Clinical utility of repeat fetal echocardiography in congenital heart disease.

OBJECTIVES: To investigate the utility of repeat fetal echocardiography (FE) following a diagnosis of structural congenital heart disease (CHD) on the initial FE. We evaluated how often changes in management and counseling occurred based on subsequent FE findings and sought to determine which types of CHD were more likely to have changes in management and/or counseling based on repeat FE. METHODS: This was a retrospective review of all patients who presented to our center between January 2012 and January 2019 and who had more than one FE performed for structural CHD. We reviewed consultation notes to determine whether management or counseling had changed based on FE findings at follow-up visits. Management variables included a change in location or mode of delivery, plan for atrial septostomy, initiation of prostaglandin infusion, umbilical line placement and planned admission location (nursery vs neonatal intensive care unit). We defined a counseling change as any of the above changes in management as well as any meaningful refinements in the cardiac diagnosis that led to a change in the overall prognosis or future management. Initial diagnoses were grouped into anatomically/hemodynamically relevant subgroups. Fisher's exact test was used to assess the relationship between the initial diagnosis and changes in management. Post-hoc pairwise comparisons were performed using Dunnett's test. RESULTS: Between January 2012 and January 2019, 267 patients underwent 534 follow-up FE assessments performed for structural CHD. Management change based on repeat FE occurred in 41/267 (15.4%) cases. A change in management was associated with the diagnosis made at the initial visit (P < 0.001). The proportion of cases with a management change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (4/11 (36.4%)), followed by balanced atrioventricular canal (AVC) defect (5/17 (29.4%)) and left ventricular outflow tract obstruction/aortic valve abnormality or coarctation/interrupted aortic arch (19/68 (27.9%)). No management change occurred in fetuses diagnosed with isolated ventricular septal defect (VSD), truncus arteriosus, pulmonary vein anomaly or isolated arch sidedness/branching abnormality. Compared to those with a VSD, management was significantly more likely to be changed in fetuses with a balanced AVC defect (P = 0.025) and left heart lesions (P = 0.002). Right heart lesions showed a trend towards an increased incidence of management change (P = 0.05). A counseling change based on repeat FE occurred in 108/267 (40.4%) cases. The proportion of cases with a counseling change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (8/11 (72.7%)) and hypoplastic left heart syndrome/critical aortic stenosis (5/9 (55.6%)). CONCLUSIONS: The clinical utility of follow-up FE is associated with the type of CHD diagnosed. Follow-up FE led to changes in management in several types of CHD, most commonly in cases with an initial diagnosis of right and left outflow obstructive lesions and balanced AVC defect. When developing programmatic protocols for the frequency of FE assessments, the type of CHD should be a major determinant, but additional studies are required to reach a consensus on how often serial FE should be performed for each type of CHD. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

The mammalian brain under domestication: Discovering patterns after a century of old and new analyses.

Comparisons of wild and domestic populations have established brain reduction as one of the most consistent patterns correlated with domestication. Over a century of scholarly work has been devoted to this subject, and yet, new data continue to foster its debate. Current arguments, both for and against the validity of brain reduction occurring in domestic taxa, have repeatedly cited a small set of reviews on this subject. The original works, their sampling, methodological details, and nuances of results that would be key to establishing validity, particularly in light of new data, have not been investigated. To facilitate and encourage a more informed discussion, we present a comprehensive review of original brain reduction literature for four mammalian clades: Artiodactyla, Perissodactyla, Carnivora, and Glires. Among these are studies that generated the most cited brain reduction values in modern domestication literature. In doing so, we provide a fairer stage for the critique of traits associated with domestication. We conclude that while brain reduction magnitudes may contain error, empirical data collectively support the reduction in brain size and cranial capacity for domestic forms.

Flashbulb memory recall in healthy adults - a functional magnetic resonance imaging study.

