Nanofiltration membranes have limited ion-ion selectivity in water treatment applications, especially when separating ions with similar size and charge. To achieve greater size-based selectivity in ...nanofiltration, more control of pore structure is required during membrane fabrication. We demonstrate how to tailor membrane pore size and thickness using polyelectrolyte layer-by-layer assembly by alternately applying two strong polyelectrolytes, PDADMAC and PSS, to a polysulfone substrate while systematically controlling the polyelectrolyte and salt concentrations in the deposition solution. Results suggest that increasing polyelectrolyte concentration or salt concentration in the deposition solution increases polyelectrolyte multilayer thickness, but the effects on pore size may be categorized into two distinct regimes. In the first growth regime, increasing polyelectrolyte concentration in the deposition solution led to larger polymer deposition rates and smaller pore sizes. In the second growth regime, increasing polyelectrolyte concentration produced larger pore sizes. We attribute the second regime to less adsorbed polyelectrolyte on the membrane and/or less coiled polymer chains as a result of changing polyelectrolyte-salt interactions. Overall, results show that pore size modification is achievable using layer-by-layer assembly by tuning polyelectrolyte-salt interactions and can be used to study and improve size-based selectivity in membrane separation processes.
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•Tuning pore structure of polyelectrolyte layer-by-layer membranes is explored.•Increasing polyelectrolyte concentration increases multilayer thickness.•Polyelectrolyte concentration has a regime-dependent effect on pore size.•Pore structure may be tailored by controlling polyelectrolyte-salt interactions.
Direction selectivity (DS) is an important neuronal property in the visual system, but how DS is generated beyond the retina remains controversial. Here, we report a close correspondence between the ...preferred direction (PD) and the morphology of DS cells in the optic tectum. Ca2+ imaging in cells expressing the genetically encoded Ca2+ indicator GCaMP3 and multiphoton-targeted patch-clamp recordings allowed us to compare structure and function in single neurons. The arbors of differently tuned cell types showed stereotypic differences in shape and laminar profile within the tectal neuropil. Excitatory synaptic inputs were directionally tuned and matched the PD of spike output in these cells, while inhibitory inputs were selective for nonpreferred directions. Functional Ca2+ imaging in afferent axons showed a matching laminar distribution of DS presynaptic activity. Hence, different directions are represented in different layers, which suggests a simple mechanism for how tectal neurons acquire directional tuning in a nascent circuit.
► Ca2+ imaging reveals directional tuning in zebrafish tectum in specific cell types ► Neurons with different preferred directions arborize in distinct tectal layers ► Excitatory input to direction-selective neurons is directionally tuned ► Pre- and postsynaptic directional Ca2+ signals colocalize in different layers.
How stimulus motion is processed in visual centers beyond the retina is unclear. Using two-photon-targeted recordings, Gabriel et al. show that morphologically distinct cell classes exist in the zebrafish tectum that specialize in processing different stimulus directions.
Caesarian section is one of the most commonly performed surgeries in India. Determination of the incidence as well as the clinical and financial burden of post caesarian surgical site infection ...(SSI), is of critical importance for all the stakeholders for rational and fair allocation of resources.
This study was a prospective observational case-control study. The mean direct and indirect cost of treatment for the cases were compared with the control patients. An unpaired t-test was used to compare the mean between the two groups.
Out of 2024 patients, who underwent caesarian section during the study period, 114 had acquired incisional surgical site infection (ISSI), with the infection incidence being 5.63%. The total cost of illness due to post caesarian ISSI was almost three times higher compared to the non-infected matched control group. (P<0.0001). An average length of hospital stay in the ISSI patient group was 10 days longer than that in the control group (P<0.0001) and importantly total length of antimicrobial therapy(LOT) in patients with ISSI was also almost three times higher than the control group (P<0.0001).
The development of post caesarian SSI imposes a significant clinical as well as a financial burden. The study highlights the necessity of taking effective preventive measures to decrease the incidence of SSI.
The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for ...use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider’s recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.
Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this ...under-recognized lesion.
A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1-2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging.
In the prospective series, the mean age was 50 years (range, 41-55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%-2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web.
A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.
A principal task of the visual system is to detect and classify moving objects in the visual environment. Information about the size of an object is critical for selecting appropriate behavioral ...responses. Object size is encoded in retinal ganglion cell (RGC) activity. Little is known, however, about how inputs from the multitude of RGC subtypes are distributed to higher visual centers and how information is combined from these feature-selective inputs.
Here we show that in the zebrafish optic tectum, prey- or predator-like moving targets evoke activity in distinct groups of RGC fibers dependent on target size, demonstrating a retinal origin of tectal size classification. Small-size-selective retinal inputs are relatively more frequent in the most superficial layer of the tectal neuropil, whereas large-size-selective inputs predominate in deeper layers. Monostratified superficial interneurons (SINs) process large-size- and small-size-selective signals dependent on their dendritic target layer, consistent with the retinal input organization. Further downstream, small- and large-sized objects are encoded in population activity of separate sets of tectal neurons.
