Does idiopathic congenital talipes equinovarus have an impact on attainment of developmental milestones? A multicentre international study.

Purpose: The Ponseti method is a well-established approach to treating clubfoot. Potentially, both the underlying pathology and adherence to post-correction bracing can affect lower limb function and age of independent standing and walking. This cohort study investigates the age at which infants with idiopathic clubfoot treated using the Ponseti method achieved three selected developmental milestones and whether or not this correlated with treatment compliance. Methods: A prospectively collected database from four centres was visited. Inclusion criteria were patients with idiopathic clubfoot with no comorbidities or prior treatment. Age at attainment of independent standing, walking, nocturnal continence was compared across three groups: I) congenital talipes equinovarus (CTEV) children compliant with treatment; II) CTEV children non-compliant with treatment; and III) typically-developed siblings. Minimum follow-up was five years. Results: In all, 130 patients (198 feet) fitted the inclusion criteria: 43:87 (F:M). Standing was achieved by a mean 12.0 months in group I (sd 2.50); 12.0 months (sd 2.0) in II and ten months (sd 3.0) in III. Walking was achieved by a mean 15 months (sd 4.0) in group I, 14 months (sd 1.75) in II and 12 months (sd 3) in III, respectively. Both the compliant and non-compliant CTEV children were significantly slower at achieving standing and walking compared to sibling controls (p < 0.0001). There was no significant difference between age of nocturnal continence between the three groups. Conclusion: Infants with idiopathic clubfoot treated according to the Ponseti method achieve independent standing and walking approximately two months later than their typically-developed siblings. The delay is not related to the use of the foot abduction brace. Level of evidence: III

The ocean's role in polar climate change: asymmetric Arctic and Antarctic responses to greenhouse gas and ozone forcing

In recent decades, the Arctic has been warming and sea ice disappearing. By contrast, the Southern Ocean around Antarctica has been (mainly) cooling and sea-ice extent growing. We argue here that interhemispheric asymmetries in the mean ocean circulation, with sinking in the northern North Atlantic and upwelling around Antarctica, strongly influence the sea-surface temperature (SST) response to anthropogenic greenhouse gas (GHG) forcing, accelerating warming in the Arctic while delaying it in the Antarctic. Furthermore, while the amplitude of GHG forcing has been similar at the poles, significant ozone depletion only occurs over Antarctica. We suggest that the initial response of SST around Antarctica to ozone depletion is one of cooling and only later adds to the GHG-induced warming trend as upwelling of sub-surface warm water associated with stronger surface westerlies impacts surface properties. We organize our discussion around ‘climate response functions’ (CRFs), i.e. the response of the climate to ‘step’ changes in anthropogenic forcing in which GHG and/or ozone-hole forcing is abruptly turned on and the transient response of the climate revealed and studied. Convolutions of known or postulated GHG and ozone-hole forcing functions with their respective CRFs then yield the transient forced SST response (implied by linear response theory), providing a context for discussion of the differing warming/cooling trends in the Arctic and Antarctic. We speculate that the period through which we are now passing may be one in which the delayed warming of SST associated with GHG forcing around Antarctica is largely cancelled by the cooling effects associated with the ozone hole. By mid-century, however, ozone-hole effects may instead be adding to GHG warming around Antarctica but with diminished amplitude as the ozone hole heals. The Arctic, meanwhile, responding to GHG forcing but in a manner amplified by ocean heat transport, may continue to warm at an accelerating rate

Two-dimensional flexural ultrasonic phased array for flow measurement

The arrival time detection probability and the measurement range of transit-time ultrasonic flow meters are undermined by the sound drift effect. One solution to this problem is utilizing a phased-array beam steering technique to compensate the bend of the ultrasonic beams. The design, the fabrication and the characterization of two-dimensional flexural ultrasonic phased arrays is investigated in this paper. A meter body with an inner diameter of 146 mmis machined to accommodate the arrays, and flow tests are carried out at different flow rates ranging from 0 to 2500 m3/h. Experimental results indicate that, with the increase of flow rate, the optimum steering angle of arrays increases from 30° to 40.5° when ultrasonic beams travel upstream and decreases from 30° to 22.5° when ultrasonic beams travel downstream. This proof-of-concept design demonstrates the potential of the flexural ultrasonic phased array as an accurate, economic, efficient, and robust solution for gas flow measurement

