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1.
New Phytol ; 230(4): 1665-1679, 2021 05.
Article in English | MEDLINE | ID: mdl-33521943

ABSTRACT

Demand for cannabidiol (CBD), the predominant cannabinoid in hemp (Cannabis sativa), has favored cultivars producing unprecedented quantities of CBD. We investigated the ancestry of a new cultivar and cannabinoid synthase genes in relation to cannabinoid inheritance. A nanopore-based assembly anchored to a high-resolution linkage map provided a chromosome-resolved genome for CBDRx, a potent CBD-type cultivar. We measured cannabinoid synthase expression by cDNA sequencing and conducted a population genetic analysis of diverse Cannabis accessions. Quantitative trait locus mapping of cannabinoids in a hemp × marijuana segregating population was also performed. Cannabinoid synthase paralogs are arranged in tandem arrays embedded in long terminal repeat retrotransposons on chromosome 7. Although CBDRx is predominantly of marijuana ancestry, the genome has cannabidiolic acid synthase (CBDAS) introgressed from hemp and lacks a complete sequence for tetrahydrocannabinolic acid synthase (THCAS). Three additional genomes, including one with complete THCAS, confirmed this genomic structure. Only cannabidiolic acid synthase (CBDAS) was expressed in CBD-type Cannabis, while both CBDAS and THCAS were expressed in a cultivar with an intermediate tetrahydrocannabinol (THC) : CBD ratio. Although variation among cannabinoid synthase loci might affect the THC : CBD ratio, variability among cultivars in overall cannabinoid content (potency) was also associated with other chromosomes.


Subject(s)
Cannabidiol , Cannabinoids , Cannabis , Cannabis/genetics , Chromosome Mapping , Dronabinol
2.
Appetite ; 158: 104989, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33075444

ABSTRACT

Healthy infant feeding practices form the basis of healthy eating behaviour later in life. The effect of providing parents with recommendations on textured food introduction between 8 and 15 months on children's experience with and acceptance of textured foods was studied. Sixty parent/child dyads were randomly assigned to a control group (CG) receiving current French recommendations and an intervention group (IG) receiving a brochure with supplementary advice, tips and monthly counselling on food texture introduction. After the intervention, parents completed self-report measures about the introduction of 188 food items, including purees, soft/small pieces, hard/large pieces and double textures. Children's acceptance of eight textured foods was assessed in a laboratory setting. Parents in the IG introduced more soft/small food pieces (P = 0.004) but not more complex textures (P = 0.15). There was no group difference in children acceptance for any of the textured foods offered in the laboratory. Independent of their study group, children's exposure to texture was associated with birth order, self-feeding with fingers, low gagging frequency and seldom use of commercial baby foods. Higher acceptance was associated with higher exposure to food pieces but not to pureed foods (either smooth or rough) and with children's eating behavioural traits (high food enjoyment, high food responsiveness and low food fussiness). This pilot intervention demonstrated that providing information can be effective in promoting the introduction of small and soft food pieces, but the most effective way to influence the introduction of more challenging textures (hard pieces and double texture) is uncertain. Further research should focus on the identification of barriers to complex texture introduction and on how building on this knowledge for a population-based public health intervention.


Subject(s)
Food Preferences , Infant Food , Child , Feeding Behavior , Humans , Infant , Parents , Pilot Projects
3.
Phys Rev Lett ; 120(2): 023901, 2018 Jan 12.
Article in English | MEDLINE | ID: mdl-29376703

ABSTRACT

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

4.
Geophys Res Lett ; 44(19): 10054-10062, 2017 10 16.
Article in English | MEDLINE | ID: mdl-29200535

ABSTRACT

The effect of the Madden-Julian Oscillation (MJO) on the Northern Hemisphere wintertime stratospheric polar vortex in the period preceding stratospheric sudden warmings is evaluated in operational subseasonal forecasting models. Reforecasts which simulate stronger MJO-related convection in the Tropical West Pacific also simulate enhanced heat flux in the lowermost stratosphere and a more realistic vortex evolution. The time scale on which vortex predictability is enhanced lies between 2 and 4 weeks for nearly all cases. Those stratospheric sudden warmings that were preceded by a strong MJO event are more predictable at ∼20 day leads than stratospheric sudden warmings not preceded by a MJO event. Hence, knowledge of the MJO can contribute to enhanced predictability, at least in a probabilistic sense, of the Northern Hemisphere polar stratosphere.

