Combination of anodal tDCS of the cerebellum with a goal-oriented motor training to treat cervical dystonia: a pilot case series.

Background: Transcranial Direct Current Stimulation (tDCS) of the cerebellum shows promise for the treatment of dystonia. Specific motor rehabilitation programs have also been developed in this context. However, the combination of these two approaches has not yet been evaluated to determine their therapeutic potential. Methods: We report a series of 5 patients with cervical dystonia (CD) poorly controlled by botulinum toxin injections. They were initially treated by a protocol of repeated daily sessions (for 3 or 5 days) of cerebellar anodal tDCS (cer-atDCS) applied alone. In a second time, additional protocols of cer-atDCS were performed in combination with a program of goal-oriented motor training exercises (Mot-Training), specifically developed for the treatment of CD. The clinical impact of the procedures was assessed on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results: Compared to baseline, the maximum percentage of TWSTRS total score improvement was 37% on average after cer-atDCS performed alone (p = 0.147, not significant) and 53% on average after cer-atDCS combined with Mot-Training (p = 0.014, significant). The TWSTRS pain and functional handicap subscores also improved after the combined protocol. A score of (+3) to (+5) was rated on the TWSTRS response scale after cer-atDCS performed alone or the combined protocol, corresponding to a moderate to striking improvement on dystonia and pain. This improvement lasted longer after the combined protocol than after cer-atDCS alone (3.4 vs. 1.4 months on average, p = 0.011). Conclusion: The combination of cer-atDCS with Mot-Training produced a greater and more prolonged improvement than the application of cer-atDCS alone. Such a combined therapeutic procedure is easy to perform and opens important perspectives in the long-term treatment of CD. These results remain to be confirmed by a randomized sham-controlled trial on a larger sample.

Assessment of axial rotation movement in cervical dystonia using cone-beam computed tomography.

BACKGROUND: Cervical dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal postures of the head and neck. Botulinum neurotoxin injection is the first-line treatment. Imaging determination of the cervical segments involved (lower or upper according to the torticollis-torticaput [COL-CAP] Classification) is an aid in determining the muscles to be injected. We aimed to clarify the impact of dystonia on posture and rotational movement of cervical vertebrae in the transverse plane. METHODS: A comparative study was conducted in a movement disorders department. Ten people with cervical dystonia and 10 matched healthy subjects (without cervical dystonia) were recruited. 3-D images of posture and cervical range of motion in axial rotation in the sitting position were recorded by using a cone-beam CT scanner. Range of rotational motion of the upper cervical spine from the occipital bone to fourth cervical vertebra was measured and compared between the two groups. FINDINGS: The head posture analysis showed that the total cervical spine position was more significantly distant from the neutral position for people with dystonia than healthy subjects (p = 0.007). The rotational range of motion of the cervical spine was significantly lower in cervical dystonia participants than in healthy subjects for the total (p = 0.026) and for upper cervical spine (p = 0.004). INTERPRETATION: We demonstrated, by means of cone-beam CT, that the disorganization of movements due to cervical dystonia affected the upper cervical spine and mostly the atlantoaxial joint. The involvement of rotator muscles at this cervical level should be considered more in treatments.

Genome Analysis of a Variant of Streptomyces coelicolor M145 with High Lipid Content and Poor Ability to Synthetize Antibiotics.

Streptomyces coelicolor M145 is a model strain extensively studied to elucidate the regulation of antibiotic biosynthesis in Streptomyces species. This strain abundantly produces the blue polyketide antibiotic, actinorhodin (ACT), and has a low lipid content. In a process designed to delete the gene encoding the isocitrate lyase (sco0982) of the glyoxylate cycle, an unexpected variant of S. coelicolor was obtained besides bona fide sco0982 deletion mutants. This variant produces 7- to 15-fold less ACT and has a 3-fold higher triacylglycerol and phosphatidylethanolamine content than the original strain. The genome of this variant was sequenced and revealed that 704 genes were deleted (9% of total number of genes) through deletions of various sizes accompanied by the massive loss of mobile genetic elements. Some deletions include genes whose absence could be related to the high total lipid content of this variant such as those encoding enzymes of the TCA and glyoxylate cycles, enzymes involved in nitrogen assimilation as well as enzymes belonging to some polyketide and possibly trehalose biosynthetic pathways. The characteristics of this deleted variant of S. coelicolor are consistent with the existence of the previously reported negative correlation existing between lipid content and antibiotic production in Streptomyces species.

