Abstract
Purpose
The Ponseti method is widely used in clubfoot treatment. Long-term follow-up shows high patient satisfaction and excellent functional outcomes. Clubfoot tendency to relapse is a ...problem yet to solve. Given the importance of bracing in relapse prevention, we ought to discuss current knowledge and controversies about bracing.
Methods
We describe types of braces used, with its advantages and disadvantages, suggesting bracing schedules and duration. We identify bracing problems and pinpoint strategies to promote adherence to bracing.
Results
When treating a clubfoot by the Ponseti method, the corrected foot should be held in an abducted and dorsiflexed position, in a foot abduction brace (FAB), with two shoes connected by a bar. The brace is applied after the clubfoot has been completely corrected by manipulation, serial casting and possibly Achilles tenotomy. Bracing is recommended until four to five years of age and needs to be fitted to the individual patient, based on age, associated relapse rate and timing when correction was finished. Parental non-adherence to FAB use can affect 34% to 61% of children and results in five- to 17-fold higher odds of relapse. In patients who have recurrent adherence problems, a unilateral lower leg custom-made orthosis can be considered as a salvage option. Healthcare providers must communicate with patients regarding brace wearing, set proper expectations and ensure accurate use.
Conclusion
Bracing is essential for preventing clubfoot relapse. Daily duration and length of bracing required to prevent recurrence is still unknown. Prospective randomized clinical trials may bring important data that will influence clinicians’ and families’ choices regarding bracing.
Level of Evidence
V
Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical ...community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow‐through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium‐catalyzed hydrogenation, iterative Roush crotylations, gold‐catalyzed spiroketalization and a late‐stage cis‐selective reduction.
Rise of the machines: The syntheses of two spirocyclic polyketides, spirangien A methyl ester and spirodienal A, are described. This machine‐assisted approach extends the application of flow chemistry to complex natural product synthesis and includes several flow‐through processes of transformations commonly encountered in total synthesis.
Paclitaxel is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of paclitaxel is based on microtubule stabilization inducing cell-cycle arrest. ...Here, we use several tumor models to show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes antitumor immunity.
, paclitaxel reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel also modulated the tumor-associated macrophage (TAM) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that paclitaxel altered the M2-like signature of TAMs toward an M1-like profile. In mice selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre
/TLR4
), the antitumor effect of paclitaxel was attenuated. Gene expression analysis of tumor samples from patients with ovarian cancer before and after treatment with paclitaxel detected an enrichment of genes linked to the M1 macrophage activation profile (IFNγ-stimulated macrophages). These findings indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4, which might contribute to the antitumor effect of paclitaxel and provide a rationale for new combination regimens comprising paclitaxel and immunotherapies as an anticancer treatment.
This study provides new evidence that the antitumor effect of paclitaxel occurs in part via reactivation of the immune response against cancer, guiding tumor-associated macrophages toward the M1-like antitumor phenotype.
http://cancerres.aacrjournals.org/content/canres/78/20/5891/F1.large.jpg
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Efficient evolution of hydrogen through electrocatalysis at low overpotentials holds tremendous promise for clean energy. Hydrogen evolution can be easily achieved by electrolysis at large potentials ...that can be lowered with expensive platinum-based catalysts. Replacement of Pt with inexpensive, earth-abundant electrocatalysts would be significantly beneficial for clean and efficient hydrogen evolution. To this end, promising results have been reported using 2H (trigonal prismatic) XS₂ (where X = Mo or W) nanoparticles with a high concentration of metallic edges. The key challenges for XS₂ are increasing the number and catalytic activity of active sites. Here we report monolayered nanosheets of chemically exfoliated WS₂ as efficient catalysts for hydrogen evolution with very low overpotentials. Analyses indicate that the enhanced electrocatalytic activity of WS₂ is associated with the high concentration of the strained metallic 1T (octahedral) phase in the as-exfoliated nanosheets. Our results suggest that chemically exfoliated WS₂ nanosheets are interesting catalysts for hydrogen evolution.