The present study investigated neural activations related to flashbulb memory (FM) recall and examined whether the amygdala and hippocampus are involved in FM recall. 20 healthy adults completed a block design with an FM-condition, where the reception events for a number of potential FM events had to be recalled, and a control condition (FMC) comprising reception events lacking FM characteristics. A definition naming task was used as an implicit baseline. The individual emotional reaction to the FM events (EMO) and self-rated retrieval success were included in the SPM model as modulating parameters. The main contrast of interest were FM > FMC and activations associated with EMO. ROI-analyses on mesiotemporal regions were performed. FM > FMC yielded activations in line with the autobiographical memory network, with mostly left sided-activations. EMO was associated with a more bilateral activation pattern. ROI-analysis revealed activations for EMO in the right amygdala and HATA. FM > FMC was associated with right hippocampal activations. The present findings are compatible with previous research into autobiographical memory, but also show activations for FM recall different from ordinary, not highly emotional autobiographical memories, as EMO is associated with a more bilateral network. Moreover, the amygdala seems to be involved in FM recall.

Psychological factors outmatched morphological markers in predicting limitations in activities of daily living and participation in patients with lumbar stenosis.

BACKGROUND: Recent demographic changes have led to a large population of older adults, many of whom experience degenerative disc diseases. Degenerative lumbar spinal stenosis (DLSS) is associated with considerable discomfort and limitations in activities of daily living (ADL). Symptomatic DLSS is one of the most frequent indications for spinal surgery. The aim of this study was to identify sociodemographic variables, morphological markers, depression as well as fear of movement that predict ADL performance and participation in social life in patients with DLSS. METHODS: Sixty-seven patients with DLSS (mean age 62.5 years [11.7], 50.7% females) participated in the study. Predictor variables were age, gender, duration of disease, three morphological markers (severity of the lumbar stenosis, the number of affected segments and presence of spondylolisthesis) as well as self-reported depression and fear of movement. Dependent variables were pain interference with the performance of ADLs, ADLs and participation in social life. Correlations between predictor and dependent variables were calculated before stepwise, linear regression analyses. Only significant correlations were included in the linear regression analyses. RESULTS: Variance explained by the predictor variables ranged between 12% (R2 = .12; pain interference-physical) and 40% (R2 = .40; ADL requiring lower extremity functioning; participation). Depression and fear of movement were the most powerful predictors for all dependent variables. Among the morphological markers only stenosis severity contributed to the prediction of ADLs requiring lower extremity functioning. CONCLUSION: Depression and fear of movement were more important predictors of the execution of ADLs and participation in social life compared to morphological markers. Elevated depressive symptoms and fear of movement might indicate limited adaptation and coping regarding the disease and its consequences. Early monitoring of these predictors should therefore be conducted in every spine centre. Future studies should investigate whether psychological screening or a preoperative psychological consultation helps to avoid operations and enables better patient outcomes.

How to tackle the molecular species inventory for an industrialized nation-lessons from the first phase of the German Barcode of Life initiative GBOL (2012-2015).

Biodiversity loss is mainly driven by human activity. While concern grows over the fate of hot spots of biodiversity, contemporary species losses still prevail in industrialized nations. Therefore, strategies were formulated to halt or reverse the loss, driven by evidence for its value for ecosystem services. Maintenance of the latter through conservation depends on correctly identified species. To this aim, the German Federal Ministry of Education and Research is funding the GBOL project, a consortium of natural history collections, botanic gardens, and universities working on a barcode reference database for the country's fauna and flora. Several noticeable findings could be useful for future campaigns: (i) validating taxon lists to serve as a taxonomic backbone is time-consuming, but without alternative; (ii) offering financial incentives to taxonomic experts, often citizen scientists, is indispensable; (iii) completion of the libraries for widespread species enables analyses of environmental samples, but the process may not hold pace with technological advancements; (iv) discoveries of new species are among the best stories for the media; (v) a commitment to common data standards and repositories is needed, as well as transboundary cooperation between nations; (vi) after validation, all data should be published online via the BOLD to make them searchable for external users and to allow cross-checking with data from other countries.

Combining geometric morphometrics with molecular genetics to investigate a putative hybrid complex: a case study with barbels Barbus spp. (Teleostei: Cyprinidae).

This integrative study examined the morphological and genetic affinities of three endemic barbel species from Italy (brook barbel Barbus caninus, Italian barbel Barbus plebejus and horse barbel Barbus tyberinus) and of putative hybrid specimens to their species of origin. Two of the species frequently occur together with the non-native barbel Barbus barbus. DNA barcoding indicates that mitochondrial (mt) haplotypes often do not match the species expected from morphology. Linear distance measurements and meristics are not informative for discrimination of the species and putative hybrids, but a discriminant analysis of principal components (DAPC) of geometric landmark data produces reassignments largely in congruence with mt and nuclear genetic data. Cyto-nuclear conflicts confirm the presence of hybridization in B. plebejus and B. tyberinus and identify additional introgressed specimens. A comparison between mixed genotypes and their morphology-based assignment reveals no predictable pattern. The finding that most individuals of the morphologically similar B. plebejus and B. tyberinus have very high assignment probabilities to their respective species suggests that the presented approach may serve as a valuable tool to distinguish morphologically very similar taxa.

First record of second-generation facultative parthenogenesis in a vertebrate species, the whitespotted bambooshark Chiloscyllium plagiosum.

In this study, two parthenogenetic events within a family of the whitespotted bambooshark Chiloscyllium plagiosum are reported. A captive female produced multiple parthenogens. Unexpectedly, a single specimen of a total of nine parthenogens displayed external claspers characterizing the male sex in chondrichthyans. Upon dissection, internal sexual organs of this specimen were malformed or absent; however, the presence of claspers in this study challenges the as yet assumed sex determination system in this shark species. Even more remarkable was that one of the female parthenogens reproduced asexually again producing viable offspring. As far as is known, this is the first genetically confirmed evidence for second-generation facultative parthenogenesis in vertebrates. These results support the evolutionary significance of parthenogenesis as an alternative to sexual reproduction.

Heterochrony and post-natal growth in mammals--an examination of growth plates in limbs.

Mammals display a broad spectrum of limb specializations coupled with different locomotor strategies and habitat occupation. This anatomical diversity reflects different patterns of development and growth, including the timing of epiphyseal growth plate closure in the long bones of the skeleton. We investigated the sequence of union in 15 growth plates in the limbs of about 400 specimens, representing 58 mammalian species: 34 placentals, 23 marsupials and one monotreme. We found a common general pattern of growth plate closure sequence, but one that is universal neither between species nor in higher-order taxa. Locomotor habitat has no detectable correlation with the growth plate closure sequence, but observed patterns indicate that growth plate closure sequence is determined more strongly through phylogenetic factors. For example, the girdle elements (acetabulum and coracoid process) always ossify first in marsupials, whereas the distal humerus is fused before the girdle elements in some placentals. We also found that heterochronic shifts (changes in timing) in the growth plate closure sequence of marsupials occur with a higher rate than in placentals. This presents a contrast with the more limited variation in timing and morphospace occupation typical for marsupial development. Moreover, unlike placentals, marsupials maintain many epiphyses separated throughout life. However, as complete union of all epiphyseal growth plates is recorded in monotremes, the marsupial condition might represent the derived state.

Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5).