Clustering-based preprocessing method for lipidomic data analysis: application for the evolution of newborn skin surface lipids from birth until 6 months.

After life in utero and birth, the skin is submitted to an important process of adaptation to a relatively dry gaseous environment. Skin surface lipids (SSLs) contribute actively to the protection of the skin barrier. Within this context, our objective was to study the evolution of each lipid compound during the postnatal period. SSLs were collected from six newborns a few days after birth until the age of 6 months. Seventy samples were analyzed using high-temperature gas chromatography coupled to mass spectrometry (HT-GC/MS). The use of separative techniques coupled to mass spectrometry for the analysis of samples containing complex mixtures of lipids generates a large volume of data which renders the results interpretation very difficult. In this study, we propose a new approach to handle the raw data, a clustering-based preprocessing method (CB-PPM), in order to achieve (1) volume reduction of data provided by each chromatogram without loss of information, (2) alignment of time retention shift between different runs, (3) clustering of mass spectra of the same molecule in one qualitative group, (4) and integration of all data into a single matrix to be explored by chemometric tools. This approach allowed us to gather data variations in 256 qualitative groups and therefore enabled us to highlight the variation of compounds including those of low intensity. Moreover, the representation of all data gathered in one matrix rendered reading of the results rapid and efficient. Thus, using this approach, we have demonstrated an increase of cholesterol esterification with epidermal fatty acids (C20 to C25) with age. This epidermis participation in SSL production at a molecular level in the first period of life has not been previously shown. These data can be very interesting for the development and improvement of products destined for the protection of infant skin. Graphical abstract ᅟ.

Ammoides pusilla (Apiaceae) essential oil: Activity against Acanthamoeba castellanii Neff.

Acanthamoeba is a free-living amoeba genus that causes several diseases namely, amoebic keratitis which is a painful sight threatening eyes disease. Its treatment is difficult and the exploration for new drugs is very important. The main objective of the present study was to evaluate the chemical composition of the Essential Oils (EO) obtained from leaves and flowers and aerial parts of Ammoides pusilla by an alternative method "Hydrodistillation''. Identification and quantification were realized by Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography with Flame Ionization Detection (GC-FID). The main components of leaves and flowers and aerials parts were thymol (39.6% and 33.05%), γ-terpinene (28.97% and 28.19%), p-cymene (13.69% and 15.31%) and thymol methyl ether (7.33% and 8.91%), respectively. The antiparasitic activity of the EO was evaluated against Acanthamoeba castellanii Neff by the Alamar Blue® assay. Results showed that Ammoides pusilla amoebicidal activity from leaves and flowers essential oil (IC50 = 65.32 ± 5.43 µg/mL) was more important than those of aerial parts EO (IC50 = 97.18 ± 1.43 µg/ml).

Manual Dexterity in Schizophrenia-A Neglected Clinical Marker?

Impaired manual dexterity is commonly observed in schizophrenia. However, a quantitative description of key sensorimotor components contributing to impaired dexterity is lacking. Whether the key components of dexterity are differentially affected and how they relate to clinical characteristics also remains unclear. We quantified the degree of dexterity in 35 stabilized patients with schizophrenia and in 20 age-matched control subjects using four visuomotor tasks: (i) force tracking to quantify visuomotor precision, (ii) sequential finger tapping to measure motor sequence recall, (iii) single-finger tapping to assess temporal regularity, and (iv) multi-finger tapping to measure independence of finger movements. Diverse clinical and neuropsychological tests were also applied. A patient subgroup (N = 15) participated in a 14-week cognitive remediation protocol and was assessed before and after remediation. Compared to control subjects, patients with schizophrenia showed greater error in force tracking, poorer recall of tapping sequences, decreased tapping regularity, and reduced degree of finger individuation. A composite performance measure discriminated patients from controls with sensitivity = 0.79 and specificity = 0.9. Aside from force-tracking error, no other dexterity components correlated with antipsychotic medication. In patients, some dexterity components correlated with neurological soft signs, Positive and Negative Syndrome Scale (PANSS), or neuropsychological scores. This suggests differential cognitive contributions to these components. Cognitive remediation lead to significant improvement in PANSS, tracking error, and sequence recall (without change in medication). These findings show that multiple aspects of sensorimotor control contribute to impaired manual dexterity in schizophrenia. Only visuomotor precision was related to antipsychotic medication. Good diagnostic accuracy and responsiveness to treatment suggest that manual dexterity may represent a useful clinical marker in schizophrenia.

Quantitative Proteomics Analysis Confirmed Oxidative Metabolism Predominates in Streptomyces coelicolor versus Glycolytic Metabolism in Streptomyces lividans.

Recent physiological studies indicated that S. lividans metabolism was mainly glycolytic, whereas S. coelicolor metabolism was mainly oxidative. To determine whether such metabolic characteristics were correlated with consistent proteomics features, a comparative label-free, shotgun proteomics analysis of these strains was carried out. Among 2024 proteins identified, 360 showed significant differences in abundance between the strains. This study revealed that S. coelicolor catabolized glucose less actively than S. lividans, whereas the amino acids present in the medium were catabolized less actively by S. lividans than by S. coelicolor. The abundance of glycolytic proteins in S. lividans was consistent with its high glycolytic activity, whereas the abundance of proteins involved in the catabolism of amino acids in S. coelicolor provided an explanatory basis for its predominantly oxidative metabolism. In this study, conducted under conditions of low O2 availability, proteins involved in resistance to oxidative stress and those belonging to a DosR-like dormancy regulon were abundant in S. coelicolor, whereas tellurium resistance proteins were abundant in S. lividans. This indicated that the strains reacted differently to O2 limitation. Proteins belonging to the CDA, RED, and ACT pathways, usually highly expressed in S. coelicolor, were not detected under these conditions, whereas proteins of siderophores, 5-hydroxyectoine, and terpenoid biosynthetic pathways were present.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) for Rapid Determination of Microbial Cell Lipid Content: Correlation with Gas Chromatography-Mass Spectrometry (GC-MS).

There is a growing interest worldwide for the production of renewable oil without mobilizing agriculture lands; fast and reliable methods are needed to identify highly oleaginous microorganisms of potential industrial interest. The aim of this study was to demonstrate the relevance of attenuated total reflection (ATR) spectroscopy to achieve this goal. To do so, the total lipid content of lyophilized samples of five Streptomyces strains with varying lipid content was assessed with two classical quantitative but time-consuming methods, gas chromatography-mass spectrometry (GC-MS) and ATR Fourier transform infrared (ATR FT-IR) spectroscopy in transmission mode with KBr pellets and the fast ATR method, often questioned for its lack of reliability. A linear correlation between these three methods was demonstrated allowing the establishment of equations to convert ATR values expressed as CO/amide I ratio, into micrograms of lipid per milligram of biomass. The ATR method proved to be as reliable and quantitative as the classical GC-MS and FT-IR in transmission mode methods but faster and more reproducible than the latter since it involves far less manipulation for sample preparation than the two others. Attenuated total reflection could be regarded as an efficient fast screening method to identify natural or genetically modified oleaginous microorganisms by the scientific community working in the field of bio-lipids.

Does dystonic muscle activity affect sense of effort in cervical dystonia?