Impact of sea ice transport on Beaufort Gyre liquid freshwater content

The Arctic Ocean’s Beaufort Gyre (BG) is a wind-driven reservoir of relatively fresh seawater, situated beneath time-mean anticyclonic atmospheric circulation, and is covered by mobile pack ice for most of the year. Liquid freshwater accumulation in and expulsion from this gyre is of critical interest due to its potential to affect the Atlantic meridional overturning circulation and due to the importance of freshwater in modulating vertical fluxes of heat, nutrients and carbon in the ocean, and exchanges of heat and moisture with the atmosphere. Here, we investigate the hypothesis that wind-driven sea ice transport into/from the BG region influences the freshwater content of the gyre and its variability. To test this hypothesis, we use the results of a coordinated climate response function experiment with four ice-ocean models, in combination with targeted experiments using a regional setup of the MITgcm, in which we rotate the surface wind forcing vectors (thereby changing the ageostrophic component of these winds). Our results show that, via an effect on the net thermodynamic growth rate, anomalies in sea ice transport into the BG affect liquid freshwater adjustment. Specifically, increased ice import increases freshwater retention in the gyre, whereas ice export decreases freshwater in the gyre. Our results demonstrate that uncertainty in the ageostrophic component of surface winds, and in the dynamic sea ice response to these winds, has important implications for ice thermodynamics and freshwater. This sensitivity may explain some of the observed inter-model spread in simulations of Beaufort Gyre freshwater and its adjustment in response to wind forcing

The Diagnostic and Therapeutic Role of Leptin and Its Receptor ObR in Glioblastoma Multiforme

Leptin has been recognized as a potential tumor growth promoter in various cancers including cranial tumor pathologies such as pituitary adenomas, meningiomas and gliomas. Despite recent advances in adjunctive therapy and the established surgical resection, chemo- and radiotherapy regimen, glioblastoma multiforme remains a particular diagnostic and therapeutic challenge among the intracranial tumor pathologies, with a poor long-term prognosis. Systemic inflammation and immune-metabolic signaling through diverse pathways are thought to impact the genesis and recurrence of brain tumors, and glioblastoma multiforme in particular. Among the various circulating mediators, leptin has gained especial diagnostic and therapeutic interest, although the precise relationship between leptin and glioblastoma biology remains largely unknown. In this narrative review (MEDLINE/OVID, SCOPUS, PubMed and manual searches of the bibliographies of known primary and review articles), we discuss the current literature using the following search terms: leptin, glioblastoma multiforme, carcinogenesis, immunometabolism, biomarkers, metformin, antidiabetic medication and metabolic disorders. An increasing body of experimental evidence implicates a relationship between the development and maintenance of gliomas (and brain tumors in general) with a dysregulated central and peripheral immune-metabolic network mediated by circulating adipokines, chemokines and cellular components, and in particular the leptin adipokine. In this review, we summarize the current evidence of the role of leptin in glioblastoma pathophysiology. In addition, we describe the status of alternative diagnostic tools and adjunctive therapeutics targeting leptin, leptin-receptors, antidiabetic drugs and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanism of action and the value of immune-metabolism molecular phenotyping (central and peripheral) in order to develop novel adjunctive diagnostics and therapeutics for newly diagnosed and recurrent glioblastoma patients

Synthesis, characterization and complex evaluation of antibacterial activity and cytotoxicity of new arylmethylidene ketones and pyrimidines with camphane skeletons

The synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2- aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM for ketone 39). Compound 35 demonstrated moderate (8.23 μM), but sustainable activity toward a collection of drug-resistant M. tuberculosis strains. Many of the compounds (especially among 2-aminopyridines 42–56) exhibited good to excellent activity against different strains of pathogenic bacteria and fungi (MIC up to 0.60 μM for compound 50), compared with reference antibiotics. Many of the newly designed compounds possess also in vitro cytotoxicity.This study was supported by: Bulgarian National Science Fund- project KP-06-H39/7 and Spanish Ministry of Science, Innovation and Universities- Grant RTI2018-094629-BI00. MEDINA’s authors disclosed the receipt of financial support from Fundación MEDINA, a public-private partnership of Merck Sharp and Dohme de EspañaS.A./Universidad de Granada/Junta de Andalucía

Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors

Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally acting chromatin remodeller. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation