JURNAL AGROTEKNOLOGI
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Studying Müllerian duct anomalies - from cataloguing phenotypes to discovering causation
No full textMüllerian duct anomalies (MDAs) are developmental disorders of the Müllerian duct, the embryonic anlage of most of the female reproductive tract. The prevalence of MDAs is 6.7% in the general female population and 16.7% in women who exhibit recurrent miscarriages. Individuals affected by these anomalies suffer from high rates of infertility, first-trimester pregnancy losses, premature labour, placental retention, foetal growth retardation and foetal malpresentations. The aetiology of MDAs is complex and heterogeneous, displaying a range of clinical pictures that generally lack a direct genotype-phenotype correlation. De novo and familial cases sharing the same genomic lesions have been reported. The familial cases follow an autosomal-dominant inheritance, with reduced penetrance and variable expressivity. Furthermore, few genetic factors and molecular pathways underpinning Müllerian development and dysregulations causing MDAs have been identified. The current knowledge in this field predominantly derives from loss-of-function experiments in mouse and chicken models, as well as from human genetic association studies using traditional approaches, such as microarrays and Sanger sequencing, limiting the discovery of causal factors to few genetic entities from the coding genome. In this Review, we summarise the current state of the field, discuss limitations in the number of studies and patient samples that have stalled progress, and review how the development of new technologies provides a unique opportunity to overcome these limitations. Furthermore, we discuss how these new technologies can improve functional validation of potential causative alterations in MDAs
Proposal for mandatory vaccine-only COVID certification in a Plan B scenario
No full textGovernment consultation
The urgent need to vaccinate dialysis patients against severe acute respiratory syndrome coronavirus 2: a call to action
No full textAggregation in the spotlight
No full textNew findings clarify apparently conflicting results about how molecular agents that preserve protein integrity prevent harmful, dense aggregates from forming
Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions
No full textIon channels are proteins which form gated nanopores in biological membranes. Many channels exhibit hydrophobic gating, whereby functional closure of a pore occurs by local dewetting. The pentameric ligand gated ion channels (pLGICs) provide a biologically important example of hydrophobic gating. Molecular simulation studies comparing additive vs polarizable models indicate predictions of hydrophobic gating are robust to the model employed. However, polarizable models suggest favorable interactions of hydrophobic pore-lining regions with chloride ions, of relevance to both synthetic carriers and channel proteins. Electrowetting of a closed pLGIC hydrophobic gate requires too high a voltage to occur physiologically but may inform designs for switchable nanopores. Global analysis of ∼200 channels yields a simple heuristic for structure-based prediction of (closed) hydrophobic gates. Simulation-based analysis is shown to provide an aid to interpretation of functional states of new channel structures. These studies indicate the importance of understanding the behavior of water and ions within the nanoconfined environment presented by ion channels
Biological therapies for asthma
No full textFive to 10% of asthma patients remain symptomatic and/or have asthma attacks despite adequate inhaled and systemic therapy. Eosinophilic, type 2 airway inflammation is seen in half of these patients with severe asthma. There is now convincing evidence that type 2 inflammation drives susceptibility to asthma attacks and is associated with a good response to biological therapies. Monoclonal antibodies targeting immunoglobulin E, interleukin (IL)-5 and IL-4/13 now have established efficacy in severe type 2 asthma. Novel alarmin-blocking and crystal-dissolving therapies are promising. Prescribing biologics, weaning steroids and treating subsequent exacerbations are rapidly evolving clinical challenges
Supraspinal effects of dorsal root ganglion stimulation in chronic pain patients
No full textObjectives: Dorsal root ganglion stimulation (DRGS) has become a popular neuromodulatory treatment for neuropathic pain. We used magnetoencephalography (MEG) to investigate potential biomarkers of pain and pain relief, based on the differences in power spectral density (PSD) during varying degrees of pain and how these oscillations change during DRGS-mediated pain relief.
Materials and Methods: Thirteen chronic pain patients with implanted dorsal root ganglion stimulators were included in the MEG analysis. MEG Recordings were performed at rest while the stimulator was turned ON or OFF. Numerical rating scale (NRS) scores were also recorded before and after DRGS was turned OFF and ON. Power spectral and source localization analyses were then performed on preprocessed MEG recordings.
Results: With DRGS-OFF, patients in severe pain had significantly increased cortical theta (4–7 Hz) power and decreased cortical alpha (7–13 Hz) power compared to patients reporting less pain. This shift in power toward lower frequencies was contrasted by a shift toward the higher frequency power spectrum (low beta 13–20 Hz activity) during DRGS-mediated pain relief. A significant correlation was found between the increase in low beta activity and the degree of reported pain relief.
Conclusion: Our results demonstrate increased low-frequency power spectral activity in chronic pain patients in the absence of stimulation which shifts toward higher frequency power spectrum activity in response to therapeutic DRGS. These cortical changes in response to DRGS provide support for the use of neuroimaging in the search for potential biomarkers of pain
Impact of delays to incubation and storage temperature on blood culture results: a multi-centre study
No full textBackground
Blood cultures are one of the most important tests performed by microbiology laboratories. Many hospitals, particularly in low and middle-income countries, lack either microbiology services or staff to provide 24 h services resulting in delays to blood culture incubation. There is insufficient guidance on how to transport/store blood cultures if delays before incubation are unavoidable, particularly if ambient temperatures are high. This study set out to address this knowledge gap.
Methods
In three South East Asian countries, four different blood culture systems (two manual and two automated) were used to test blood cultures spiked with five common bacterial pathogens. Prior to incubation the spiked blood culture bottles were stored at different temperatures (25 °C, in a cool-box at ambient temperature, or at 40 °C) for different lengths of time (0 h, 6 h, 12 h or 24 h). The impacts of these different storage conditions on positive blood culture yield and on time to positivity were examined.
Results
There was no significant loss in yield when blood cultures were stored
Conclusion
Blood cultures should be incubated with minimal delay to maximize pathogen recovery and timely result reporting, however, this study provides some reassurance that unavoidable delays can be managed to minimize negative impacts. If delays to incubation ≥ 12 h are unavoidable, transportation at a temperature not exceeding 25 °C, and blind sub-cultures prior to incubation should be considered