Ethologically relevant size classes are preferentially processed in different layers of the tectal neuropil. The tectum categorizes visual targets on the basis of retinally computed size information, suggesting a critical role in visually guided response selection.
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•Visual targets of distinct behavioral value are classified in the retinotectal pathway•Size classification begins in distinct sets of RGC afferents in tectum•Tectal neurons receive size-selective synaptic input dependent on target layer•Separate sets of downstream tectal neurons encode object size
Classifying the size of visual objects is critical for rapid behavioral decision making. Preuss, Trivedi et al. show that in the zebrafish retinotectal pathway, object size is classified in distinct retinal inputs and is encoded in separate sets of tectal neurons, suggesting a key role of tectal microcircuits in response selection.
In the present study, a series of 3-((6-(2,6-dichloroquinolin-3-yl)-4-aryl-1,6-dihydro-pyrimidin-2-yl)thio)propanenitriles 5a–o were synthesized and subjected to molecular properties prediction and ...drug-likeness model score by Molinspiration property calculation toolkit and MolSoft software, respectively. Compound 5m (4-OCH3) was found to be maximum drug-likeness model score (0.42). Among the screened compounds, 5m showed the most promising antitubercular activity with MIC of 0.20μg/mL, while compounds 5g, 5k and 5m displayed broad spectrum antibacterial activity against all the bacterial strains. Moreover, compound 5k was found to be the most potent antifungal agent. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 5g, 5k and 5m was escorted by low cytotoxicity.
Summary
Background Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal haemorrhage (UGIH) but the magnitude and characteristics of this reaction and ...possible interaction with concurrent Non‐Steroidal Anti‐Inflammatory Drug (NSAID) therapy are unknown.
Aim To evaluate systematically the risk of UGIH with SSRIs, including interaction with NSAIDs.
Methods We searched PubMED, Science Citation Index, and trial registries for data on SSRIs, NSAIDs and UGIH. We evaluated spontaneous case reports from pharmacovigilance databases.
Results Random effects meta‐analysis of four observational studies involving 153 000 patients showed an odds ratio of 2.36 (95% CI: 1.44–3.85; P = 0.0006) for SSRI associated UGIH. The odds ratio increased to 6.33 (95% CI: 3.40–11.8; P < 0.00001) with concomitant NSAIDs. In patients aged above 50 years with no UGIH risk factors, the Number‐Needed‐to‐Harm per year is 411 for SSRIs alone, and 106 with concomitant NSAIDs. Analysis of 101 spontaneous reports showed that UGIH occurred after a median of 25 weeks with SSRIs. Around 67% of these patients were on NSAIDs.
Conclusions Selective serotonin reuptake inhibitor use, alone and in combination with NSAIDs, substantially increases the risk of UGIH. Clinicians should consider this when managing patients at risk of, or presenting with UGIH.
Abstract
In motor control, the brain not only sends motor commands to the periphery, but also generates concurrent internal signals known as corollary discharge (CD) that influence sensory ...information processing around the time of movement. CD signals are important for identifying sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from neurons in the zebrafish optic tectum, we discovered an inhibitory synaptic signal, temporally locked to spontaneous and visually driven locomotion. This motor-related inhibition was appropriately timed to counteract visually driven excitatory input arising from the fish’s own motion, and transiently suppressed tectal spiking activity. High-resolution calcium imaging revealed localized motor-related signals in the tectal neuropil and the upstream torus longitudinalis, suggesting that CD enters the tectum via this pathway. Together, our results show how visual processing is suppressed during self-motion by motor-related phasic inhibition. This may help explain perceptual saccadic suppression observed in many species.
The metabolic repertoire in nature is augmented by generating hybrid metabolites from a limited set of gene products. In mycobacteria, several unique complex lipids are produced by the combined ...action of fatty acid synthases and polyketide synthases (PKSs), although it is not clear how the covalently sequestered biosynthetic intermediates are transferred from one enzymatic complex to another. Here we show that some of the 36 annotated fadD genes, located adjacent to the PKS genes in the Mycobacterium tuberculosis genome, constitute a new class of long-chain fatty acyl-AMP ligases (FAALs). These proteins activate long-chain fatty acids as acyl-adenylates, which are then transferred to the multifunctional PKSs for further chain extension. This mode of activation and transfer of fatty acids is contrary to the previously described universal mechanism involving the formation of acyl-coenzyme A thioesters. Similar mechanisms may operate in the biosynthesis of other lipid-containing metabolites and could have implications in engineering novel hybrid products.
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