Analyses of derivatized HDI and prepolymers were carried out by using high-performance liquid chromatography and ultraviolet detection. The correlation between the solvent-free and the impinger techniques appeared fairly good (Y = 0.979X - 0.161; R = 0.978), when the tests were conducted in the range of 0.1 to 10 times the threshold limit value (TLV) for HDI monomer and up to 60-mu-g/m3 (3 U.K. TLVs) for total -N = C = O groups.

Experimental design for acquiring relevant data to address the issue of comparing consecutively manufactured tools and firearms

The comparison of consecutively manufactured tools and firearms has provided much, but not all, of the basis for the profession of firearm and toolmark examination. The authors accept the fundamental soundness of this approach but appeal to the experimental community to close two minor gaps in the experimental procedure. We suggest that "blinding" and attention to appropriateness of other experimental conditions that would consolidate the foundations of our profession. We do not suggest that previous work is unsound.

New concepts for the design of dermal substitutes

Objectives: Skin can be partially regenerated after full thickness defects by collagen matrices, In this study, we identified the main limitations of induced regeneration aiming to improve the design of dermal matrices. Methods: Single mice received a 1 cm2, full thickness skin wound on the dorsum, which were grafted with collagen-GAG matrices or left ungrafted. The healing modulation induced by the collagen-GAG matrices was compared to spontaneous healing and to custom designed, bioactive, poly-N-Acetyl- Glucosamine (NAG) matrices. Wound staging was based on macroscopic, histological and immunhistochemical analysis on days 3, 7, 10 and 21 post wounding. Results: Cell density was higher in spontaneously granulating wounds compared to grafted wounds. While grafted wounds exhibited increased levels of cell proliferation on days 7 and 10, vascularity was dramatically reduced. NAG scaffolds accelerated both angiogenesis and wound re-epithelialization. Conclusions: Since slow integration and revascularization severely limit the engraftment of clinically used dermal scaffolds, the design of dermal matrices using bioactive materials represent the next step in skin regeneration.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Design and analysis of ChIP-Seq experiments for nuclear factor I DNA-binding proteins