BACKGROUND: Focal dystonia has been associated with deficient processing of sense of effort cues. However, corresponding studies are lacking in cervical dystonia (CD). We hypothesized that dystonic muscle activity would perturb neck force control based on sense of effort cues. METHODS: Neck extension force control was investigated in 18 CD patients with different clinical features (7 with and 11 without retrocollis) and in 19 control subjects. Subjects performed force-matching and force-maintaining tasks at 5% and 20% of maximum voluntary contraction (MVC). Three task conditions were tested: i) with visual force feedback, ii) without visual feedback (requiring use of sense of effort), iii) without visual feedback, but with neck extensor muscle vibration (modifying muscle afferent cues). Trapezius muscle activity was recorded using electromyography (EMG). RESULTS: CD patients did not differ in task performance from healthy subjects when using visual feedback (ANOVA, p>0.7). In contrast, when relying on sense of effort cues (without visual feedback, 5% MVC), force control was impaired in patients without retrocollis (p = 0.006), but not in patients with retrocollis (p>0.2). Compared to controls, muscle vibration without visual feedback significantly affected performance in patients with retrocollis (p<0.001), but not in patients without retrocollis. Extensor EMG during rest, included as covariate in ANOVA, explained these group differences. CONCLUSION: This study shows that muscle afferent feedback biases sense of effort cues when controlling neck forces in patients with CD. The bias acts on peripheral or central sense of effort cues depending on whether the task involves dystonic muscles. This may explain why patients with retrocollis more accurately matched isometric neck extension forces. This highlights the need to consider clinical features (pattern of dystonic muscles) when evaluating sensorimotor integration in CD.

[Not Available]. / Les produits d'embaumement égyptiens : nouvelles données pharmacologiques.

Today, the development of analytic methods brings new scientific insights into the research on the mummification process used by embalmers in ancient Egypt. The application of these techniques of molecular analysis, elementary analysis, botanical analysis and bibliographic analysis of ancient texts allows us to know the composition of mummification balms and material involved in the conservation of the body. Such substances, which are mineral, animal or plant material, played a practical and a symbolic part in the composition of balms used for the preservation of mummified bodies and therefore in the passage to the eternal life after the death. The comparison of analysis results can inform us about changes in embalming techniques depending of the time, the place of mummification, the deceased's social status. However the number of mummies studied is very small compared to the number of bodies that were mummified. Finally the techniques of mummification and making balms were very variable according to practitioners and their modus operandi. Today, using these technic of chemical analysis and medical imaging techniques, we can authenticate and reconstruct the history of museum pieces, as we have done in the unpublished studies conducted in support of literature data previously collected.

Upper Limb Outcome Measures Used in Stroke Rehabilitation Studies: A Systematic Literature Review.

BACKGROUND: Establishing which upper limb outcome measures are most commonly used in stroke studies may help in improving consensus among scientists and clinicians. OBJECTIVE: In this study we aimed to identify the most commonly used upper limb outcome measures in intervention studies after stroke and to describe domains covered according to ICF, how measures are combined, and how their use varies geographically and over time. METHODS: Pubmed, CinHAL, and PeDRO databases were searched for upper limb intervention studies in stroke according to PRISMA guidelines and477 studies were included. RESULTS: In studies 48different outcome measures were found. Only 15 of these outcome measures were used in more than 5% of the studies. The Fugl-Meyer Test (FMT)was the most commonly used measure (in 36% of studies). Commonly used measures covered ICF domains of body function and activity to varying extents. Most studies (72%) combined multiple outcome measures: the FMT was often combined with the Motor Activity Log (MAL), the Wolf Motor Function Test and the Action Research Arm Test, but infrequently combined with the Motor Assessment Scale or the Nine Hole Peg Test. Key components of manual dexterity such as selective finger movements were rarely measured. Frequency of use increased over a twelve-year period for the FMT and for assessments of kinematics, whereas other measures, such as the MAL and the Jebsen Taylor Hand Test showed decreased use over time. Use varied largely between countries showing low international consensus. CONCLUSIONS: The results showed a large diversity of outcome measures used across studies. However, a growing number of studies used the FMT, a neurological test with good psychometric properties. For thorough assessment the FMT needs to be combined with functional measures. These findings illustrate the need for strategies to build international consensus on appropriate outcome measures for upper limb function after stroke.

Baseline Features Influencing the Effectiveness of Retraining Therapy for Writer's Cramp.