5.
Aging Clin Exp Res ; 29(6): 1201-1209, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28247211

ABSTRACT

BACKGROUND: Gait patterns of healthy aging are needed to allow a comparison with pathological situations. However, little data is available. OBJECTIVE: To present gait pattern of healthy older specially selected to be "healthy walkers". METHOD: Fifty-seven older people benefited from a geriatric assessment including clinical and functional evaluations to include only those without gait disorders. Gait data were simultaneously recorded using a tri-axial accelerometer placed on the waist and four 3D position markers placed on the feet at the level of the heel and the toe. Volunteers walked at comfortable self-selected speed (CW), fast self-selected speed (FW), and finally in dual task walking condition (DTW). The extracted gait parameters were: gait speed, stride length, stride frequency, regularity and symmetry, swing, stance and double support time and ratio and minimum toe clearance. Gait speed and stride length were normalized to the right leg length. RESULTS: Fifty-seven older people with a mean age of 69.7 ± 4.2 years old (range from 65 to 82 years) were included. Data were analyzed according to the gender and according to the age (<70 or ≥70 years old). After normalization to leg length, the main significant differences were shown for stride length and minimum toe clearance in CW, FW and in DTW that were shorter in women. The regularity in FW was significantly lower among older volunteers. CONCLUSIONS: This work provides a data set considering 14 gait parameters obtained from 57 healthy old people strictly selected and assessed for three walking conditions and shows that GS, SL and MTC have to be related to the gender. The age-related impact on gait performances appears reduced in this cohort.


Subject(s)
Gait/physiology , Geriatric Assessment/methods , Accelerometry/methods , Age Factors , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Foot/physiology , Health Status , Humans , Image Processing, Computer-Assisted/methods , Leg/physiology , Male , Prospective Studies , Reference Values , Sex Factors
6.
Med Teach ; 39(10): 1096-1098, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28749198

ABSTRACT

AIM: Empathy is a core element in the doctor-patient relationship. This study examined whether empathy in medical students can be improved by specific training. METHODS: 158 medical students were randomized into two groups. The intervention group participated in an empathy skills training with simulated patients (SPs). The control group participated in a history course. After the intervention, empathy was assessed by blinded SPs and experts in an Objective Structured Clinical Examination (OSCE). Students also filled out a self-assessment concerning their attitude on empathy (Jefferson Scale of Physician Empathy Student Version, JSPE-S-S). RESULTS AND CONCLUSIONS: Participants of the intervention group showed significantly higher levels of empathy when rated by SPs and experts than the control group. In contrast to that, no significant group differences were observed in self-rated empathy. The results underpin the value of empathy skills trainings in medical school study programs.


Subject(s)
Empathy , Patient Simulation , Physician-Patient Relations , Psychotherapy/education , Students, Medical/psychology , Adult , Female , Humans , Male , Psychiatry/education , Schools, Medical , Self-Assessment
7.
Clin Psychol Psychother ; 24(3): 785-792, 2017 May.
Article in English | MEDLINE | ID: mdl-27699920

ABSTRACT

While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD.


Subject(s)
Cognitive Behavioral Therapy/methods , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/therapy , Self Concept , Adolescent , Adult , Female , Germany , Humans , Male , Middle Aged , Severity of Illness Index , Treatment Outcome , Young Adult
8.
Mol Psychiatry ; 20(4): 459-71, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25070536

ABSTRACT

Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.


Subject(s)
Genetic Therapy , Microcephaly/genetics , Microcephaly/therapy , Neural Stem Cells/physiology , Nuclear Proteins/deficiency , Adenoviridae/genetics , Animals , Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome/metabolism , Apoptosis/genetics , Brain/pathology , Carrier Proteins/genetics , Cell Adhesion Molecules/metabolism , Cell Cycle , Cell Proliferation , DNA-Binding Proteins , Disease Models, Animal , Embryo, Mammalian , Female , Humans , Male , Mice , Mice, Knockout , Microcephaly/pathology , Nestin/genetics , Nestin/metabolism , Neurogenesis , Nuclear Proteins/genetics , Synapsins/genetics , Synapsins/metabolism
9.
Radiologe ; 56(4): 325-37, 2016 Apr.
Article in German | MEDLINE | ID: mdl-27000276