AIMS: AWARD-5 was an adaptive, seamless, double-blind study comparing dulaglutide, a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist, with placebo at 26 weeks and sitagliptin up to 104 weeks. The study also included a dose-finding portion whose results are presented here. METHODS: Type 2 diabetes (T2D) patients on metformin were randomized 3 : 1 : 1 to seven dulaglutide doses, sitagliptin (100 mg), or placebo. A Bayesian algorithm was used for randomization and dose selection. Patients were adaptively randomized to dulaglutide doses using available data on the basis of a clinical utility index (CUI) of glycosylated haemoglobin A1c (HbA1c) versus sitagliptin at 52 weeks and weight, pulse rate (PR) and diastolic blood pressure (DBP) versus placebo at 26 weeks. The algorithm randomly assigned patients until two doses were selected. RESULTS: Dulaglutide 1.5 mg was determined to be the optimal dose. Dulaglutide 0.75 mg met criteria for the second dose. Dulaglutide 1.5 mg showed the greatest Bayesian mean change from baseline (95% credible interval) in HbA1c versus sitagliptin at 52 weeks -0.63 (-0.98 to -0.20)%. Dulaglutide 2.0 mg showed the greatest placebo-adjusted mean change in weight [-1.99 (-2.88 to -1.20) kg] and in PR [0.78 (-2.10 to 3.80) bpm]. Dulaglutide 1.5 mg showed the greatest placebo-adjusted mean change in DBP [-0.62 (-3.40 to 2.30) mmHg]. CONCLUSIONS: The Bayesian algorithm allowed for an efficient exploration of a large number of doses and selected dulaglutide doses of 1.5 and 0.75 mg for further investigation in this trial.

Cranial form differences in goats by breed and domestic status.

Domestic goats (Capra hircus) are globally represented by over 300 breeds, making them a useful model for investigating patterns of morphological change related to domestication. However, they have been little studied, likely due to their poor representation in museum collections and the difficulty in obtaining truly wild goat (Capra aegagrus, the bezoar) samples. Similar studies on other species reveal that domestication correlates with craniofacial alterations in domestics, which are non-uniform and often species-specific. Here, we use three-dimensional geometric morphometric methods (3DGMM) to describe and quantify cranial shape variation in wild (n = 21) versus domestic (n = 54) goats. We find that mean cranial shapes differ significantly between wild and domestic goats as well as between certain breeds. The detected differences are lower in magnitude than those reported for other domestic groups, possibly explained by the fewer directions of artificial selection in goat breeding, and their low global genetic diversity compared to other livestock. We also find tooth-row length reduction in the domestics, suggestive of rostral shortening-a prediction of the "domestication syndrome" (DS). The goat model thus expands the array-and combinations of-morphological changes observed under domestication, notably detecting alterations to the calvarium form which could be related to the ~ 15% brain size reduction previously reported for domestic compared to wild goats. The global success of domestic goats is due more to their ability to survive in a variety of harsh environments than to systematized human management. Nonetheless, their domestication has resulted in a clear disruption from the wild cranial form, suggesting that even low-intensity selection can lead to significant morphological changes under domestication.

Cytotoxicity and mycotoxin production of shellfish-derived Penicillium spp., a risk for shellfish consumers.

In order to assess the putative toxigenic risk associated with the presence of fungal strains in shellfish-farming areas, Penicillium strains were isolated from bivalve molluscs and from the surrounding environment, and the influence of the sample origin on the cytotoxicity of the extracts was evaluated. Extracts obtained from shellfish-derived Penicillia exhibited higher cytotoxicity than the others. Ten of these strains were grown on various media including a medium based on mussel extract (Mytilus edulis), mussel flesh-based medium (MES), to study the influence of the mussel flesh on the production of cytotoxic compounds. The MES host-derived medium was created substituting the yeast extract of YES medium by an aqueous extract of mussel tissues, with other constituent identical to YES medium. When shellfish-derived strains of fungi were grown on MES medium, extracts were found to be more cytotoxic than on the YES medium for some of the strains. HPLC-UV/DAD-MS/MS dereplication of extracts from Penicillium marinum and P. restrictum strains grown on MES medium showed the enhancement of the production of some cytotoxic compounds. The mycotoxin patulin was detected in some P. antarcticum extracts, and its presence seemed to be related to their cytotoxicity. Thus, the enhancement of the toxicity of extracts obtained from shellfish-derived Penicillium strains grown on a host-derived medium, and the production of metabolites such as patulin suggests that a survey of mycotoxins in edible shellfish should be considered.