Background: The effectiveness of retraining therapy (RT) for writer's cramp is difficult to predict and its determinants are unknown. Methods: We examined factors potentially predicting improved legibility after RT in patients with writer's cramp (WC). We reviewed the files of 693 WC patients treated with RT from 1995 to 2009. Standardized assessments were made both at baseline and after 2 months of RT in 305 patients. The effect of RT on legibility was evaluated by using the handwriting subscore of the Burke-Fahn-Marsden (BFM) disability scale. Initial and final handwriting samples were blindly scored in random order. Associations between WC patterns and changes in legibility were identified by uni- and multivariable analyses. Results: Legibility improved by ≥1 point in the BFM handwriting subscore in 93 patients (31%). WC patients who improved were more likely to have synergic dystonic patterns involving the wrist and forearm (60% vs. 40%; P = 0.03) and less likely to have flexion of fingers F3 to F5 (19% vs. 81%; P = 0.017). Outcome was not related to gender, age, or dystonia duration. Our results confirm that retraining therapy could improve legibility in patients with writer's cramp. Conclusions: The pattern of writer's cramp can help to identify patients who are most likely to benefit from retraining therapy, regardless of age, gender, and disease duration.

Establishing high temperature gas chromatographic profiles of non-polar metabolites for quality assessment of African traditional herbal medicinal products.

The quality assessment of African traditional herbal medicinal products is a difficult challenge since they are complex mixtures of several herbal drug or herbal drug preparations. The plant source is also often unknown and/or highly variable. Plant metabolites chromatographic profiling is therefore an important tool for quality control of such herbal products. The objective of this work is to propose a protocol for sample preparation and gas chromatographic profiling of non-polar metabolites for quality control of African traditional herbal medicinal products. The methodology is based on the chemometric assessment of chromatographic profiles of non-polar metabolites issued from several batches of leaves of Combretum micranthum and Mitracarpus scaber by high temperature gas chromatography coupled to mass spectrometry, performed on extracts obtained in refluxed dichloromethane, after removal of chlorophyll pigments. The method using high temperature gas chromatography after dichloromethane extraction allows detection of most non-polar bioactive and non-bioactive metabolites already identified in leaves of both species. Chemometric data analysis using Principal Component Analysis and Partial Least Squares after Orthogonal Signal Correction applied to chromatographic profiles of leaves of Combretum micranthum and Mitracarpus scaber showed slight batch to batch differences, and allowed clear differentiation of the two herbal extracts.

Impaired force control in writer's cramp showing a bilateral deficit in sensorimotor integration.

BACKGROUND: Abnormal cortical processing of sensory inputs has been found bilaterally in writer's cramp (WC). This study tested the hypothesis that patients with WC have an impaired ability to adjust grip forces according to visual and somatosensory cues in both hands. METHODS: A unimanual visuomotor force-tracking task and a bimanual sense of effort force-matching task were performed by WC patients and healthy controls. RESULTS: In visuomotor tracking, WC patients showed increased error, greater variability, and longer release duration than controls. In the force-matching task, patients underestimated, whereas controls overestimated, the force applied in the other hand. Visuomotor tracking and force matching were equally impaired in both the symptomatic and nonsymptomatic hand in WC patients. CONCLUSIONS: This study provides evidence of bilaterally impaired grip-force control in WC, when using visual or sense of effort cues. This suggests a generalized subclinical deficit in sensorimotor integration in WC.

Chemometric approach for investigating the skin surface lipids (SSLs) composition: influence of geographical localization.

Skin surface lipids (SSLs), arising from both sebaceous glands and skin removal, form a complex lipid mixture composed of free fatty acids and neutral lipids. They are present in the hydrolipidic film and have a close relationship with the stratum corneum lipids. Thus, SSLs participate in the barrier function. One can expect a physiological adaptation of the SSLs composition according to geographical localization or skin pigmentation. In this study, SSLs obtained from three groups of volunteers (light and dark skin, living in France and dark skin, living in Ivory Coast) have been investigated. High-temperature gas chromatography/mass spectrometry has been used to study SSLs composition. The variability in the SSLs chromatographic profiles has been investigated, using chemometric methods which allowed us to highlight the sapienic acid (C16: 1Δ6) as discriminant according to geographical localization. This result is of a great interest regarding sapienic acid properties. However, no significant variation has been detected following skin pigmentation. In parallel, SSLs Raman spectra were collected in order to determine the organization and the conformational order of lipids. The spectral data treatment revealed discriminant variation in the υ C-C stretching region revealing changes in the conformational order of the SSLs following geographical localization.