ABSTRACT

Ductal pancreatic adenocarcinoma is by far the most common solid tumor of the pancreas. It has a very poor prognosis, especially in the more advanced stages which are no longer locally confined. Due to mostly unspecific symptoms, imaging is key in the diagnostic process. Because of the widespread use of imaging techniques, incidental findings are to a greater extent discovered in the pancreas, which subsequently entail further work-up. Ductal pancreatic adenocarcinoma can be mimicked by a large number of different lesions, such as anatomical variants, peripancreatic structures and tumors, rarer primary solid pancreatic tumors, cystic tumors, metastases or different variants of pancreatitis. Additionally, a number of precursor lesions can be differentiated. The correct classification is thus important as an early diagnosis of ductal pancreatic adenocarcinoma is relevant for the prognosis and because the possibly avoidable treatment is very invasive. All major imaging techniques are principally suitable for pancreatic imaging. In addition to sonography of the abdomen, usually the baseline diagnostic tool, computed tomography (CT) with its superior spatial resolution, magnetic resonance imaging (MRI) with its good soft tissue differentiation capabilities, possibly in combination with MR cholangiopancreatography (MRCP), endosonography with its extraordinary spatial resolution, conceivably with additional endoscopic retrograde CP or the option of direct biopsy and finally positron emission tomography CT (PET-CT) as a molecular imaging tool are all particularly useful modalities. The various techniques all have its advantages and disadvantages; depending on the individual situation they may need to be combined.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Cholangiopancreatography, Magnetic Resonance/methods , Endosonography/methods , Molecular Imaging/methods , Pancreatic Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Carcinoma, Pancreatic Ductal/pathology , Diagnosis, Differential , Evidence-Based Medicine , Humans , Pancreatic Neoplasms/pathology
10.
Clin Genet ; 88(4): 386-90, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25256757

ABSTRACT

A novel X-linked intellectual disability (XLID) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26-q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X-linked (RBMX) gene at Xq26 in the affected males (n = 7), one carrier female, absent in unaffected males (n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non-coding regions of RBMX; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.


Subject(s)
Exome , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Mental Retardation, X-Linked/genetics , Adolescent , Adult , Aged , DNA Mutational Analysis , Female , Genetic Association Studies , Humans , Male , Middle Aged , Pedigree
11.
Clin Genet ; 87(5): 461-6, 2015 May.
Article in English | MEDLINE | ID: mdl-24805811

ABSTRACT

Alpha-thalassemia intellectual disability, one of the recognizable X-linked disability syndromes, is characterized by short stature, microcephaly, distinctive facies, hypotonic appearance, cardiac and genital anomalies, and marked skewing of X-inactivation in female carriers. With the advent of next generation sequencing, mutations have been identified that result in less severe phenotypes lacking one or more of these phenotypic manifestations. Here we report five unrelated kindreds in which a c.109C>T (p.R37X) mutation segregates with a variable but overall milder phenotype. The distinctive facial appearance of alpha-thalassemia intellectual disability was present in only one of the 18 affected males evaluated beyond the age of puberty, although suggestive facial appearance was present in several during infancy or early childhood. Although the responsible genetic alteration is a nonsense mutation in exon 2 of ATRX, the phenotype appears to be partially rescued by the production of alternative transcripts and/or other molecular mechanisms.


Subject(s)
Alleles , Codon, Nonsense , DNA Helicases/genetics , Mental Retardation, X-Linked/diagnosis , Mental Retardation, X-Linked/genetics , Nuclear Proteins/genetics , Phenotype , alpha-Thalassemia/diagnosis , alpha-Thalassemia/genetics , Adolescent , Child , Child, Preschool , Facies , Female , Genes, X-Linked , Heterozygote , Humans , Infant , Male , Pedigree , X-linked Nuclear Protein , Young Adult
12.
Mol Psychiatry ; 19(3): 294-301, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23439483

ABSTRACT

Many putative genetic factors that confer risk to neurodevelopmental disorders such as autism spectrum disorders (ASDs) and X-linked intellectual disability (XLID), and to neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and schizophrenia (SZ) have been identified in individuals from diverse human populations. Although there is significant aetiological heterogeneity within and between these conditions, recent data show that genetic factors contribute to their comorbidity. Many studies have identified candidate gene associations for these mental health disorders, albeit this is often done in a piecemeal fashion with little regard to the inherent molecular complexity. Here, we sought to abstract relationships from our knowledge of systems level biology to help understand the unique and common genetic drivers of these conditions. We undertook a global and systematic approach to build and integrate available data in gene networks associated with ASDs, XLID, ADHD and SZ. Complex network concepts and computational methods were used to investigate whether candidate genes associated with these conditions were related through mechanisms of gene regulation, functional protein-protein interactions, transcription factor (TF) and microRNA (miRNA) binding sites. Although our analyses show that genetic variations associated with the four disorders can occur in the same molecular pathways and functional domains, including synaptic transmission, there are patterns of variation that define significant differences between disorders. Of particular interest is DNA variations located in intergenic regions that comprise regulatory sites for TFs or miRNA. Our approach provides a hypothetical framework, which will help discovery and analysis of candidate genes associated with neurodevelopmental and neuropsychiatric disorders.


Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Child Development Disorders, Pervasive/genetics , Genetic Predisposition to Disease/genetics , Mental Retardation, X-Linked/genetics , Models, Genetic , Schizophrenia/genetics , Databases, Genetic , Gene Expression Regulation/genetics , Genetic Association Studies/statistics & numerical data , Humans , MicroRNAs/genetics , Transcription Factors/genetics
14.
Appetite ; 84: 280-90, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25453593

ABSTRACT

Breastfeeding (BF) is associated with willingness to accept vegetables. This may be due to the variety of flavours delivered via breast milk. Some mothers add vegetables to milk during complementary feeding (CF) to enhance acceptance. The present study tested a step-by-step exposure to vegetables in milk then rice during CF, on intake and liking of vegetables. Just before CF, enrolled mothers were randomised to an intervention (IG, n = 18; 6 BF) or control group (CG, n = 18; 6 BF). IG infants received 12 daily exposures to vegetable puree added to milk (days 1-12), then 12 × 2 daily exposures to vegetable puree added to rice at home (days 13-24). Plain milk and rice were given to CG. Then both received 11 daily exposures to vegetable puree. Intake was weighed and liking rated on days 25-26 and 33-35 after the start of CF in the laboratory, supplemented by the same data recorded at home. Vegetables were rotated daily (carrots, green beans, spinach, broccoli). Intake, liking and pace of eating were greater for IG than CG infants. Intake and liking of carrots were greater than green beans. However, at 6m then 18m follow up, vegetable (carrot > green beans) but not group differences were observed. Mothers reported appreciation of the structure and guidance of this systematic approach. Early exposure to vegetables in a step-by-step method could be included in CF guidelines and longer term benefits assessed by extending the exposure period.


Subject(s)
Breast Feeding , Diet , Eating , Food Preferences , Infant Food , Infant Nutritional Physiological Phenomena , Vegetables , Adult , Female , Humans , Infant , Male
15.
Eur J Orthop Surg Traumatol ; 25(2): 227-32, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24816824

ABSTRACT

Management of bone loss in revision total hip replacement remains a challenge. To eliminate any immunological or infectious problem and so to try to improve the long-term results obtained with allografts, the authors used synthetic ceramics as bone substitutes since 1995. We reviewed 13 of the patients of our study, we previously reported in 2005 (Schwartz and Bordei in Eur J Orthop Surg Traumatol 15: 191 2005), which was a prospective cohort of thirty-two cases of acetabular revision reconstruction, with a mean follow-up of 14.4 years yet (from 9 to 16 years). Clinical results were assessed according to Oxford scale and Postel and Merle d'Aubigne (PMA) scale. Since 2005, no specific complications were noted. The average PMA functional hip score was 14.9 (vs. 9.2 before revision) at follow-up over 9 years. Nine patients still alive in 2013 were seen again by a surgeon, which was not the operator, with a mean follow-up of 15.3 years: Their Oxford average score was 40.3. Radiological assessment affirmed a good integration of the substitutes in bone without any edging in all cases. A progressive invasion of the ceramics by bone can be seen on the X-ray. We conclude that about 15 years of average delay, which is a significant follow-up in orthopedic surgery, the outcomes without specific complications are satisfactory and allow one to go with these materials in total hip revision surgery.


Subject(s)
Acetabuloplasty/methods , Arthroplasty, Replacement, Hip/adverse effects , Bone Substitutes/therapeutic use , Calcium Phosphates/therapeutic use , Ceramics/therapeutic use , Acetabuloplasty/instrumentation , Aged , Aged, 80 and over , Bone Substitutes/chemistry , Ceramics/chemistry , Female , Follow-Up Studies , Humans , Male , Middle Aged , Reoperation/methods , Time Factors , Treatment Outcome
16.
Eur J Orthop Surg Traumatol ; 25(4): 717-21, 2015 May.
Article in English | MEDLINE | ID: mdl-25534005