Red blood cells in type 1 diabetes and multiple sclerosis and technologies to measure their emerging roles.

Autoimmune diseases affect over 40 million people in the United States. The cause of most autoimmune diseases is unknown; therefore, most therapies focus on treating the symptoms. This review will focus on the autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis (MS) and the emerging roles of red blood cells (RBCs) in the mechanisms and treatment of T1D and MS. An understanding of the role of the RBC in human health is increasing, especially with respect to its role in the regulation of vascular caliber and vessel dilation. The RBC is known to participate in the regulation of blood flow through the release of key signaling molecules, such as adenosine triphosphate (ATP) and the potent vasodilator nitric oxide (NO). However, while these RBC-derived molecules are known to be determinants of blood flow in vivo, disruptions in their concentrations in the circulation are often measured in common autoimmune diseases. Chemical and physical properties of the RBC may play a role in autoimmune disease onset, especially T1D and MS, and complications associated with downstream extracellular levels of ATP and NO. Finally, both ATP and NO are highly reactive molecules in the circulation. Coupled with the challenging matrix posed by the bloodstream, the measurement of these two species is difficult, thus prompting an appraisal of recent and novel methods to quantitatively determining these potential early indicators of immune response.

Interferon-ß Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disease characterized by damage to the myelin sheath surrounding axons in the central nervous system. While the exact mechanism of this destruction is unknown, excess nitric oxide (NO) and adenosine triphosphate (ATP) have been measured in tissues and fluids obtained from people with MS. Here, incubation of interferon-beta (IFN-ß), an MS drug with an unknown mechanism of action, with red blood cells (RBCs) obtained from people with MS provide evidence of a potential hypermetabolic state in the MS RBC that is decreased with IFN-ß intervention. Specifically, binding of all three components of an albumin/C-peptide/Zn2+ complex to MS RBCs was significantly increased in comparison to control RBCs. For example, the binding of C-peptide to MS RBCs was significantly increased (3.4 ± 0.1 nM) compared to control RBCs (1.6 ± 0.2 nM). However, C-peptide binding to MS RBCs was reduced to a value (1.6 ± 0.3 nM) statistically equal to that of control RBCs in the presence of 2 nM IFN-ß. Similar trends were measured for albumin and Zn2+ binding to RBCs when in the presence of IFN-ß. RBC function was also affected by incubation of cells with IFN-ß. Specifically, RBC-derived ATP and measurable membrane GLUT1 were both significantly decreased (56 and 24%, respectively) in the presence of IFN-ß. Collectively, our results suggest that IFN-ß inhibits albumin binding to the RBC, thereby reducing its ability to deliver ligands such as C-peptide and Zn2+ to the cell and normalizing the basal hypermetabolic state.

Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy.

Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

Exceptional Changes in Skeletal Anatomy under Domestication: The Case of Brachycephaly.

"Brachycephaly" is generally considered a phenotype in which the facial part of the head is pronouncedly shortened. While brachycephaly is characteristic for some domestic varieties and breeds (e.g., Bulldog, Persian cat, Niata cattle, Anglo-Nubian goat, Middle White pig), this phenotype can also be considered pathological. Despite the superficially similar appearance of "brachycephaly" in such varieties and breeds, closer examination reveals that "brachycephaly" includes a variety of different cranial modifications with likely different genetic and developmental underpinnings and related with specific breed histories. We review the various definitions and characteristics associated with brachycephaly in different domesticated species. We discern different types of brachycephaly ("bulldog-type," "katantognathic," and "allometric" brachycephaly) and discuss morphological conditions related to brachycephaly, including diseases (e.g., brachycephalic airway obstructive syndrome). Further, we examine the complex underlying genetic and developmental processes and the culturally and developmentally related reasons why brachycephalic varieties may or may not be prevalent in certain domesticated species. Knowledge on patterns and mechanisms associated with brachycephaly is relevant for domestication research, veterinary and human medicine, as well as evolutionary biology, and highlights the profound influence of artificial selection by humans on animal morphology, evolution, and welfare.