SUMMARY : Eukaryotic DNA interacts with the nuclear proteins using non-covalent ionic interactions. Proteins can recognize specific nucleotide sequences based on the sterical interactions with the DNA and these specific protein-DNA interactions are the basis for many nuclear processes, e.g. gene transcription, chromosomal replication, and recombination. New technology termed ChIP-Seq has been recently developed for the analysis of protein-DNA interactions on a whole genome scale and it is based on immunoprecipitation of chromatin and high-throughput DNA sequencing procedure. ChIP-Seq is a novel technique with a great potential to replace older techniques for mapping of protein-DNA interactions. In this thesis, we bring some new insights into the ChIP-Seq data analysis. First, we point out to some common and so far unknown artifacts of the method. Sequence tag distribution in the genome does not follow uniform distribution and we have found extreme hot-spots of tag accumulation over specific loci in the human and mouse genomes. These artifactual sequence tags accumulations will create false peaks in every ChIP-Seq dataset and we propose different filtering methods to reduce the number of false positives. Next, we propose random sampling as a powerful analytical tool in the ChIP-Seq data analysis that could be used to infer biological knowledge from the massive ChIP-Seq datasets. We created unbiased random sampling algorithm and we used this methodology to reveal some of the important biological properties of Nuclear Factor I DNA binding proteins. Finally, by analyzing the ChIP-Seq data in detail, we revealed that Nuclear Factor I transcription factors mainly act as activators of transcription, and that they are associated with specific chromatin modifications that are markers of open chromatin. We speculate that NFI factors only interact with the DNA wrapped around the nucleosome. We also found multiple loci that indicate possible chromatin barrier activity of NFI proteins, which could suggest the use of NFI binding sequences as chromatin insulators in biotechnology applications. RESUME : L'ADN des eucaryotes interagit avec les protéines nucléaires par des interactions noncovalentes ioniques. Les protéines peuvent reconnaître les séquences nucléotidiques spécifiques basées sur l'interaction stérique avec l'ADN, et des interactions spécifiques contrôlent de nombreux processus nucléaire, p.ex. transcription du gène, la réplication chromosomique, et la recombinaison. Une nouvelle technologie appelée ChIP-Seq a été récemment développée pour l'analyse des interactions protéine-ADN à l'échelle du génome entier et cette approche est basée sur l'immuno-précipitation de la chromatine et sur la procédure de séquençage de l'ADN à haut débit. La nouvelle approche ChIP-Seq a donc un fort potentiel pour remplacer les anciennes techniques de cartographie des interactions protéine-ADN. Dans cette thèse, nous apportons de nouvelles perspectives dans l'analyse des données ChIP-Seq. Tout d'abord, nous avons identifié des artefacts très communs associés à cette méthode qui étaient jusqu'à présent insoupçonnés. La distribution des séquences dans le génome ne suit pas une distribution uniforme et nous avons constaté des positions extrêmes d'accumulation de séquence à des régions spécifiques, des génomes humains et de la souris. Ces accumulations des séquences artéfactuelles créera de faux pics dans toutes les données ChIP-Seq, et nous proposons différentes méthodes de filtrage pour réduire le nombre de faux positifs. Ensuite, nous proposons un nouvel échantillonnage aléatoire comme un outil puissant d'analyse des données ChIP-Seq, ce qui pourraient augmenter l'acquisition de connaissances biologiques à partir des données ChIP-Seq. Nous avons créé un algorithme d'échantillonnage aléatoire et nous avons utilisé cette méthode pour révéler certaines des propriétés biologiques importantes de protéines liant à l'ADN nommés Facteur Nucléaire I (NFI). Enfin, en analysant en détail les données de ChIP-Seq pour la famille de facteurs de transcription nommés Facteur Nucléaire I, nous avons révélé que ces protéines agissent principalement comme des activateurs de transcription, et qu'elles sont associées à des modifications de la chromatine spécifiques qui sont des marqueurs de la chromatine ouverte. Nous pensons que lés facteurs NFI interagir uniquement avec l'ADN enroulé autour du nucléosome. Nous avons également constaté plusieurs régions génomiques qui indiquent une éventuelle activité de barrière chromatinienne des protéines NFI, ce qui pourrait suggérer l'utilisation de séquences de liaison NFI comme séquences isolatrices dans des applications de la biotechnologie.

Study design for technology assessment: critical issues.

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.

Rekonstruktion von Oberkieferdefekten mit einem freien Skapula-angle-Lappen [Reconstruction of maxillary defects using a free scapular angle flap].

BACKGROUND: In addition to prosthetic rehabilitation, maxillary defects can also be surgically reconstructed. Soft-tissue reconstruction employs a radial forearm or latissimus dorsi muscle flap, while bony reconstruction can be achieved using a fibula, iliac crest, or scapular flap. Reconstruction using a scapular flap is further divided into two subgroups: the traditional scapular flap with the circumflex scapular artery as the donor vessel and the scapular angle flap with the angular artery originating from the thoracodorsal artery as the donor vessel. MATERIALS AND METHODS: We report on four patients who underwent successful reconstruction with a free scapular angle flap between 2009 and 2011, following maxillary resection due to malignancy. RESULTS: Vertical positioning of the scapular angle flap enables reconstruction of the facial contour, whereas its horizontal alignment and microvascular anastomosis makes a bony reconstruction of the hard palate possible. CONCLUSIONS: The versatility, low rate of donor site morbidity and shape of the scapular angle flap--which resembles that of the hard palate--render it ideal for plastic reconstruction. The suitability of bone quality for dental rehabilitation with implants is a topic of controversial discussion. The scapular angle flap represents an alternative to obturator prosthesis for the reconstruction of maxillary defects ≥ grade I according to Okay et al.

Docking, virtual high throughput screening and in silico fragment-based drug design.

ABSTRACT The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high throughput screening and fragment-based ligand design.