Atmospheric modeling of low-gravity (VL-G) young brown dwarfs remains challenging. The presence of very thick clouds is a possible source of this challenge, because of their extremely red ...near-infrared (NIR) spectra, but no cloud models provide a good fit to the data with a radius compatible with the evolutionary models for these objects. We show that cloudless atmospheres assuming a temperature gradient reduction caused by fingering convection provide a very good model to match the observed VL-G NIR spectra. The sequence of extremely red colors in the NIR for atmospheres with effective temperatures from ∼2000 K down to ∼1200 K is very well reproduced with predicted radii typical of young low-gravity objects. Future observations with NIRSPEC and MIRI on the James Webb Space Telescope (JWST) will provide more constraints in the mid-infrared, helping to confirm or refute whether or not the NIR reddening is caused by fingering convection. We suggest that the presence or absence of clouds will be directly determined by the silicate absorption features that can be observed with MIRI. JWST will therefore be able to better characterize the atmosphere of these hot young brown dwarfs and their low-gravity exoplanet analogs.
To evaluate the effect of an intra-articular (IA) administration of triamcinolone hexacetonide, compared with saline.
Forty (N = 40) hip joints were randomly assigned to a treatment group (THG, n = ...20, receiving IA triamcinolone hexacetonide) and a control group (CG, n = 20, receiving IA saline). On treatment day (T0), and at 8, 15, 30, 90 and 180 days post-treatment, weight distribution, joint range of motion, thigh girth, digital thermography, radiographic signs, synovial fluid interleukin-1 and C-reactive protein levels were evaluated. Data from four Clinical Metrology Instruments was also gathered. Results were compared Repeated Measures ANOVA, with a Huynh-Feldt correction, Paired Samples T-Test or Wilcoxon Signed Ranks Test. A Kaplan-Meier test was performed to compare both groups, with p<0.05.
Joints were graded as mild (65%), moderate (20%) and severe (15%). Patients of both sexes, with a mean age of 6.5±2.4 years and bodyweight of 26.7±5.2kg, were included. No differences were found between groups at T0. Comparing THG to CG, weight distribution showed significant improvements in THG from 8 (p = 0.05) up to 90 days (p = 0.01). THG showed lower values during thermographic evaluation in the Lt view (p<0.01). Pain and function scores also improved from 30 to 180 days. Increasing body weight, age, and presence of caudolateral curvilinear osteophyte corresponded to worse response to treatment. Results of the Kaplan Meier test showed significant differences between groups, with THG performing better considering several evaluations and scores.
THG recorded significant improvements in weight-bearing and in with the considered CMIs, particularly pain scores. Lower thermographic values were registered in THG up to the last evaluation day. Age, sex, and radiographic findings did significantly influenced response to treatment.
Mutations in the PTEN-induced kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (PARKIN) genes are associated with familial forms of Parkinson's disease (PD). PINK1, a protein kinase, and ...PARKIN, an E3 ubiquitin ligase, control the specific elimination of dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial network and preserving energy metabolism. PINK1 regulates PARKIN translocation in impaired mitochondria and drives their removal via selective autophagy, a process known as mitophagy. As knowledge obtained using different PINK1 and PARKIN transgenic animal models is being gathered, growing evidence supports the contribution of mitophagy impairment to several human pathologies, including PD and Alzheimer's diseases (AD). Therefore, therapeutic interventions aiming to modulate PINK1/PARKIN signalling might have the potential to treat these diseases. In this review, we will start by discussing how the interplay of PINK1 and PARKIN signalling helps mediate mitochondrial physiology. We will continue by debating the role of mitochondrial dysfunction in disorders such as amyotrophic lateral sclerosis, Alzheimer's, Huntington's and Parkinson's diseases, as well as eye diseases such as age-related macular degeneration and glaucoma, and the causative factors leading to PINK1/PARKIN-mediated neurodegeneration and neuroinflammation. Finally, we will discuss PINK1/PARKIN gene augmentation possibilities with a particular focus on AD, PD and glaucoma.
This study aimed to compare the symmetry of clinical and radiographic signs of right and left pelvic limbs of dogs with bilateral hip osteoarthritis (OA) and evaluate the association of physical ...findings and radiographic abnormalities.
One hundred pelvic limbs of police working dogs with bilateral hip OA were evaluated, following a screening program. Weight distribution, joint range of motion at flexion and extension, thigh girth, and radiographic signs were recorded and compared with the results of the contralateral limb and by breed, age, and sex with the Paired Samples T-Test and Pearson correlation coefficient, with p<0.05.