La braquicefalia generalmente se considera un fenotipo en el que el cráneo, específicamente el hocico, es notablemente acortado. Mientras que la braquicefalia es característica de algunas variedades domésticas y razas (p.e. Bulldog, gato persa, vaca ñata, cabra anglo nubiana, cerdo Middle White), también se puede interpretar como un fenotipo patológico. A pesar de que la braquicefalia tiene una apariencia semejante, por lo menos superficial, en estas variedades y razas, al examinarla más en detalle se descubre que la "braquicefalia" incluye una variedad de diferentes modificaciones del cráneo que probablemente tienen diferentes subyacentes genéticos y de desarrollo y que están relacionados con la historia de la raza. Revisamos las diferentes definiciones y propiedades relacionadas con la braquicefalia en varias especies domésticas. Describimos diferentes tipos de braquicefalia (tipo bulldog, "katantognático" y braquicefalia alométrica) y analizamos condiciones morfológicas relacionadas con la braquicefalia incluyendo enfermedades (p.e. síndrome obstructivo respiratorio). Además, examinamos los complejos procesos genéticos y de desarrollo subyacentes y los motivos culturales y de desarrollo por las que variedades braquicéfalas pueden ser más o menos prevalentes en ciertas especies domésticas. El conocimiento de patrones y mecanismos asociados a la braquicefalia son relevantes para la investigación sobre la domesticación, medicina veterinaria y humana, así como para la biología evolutiva y destaca la profunda influencia de la selección artificial sobre la morfología y bienestar de los animales y su evolución.

A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells.

People with type 1 diabetes (T1D) require exogenous administration of insulin, which stimulates the translocation of the GLUT4 glucose transporter to cell membranes. However, most bloodstream cells contain GLUT1 and are not directly affected by insulin. Here, we report that C-peptide, the 31-amino acid peptide secreted in equal amounts with insulin in vivo, is part of a 3-component complex that affects red blood cell (RBC) membranes. Multiple techniques were used to demonstrate saturable and specific C-peptide binding to RBCs when delivered as part of a complex with albumin. Importantly, when the complex also included Zn2+, a significant increase in cell membrane GLUT1 was measured, thus providing a cellular effect similar to insulin, but on a transporter on which insulin has no effect.

Acute effects of bi-hemispheric transcranial direct current stimulation on the neuromuscular function of patients with chronic stroke: A randomized controlled study.

BACKGROUND: Muscle weakness in patients with chronic stroke is due to neuromuscular disorders such as muscle atrophy, loss of voluntary activation or weak muscle contractile properties which are majored by the imbalance of interhemispheric inhibition following stroke. In patients with chronic stroke, unilateral transcranial direct current stimulation improved the maximal isometric strength of paretic knee extensors, but bilateral transcranial direct current stimulation failed to improve concentric strength. This study aimed to assess if a bilateral current stimulation improves isometric maximal strength, voluntary activation and contractile properties of knee extensors in patients with chronic stroke. METHODS: Thirteen patients with chronic stroke and eight young healthy individuals participated in this randomized, simple-blinded, crossover study that included two experimental sessions: one with sham bilateral transcranial direct current stimulation and another with effective bilateral transcranial direct current stimulation (20 min, 2 mA). In the stroke patients, the anode was placed over the primary motor cortex of the affected hemisphere and the cathode over the contralateral primary motor cortex. In healthy participants, the brain side targeted by the anode and the cathode was randomly assigned. In each session, participants performed three assessments of strength, voluntary activation and contractile properties: before, during and after effective/sham bilateral transcranial direct current stimulation. FINDINGS: Bilateral transcranial direct current stimulation had no effect on any neuromuscular assessments in both groups (All P values > 0.05, partial eta-squares varied from 0.02 to 0.06). INTERPRETATION: A single session of bilateral transcranial direct current stimulation did not compensate muscular weakness of knee extensors in patients with chronic stroke.