ABSTRACT

INTRODUCTION: The shoulder pain has been reported as the third most common site after low back pain and knee pain, mostly caused by impingement and rotator cuff syndromes. Surgery is indicated when non-operative treatment fails and can be open and/or arthroscopic. Are Neer's acromioplasty results still good? Are they modified when it is a professional disease (PD)? If yes is there any explanation? MATERIALS AND METHODS: It is a retrospective hospital-based study, including all cases of Neer's acromioplasty done from 2006 to 2011, by the same senior surgeon for subacromial impingement syndrome (SIS). Medical files were consulted and an auto Disabilities of the Arm, Shoulder and Hand (DASH) score file completed by patients. We compared two groups: "with PD" and "without PD". RESULTS: We had 41 patients (21 males/20 females). Mean age: 54 (34-79) years. The majority was workers those requiring force (29.3 %) or working in abduction situations (7.2 %). The two groups were otherwise comparable (clinical, imaging and surgery findings). Aggressive acromia were found in 15 cases (36.6 %), and there were 19 (46.3 %) rotator cuff perforations. A Neer's acromioplasty and bursectomy was done in all the cases. Eighteen perforations were sutured and one (the largest) was just released. Mean follow-up: 4 (2-9) years. Of the 26 (63.4 %) patients that could return to work, 16 (61.5 %) were not PD. This return was later in the "PD group" (p < 0.05). The DASH score elements in the "without PD" group were better, compared to the PD group: (a) 16 (79.2 %) very good results on the pain against 6 (30 %), (b) 13 (61.9 %) very good results concerning the strength against 3 (15 %), (c) 14 (66.7 %) very good results in the ability to work against 4 (20 %). The DASH global mean score was 35.1 over 100. The global scores for daily life, sport and professional activities were, respectively, 33, 37.8 and 48.2 over 100. In the PD group, the mean DASH score was 53.7 against 17.44 in the non-PD what is more than three times worst. DISCUSSION: Neer's mini-open acromioplasty is still an excellent pain killer operation and should not be abandoned. Very good results on the SIS pain after a mean follow-up of 4 years were observed. Its results are very good in the "without PD" group with 76.19 % of return to previous work after a mean period of 8 months. Earlier return to a new work or to the same work with accommodations is possible. We found no anatomical explanation for the differences between the two groups.


Subject(s)
Acromion/surgery , Occupational Diseases/surgery , Shoulder Impingement Syndrome/surgery , Shoulder Pain/surgery , Activities of Daily Living , Adult , Aged , Bursitis/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Rotator Cuff Injuries , Rupture/surgery , Suture Techniques , Treatment Outcome
17.
Br J Cancer ; 111(4): 726-35, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-25025962

ABSTRACT

BACKGROUND: Over the past years, some members of the family of suppressor of cytokine signalling (SOCS) proteins have emerged as potential tumour suppressors. This study aimed at investigating the clinical significance of SOCS proteins in colorectal carcinoma (CRC). METHODS: We integrated publicly available microarray expression data on CRC in humans, analysed the expression pattern of SOCSs and assessed the predictive power of SOCS2 and SOCS6 for diagnostic purposes by generating receiver operating characteristic curves. Using laser microdissected patient material we assessed SOCS expression on RNA and protein levels as well as their methylation status in an independent CRC patient cohort. Finally, we investigated the prognostic value of SOCS2 and SOCS6. RESULTS: The meta-analysis as well as the independent patient cohort analysis reveal a stage-independent downregulation of SOCS2 and SOCS6 and identify both molecules as diagnostic biomarkers for CRC. We demonstrate a different methylation pattern within the SOCS2 promoter between tumour tissue and normal control tissue in 25% of CRC patients. Furthermore, early CRC stage patients with low expression of SOCS2 display significantly shorter disease-free survival. CONCLUSIONS: Our data offers evidence that SOCS2 and SOCS6 levels are reduced in CRC and may serve as diagnostic biomarkers for CRC patients.


Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Adenocarcinoma/pathology , Adenoma/metabolism , Adenoma/pathology , Adult , Aged , Aged, 80 and over , Base Sequence , Biomarkers, Tumor , Colorectal Neoplasms/pathology , DNA Methylation , Disease-Free Survival , Down-Regulation , Female , Gene Expression , Humans , Male , Middle Aged , Molecular Sequence Data , Neoplasm Staging , Prognosis , Promoter Regions, Genetic , ROC Curve , Suppressor of Cytokine Signaling Proteins/genetics
18.
Eur J Pediatr ; 173(5): 575-82, 2014 May.
Article in English | MEDLINE | ID: mdl-24248522

ABSTRACT

UNLABELLED: Based on recent studies in adult subjects, saliva composition is increasingly considered as a physiological factor contributing to taste sensitivity or acceptance. In order to evaluate a possible link between salivary protein composition and taste acceptance in infants, 73 infants participated longitudinally in taste acceptance tests and donated saliva at the age at 3 and 6 months. Intake ratios, reflecting acceptance of a taste solution relative to water were calculated for the five basic tastes. Salivary proteins were separated by one-dimensional electrophoresis and bands were semi-quantified by image analysis. Partial least square (PLS) regression analyses were performed for each taste at both ages to explain intake ratios by band intensities. Bitterness acceptance in the younger infants was unique in the sense that salivary protein profiles could partly predict bitter taste acceptance. At that age, infants were on average indifferent to the 0.18-M urea solution, but great variability in acceptance was observed. The six bands considered as the best predictors for bitterness acceptance were identified by MALDI-TOF mass spectrometry. Higher abundance of bands containing secretory component, zinc-α-2-glycoprotein and carbonic anhydrase 6 was associated to a lower bitterness acceptance, while higher abundance of bands containing lactoperoxidase, prolactin-inducible protein and S-type cystatins was associated to a higher bitterness acceptance. In a second stage, S-type cystatin abundance was measured by Western blotting in order to tentatively confirm this particular finding in an independent group of 22 infants. Although not reaching statistical significance, probably due to a relatively small sample size, it was again observed that cystatin abundance was higher in infants accepting more readily the bitter solution over water. CONCLUSION: saliva protein composition may contribute to bitter taste acceptance in the younger infants.


Subject(s)
Salivary Proteins and Peptides/physiology , Taste/physiology , Blotting, Western , Citric Acid/pharmacology , Electrophoresis, Polyacrylamide Gel , Female , Humans , Infant , Lactose/pharmacology , Longitudinal Studies , Male , Prospective Studies , Saliva/chemistry , Salivary Proteins and Peptides/analysis , Sodium Chloride/pharmacology , Sodium Glutamate/pharmacology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Taste Threshold/physiology , Urea/pharmacology
19.
J Med Genet ; 50(7): 463-72, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23644449

ABSTRACT

BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.


Subject(s)
Brain Diseases, Metabolic, Inborn/genetics , Creatine/deficiency , Creatine/metabolism , Mental Retardation, X-Linked/genetics , Nerve Tissue Proteins/genetics , Plasma Membrane Neurotransmitter Transport Proteins/deficiency , Adult , Child , Creatine/genetics , Genes, X-Linked , Genetic Testing , Genotype , Humans , Male , Phenotype , Plasma Membrane Neurotransmitter Transport Proteins/genetics , Retrospective Studies
20.
J Bodyw Mov Ther ; 39: 525-530, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38876679

ABSTRACT

The Askling's H-test is considered a useful return to play criterion after a hamstring muscle injury (HMI). However, it assesses only the active and passive flexibility of posterior thigh muscles. This may lead the practitioner to underestimate a compensation or abnormal movement pattern. The aim of this study was to analyze these kinematic aspects and their reliability, and evaluate the hamstring (HM) and gluteus maximus (GM) muscles' activities. Twelve healthy male volunteers were tested during two session of three trials for passive and active tests. Dynamic flexibility (97.2 ± 6.0°) was significantly greater than the passive one (70.5 ± 14.7°) (p < 0.001), and good intra-individual reproductibility for most kinematic characteristics was observed. Biceps Femoris long head, semitendinosus and GM mean activities (20.1 ± 11.2%; 14.3 ± 7.3% and 25.2 ± 22.1%, respectively) were found to be low to moderate, indicating that only a moderate level of activity occurred during the active H-test, in comparison to other movements such as sprinting itself. In addition, the activity of the posterior thigh muscles during the active H-test appeared to be variable among the volunteers. These findings suggest that the H-test should be interpreted on an individual basis rather than relying on general characteristics, and be considered as an intermediate tool before more strenuous activities such as returning to sprint. With this comprehensive approach, clinicians can gain a more accurate understanding of their patients' progress and make more informed decisions about their readiness to return to play.


Subject(s)
Electromyography , Hamstring Muscles , Thigh , Humans , Male , Electromyography/methods , Biomechanical Phenomena/physiology , Hamstring Muscles/physiology , Adult , Thigh/physiology , Young Adult , Range of Motion, Articular/physiology , Muscle, Skeletal/physiology , Reproducibility of Results
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