The sample mean age was 6.5±2.2 years, and the bodyweight of 26.7±5.3kg. No significant differences were observed when comparing weight distribution, joint range of motion, and thigh girth of left and right limbs. Weight distribution and age showed a statistically significant correlation with joint extension. The right limbs showed a significantly higher frequency of circumferential femoral head osteophyte (CFHO) regarding radiographic signs. Limbs with CFHO or caudolateral curvilinear osteophyte had significantly larger joint flexion angle (p = 0.02) and smaller extension angle (p<0.01), respectively, compared to those that did not. Age showed a significant correlation with the presence of several radiographic findings, as did different breeds.
Clinical and radiographic signs occur symmetrically in naturally occurring hip OA in police working dogs. Several correlations were observed between the evaluations performed and differences between breeds, which can be useful in assessing and early diagnosis of hip OA.
Competition is a widespread interaction among carnivores, ultimately manifested through one or more dimensions of the species' ecological niche. One of the most explicit manifestations of competitive ...interactions regards spatial displacement. Its interpretation under a theoretical context provides an important tool to deepen our understanding of biological systems and communities, but also for wildlife management and conservation. We used Bayesian multispecies occupancy models on camera-trapping data from multiple sites in Southwestern Europe (SWE) to investigate competitive interactions within a carnivore guild, and to evaluate how species' ecological traits are shaping coexistence patterns. Seventeen out of 26 pairwise interactions departed from a hypothesis of independent occurrence, with spatial association being twice as frequent as avoidance. Association behaviors were only detected among mesocarnivores, while avoidance mainly involved mesocarnivores avoiding the apex predator (n = 4) and mesocarnivore-only interactions (n = 2). Body mass ratios, defined as the dominant over the subordinate species body mass, revealed an important negative effect (β̂ = −0.38; CI95 = −0.81 to −0.06) on co-occurrence probability, and support that spatially explicit competitive interactions are mostly expressed by larger species able to dominate over smaller ones, with a threshold in body mass ratios of ∼4, above which local-scale intraguild coexistence is unlikely. We found a weak relationship between pairwise trophic niche overlap and the probability of coexistence (β̂ = −0.19; CI95 = −0.58 to 0.21), suggesting that competition for feeding resources may not be a key driver of competition, at least at the scale of our analysis. Despite local-scale avoidance, regional-scale coexistence appears to be maintained by the spatial structuring of the competitive environment. We provide evidence that SWE ecosystems consist of spatially structured competitive environments, and propose that coexistence among near-sized species is likely achieved through the interplay of “facultative” and “behavioral” character displacements. Factors influencing carnivore coexistence likely include context-dependent density and trait-mediated effects, which should be carefully considered for a sound understanding of the mechanisms regulating these communities.
Abstract
The mammalian apical-basal determinant Crumbs homolog-1 (CRB1) plays a crucial role in retinal structure and function by the maintenance of adherens junctions between photoreceptors and ...Müller glial cells. Patients with mutations in the CRB1 gene develop retinal dystrophies, including early-onset retinitis pigmentosa and Leber congenital amaurosis. Previously, we showed that Crb1 knockout mice developed a slow-progressing retinal phenotype at foci in the inferior retina, although specific ablation of Crb2 in immature photoreceptors leads to an early-onset phenotype throughout the retina. Here, we conditionally disrupted one or both alleles of Crb2 in immature photoreceptors, on a genetic background lacking Crb1, and studied the retinal dystrophies thereof. Our data showed that disruption of one allele of Crb2 in immature photoreceptors caused a substantial aggravation of the Crb1 phenotype in the entire inferior retina. The photoreceptor layer showed early-onset progressive thinning limited to the inferior retina, although the superior retina maintained intact. Surprisingly, disruption of both alleles of Crb2 in immature photoreceptors further aggravated the phenotype. Throughout the retina, photoreceptor synapses were disrupted and photoreceptor nuclei intermingled with nuclei of the inner nuclear layer. In the superior retina, the ganglion cell layer appeared thicker because of ectopic nuclei of photoreceptors. In conclusion, the data suggest that CRB2 is required to maintain retinal progenitor and photoreceptor cell adhesion and prevent photoreceptor ingression into the immature inner retina. We hypothesize, from these animal models, that decreased levels of CRB2 in immature photoreceptors adjust retinitis pigmentosa because of the loss of CRB1 into Leber congenital amaurosis phenotype.
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