Minimal detectable change of kinematic and spatiotemporal parameters in patients with chronic stroke across three sessions of gait analysis.

Three-dimensional gait analysis is the gold standard for gait-assessment in patients with stroke. This technique is commonly used to assess the effect of treatment on gait parameters. In clinical practice, three gait analyses are usually carried out (baseline, after treatment and follow-up), the objectives were to define the reproducibility and the Minimum Detectable Change (MDC) for gait parameters in stance and swing measured using 3D-gait analysis, and to assess changes in MDC across three repeated 3D-gait analyses. Three gait analyses (V1, V2 and V3) were performed at 7-day intervals in twenty-six patients with chronic stroke. Kinematic data (in the sagittal plane, during swing and stance) and spatiotemporal data were evaluated for the paretic limb. Reliability was tested using repeated measures ANOVA with a Tukey post hoc test, and the MDC values were calculated for each parameter. Only the range of hip motion during swing changed significantly between V1 and V2, but no other kinematic parameters changed. No significant differences were observed for the spatiotemporal parameters. MDC values were always higher during the V1vsV2 comparison for both kinematic and spatiotemporal parameters. This is the first study to evaluate the MDC for kinematic and spatiotemporal parameters during stance and swing. Reliability of kinematic and spatiotemporal data across sessions was very good over the three sessions. MDC values were the lowest between V2 and V3 for most parameters. Use of the MDC will allow clinicians to more accurately determine the effect of treatments.

Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility.

Protein C inhibitor (PCI) is a nonspecific, heparin-binding serpin (serine protease inhibitor) that inactivates many plasmatic and extravascular serine proteases by forming stable 1:1 complexes. Proteases inhibited by PCI include the anticoagulant activated protein C, the plasminogen activator urokinase, and the sperm protease acrosin. In humans PCI circulates as a plasma protein but is also present at high concentrations in organs of the male reproductive tract. The biological role of PCI has not been defined so far. However, the colocalization of high concentrations of PCI together with several of its target proteases in the male reproductive tract suggests a role of PCI in reproduction. We generated mice lacking PCI by homologous recombination. Here we show that PCI(-/-) mice are apparently healthy but that males of this genotype are infertile. Infertility was apparently caused by abnormal spermatogenesis due to destruction of the Sertoli cell barrier, perhaps due to unopposed proteolytic activity. The resulting sperm are malformed and are morphologically similar to abnormal sperm seen in some cases of human male infertility. This animal model might therefore be useful for analyzing the molecular bases of these human conditions.

Digital macro-photogrammetry in orthodontic tooth movement: case report.

Digital macro-photogrammetry (DMP) method was used to assess the 3-dimensional (3D) movement of the canine during retraction with a Hybrid Retractor (HR) spring (Forestadent, Pforzheim, Germany) following extraction of first premolars. Computer images of the canine were generated from multiple synchronous digital photos of a patient taken during clinical follow-ups. Time intervals were recorded from the begining of the treatment before the insertion of the spring (T0), to the last follow-up session of canine retraction (T8). All movements of the canine were calculated from the generated three dimensional co-ordinates (X,Y, & Z). The results indicated that the canine was distalized about 6,78 mm over a period of 258 days. The maximum velocity of the canine movement was found to be approximately 1 mm/month. In conclusion, it was found that DMP can be applied in clinical orthodontics to monitor orthodontic tooth movement. This technique is cost-effective and measurements can be made on site as the use of computers and digital photographs have been incorporated in the majority of orthodontic practices.