High-temperature gas chromatography-mass spectrometry for skin surface lipids profiling.

Skin surface lipids (SSLs) arising from both sebaceous glands and skin removal form a complex lipid mixture composed of free fatty acids and neutral lipids. High-temperature gas chromatography coupled with electron impact or chemical ionization mass spectrometry was used to achieve a simple analytical protocol, without prior separation in classes and without prior cleavage of lipid molecules, in order to obtain simultaneously i) a qualitative characterization of the individual SSLs and ii) a quantitative evaluation of lipid classes. The method was first optimized with SSLs collected from the forehead of a volunteer. More than 200 compounds were identified in the same run. These compounds have been classified in five lipid classes: free fatty acids, hydrocarbons, waxes, sterols, and glycerides. The advantage to this method was it provided structural information on intact compounds, which is new for cholesteryl esters and glycerides, and to obtain detailed fingerprints of the major SSLs. These fingerprints were used to compare the SSL compositions from different body areas. The squalene/cholesterol ratio was used to determine the balance between sebaceous secretion and skin removal. This method could be of general interest in fields where complex lipid mixtures are involved.

Somatosensory cortical remodelling after rehabilitation and clinical benefit of in writer's cramp.

In order to explore the pathophysiological basis of a new rehabilitation therapy in writer's cramp (WC), healthy controls, untreated WC patients and WC patients who recovered a legible handwriting after rehabilitation were explored using magnetoencephalography, and the somatosensory evoked fields of fingers I, II, III and V in the sensory cortex were studied. In the cortex controlling the dystonic limb, the size of the hand representation in the trained patients was similar to that of healthy controls, and significantly different from that of untrained patients. Trained patients exhibited 'super-normal' reorganisation of the finger maps. In the cortex controlling the non-dystonic limb, there was little difference between trained and untrained patients, and the hand representation was enlarged and disorganised. The authors hypothesise that prolonged tailored rehabilitation in WC may induce long-term plasticity phenomena, lateralised to the cortex controlling the dystonic hand.

The celebrated écorchés of honoré Fragonard, part 2: The details of the technique used by Fragonard.

It is remarkable that the famous écorchés of Honoré Fragonard have survived the centuries to reach us today. Studies carried out by several teams have established details of the technique used by Fragonard that help to explain their longevity. The injection of the vessels was achieved by means of a mixture of mutton tallow and pine resin diluted in essence of turpentine and essential oils. This gave Fragonard a very high success rate. Above all, he did not add pigments to his mixture while injecting the veins, and this facilitated the procedure. The vessels were painted after preservation to give them the vivid colors that we can still see today. Another detail that explains their exceptional conservation is that the varnish used by Fragonard was composed of Venice turpentine, made from larch resin and known to repel insects.

Kinetic 12C/13C isotope fractionation by invertase: evidence for a small in vitro isotope effect and comparison of two techniques for the isotopic analysis of carbohydrates.

The natural (13)C/(12)C isotope composition (delta(13)C) of plants and organic compounds within plant organs is a powerful tool to understand carbon allocation patterns and the regulation of photosynthetic or respiratory metabolism. However, many enzymatic fractionations are currently unknown, thus impeding our understanding of carbon trafficking pathways within plant cells. One of them is the (12)C/(13)C isotope effect associated with invertases (EC 3.2.1.26) that are cornerstone enzymes for Suc metabolism and translocation in plants. Another conundrum of isotopic plant biology is the need to measure accurately the specific delta(13)C of individual carbohydrates. Here, we examined two complementary methods for measuring the delta(13)C value of sucrose, glucose and fructose, that is, off-line high-performance liquid chromatography (HPLC) purification followed by elemental analysis and isotope ratio mass spectrometry (EA-IRMS) analysis, and gas chromatography-combustion (GC-C)-IRMS. We also used these methods to determine the in vitro (12)C/(13)C isotope effect associated with the yeast invertase. Our results show that, although providing more variable values than HPLC approximately EA-IRMS, and being sensitive to derivatization conditions, the GC-C-IRMS method gives reliable results. When applied to the invertase reaction, both methods indicate that the (12)C/(13)C isotope effect is rather small and it is not affected by the use of heavy water (D(2)O).