Shigella flexneri is the causative agent of dysentery. For pathogens, iron is a critical micronutrient as its bioavailability is usually low in bacterial niches. This metal is involved in critical physiological processes mainly as a component of important metabolic molecules involved in redox reactions. Usually bacteria respond to fluctuations in iron availability to regulate iron acquisition and other iron-related functions. Recently the close metabolic feedback between iron and riboflavin, another pivotal biological redox agent, began to draw attention in bacteria. This is a widespread biological phenomenon, partly characterized by the coordination of regulatory responses to iron and riboflavin, probably owed to the involvement of these cofactors in common processes. Nonetheless, no systematic analyses to determine the extent of this regulatory effect have been performed in any species. Here, the transcriptomics responses to iron, riboflavin, iron in the presence of riboflavin and riboflavin in the presence of iron were assessed and compared in S. flexneri. The riboflavin regulon had a 43% overlap with the iron regulon. Notably, the presence of riboflavin highly increased the number of iron-responsive genes. Reciprocally, iron drastically changed the pool of riboflavin-responsive genes. Gene ontology (GO) functional terms enrichment analysis showed that biological processes were distinctively enriched for each subgroup of responsive genes. Among the biological processes regulated by iron and riboflavin were iron uptake, amino acids metabolism and electron transfer for ATP synthesis. Thus, iron and riboflavin highly affect the transcriptomics responses induced by each other in S. flexneri. GO terms analysis suggests that iron and riboflavin coordinately regulate specific physiological functions involving redox metabolism.Individuals higher in trait worry exhibit increased activation in Broca's area during inhibitory processing tasks. To identify whether such activity represents an adaptive mechanism supporting top-down control, functional and effective connectivity of Broca's area were investigated during a task of inhibitory control. fMRI data obtained from 106 participants performing an emotion-word Stroop task were examined using psychophysiological interaction and Granger Causality (GC) analyses. Findings revealed greater directed connectivity from Broca's to amygdala in the presence of emotional distraction. Furthermore, a predictive relationship was observed between worry and the asymmetry in effective connectivity, with worriers exhibiting greater directed connectivity from Broca's to amygdala. When performing the task, worriers with greater GC directional asymmetry were more accurate than worriers with less asymmetry. Present findings indicate that individuals with elevated trait worry employ a mechanism of top-down control in which communication from Broca's to amygdala fosters successful compensation for interference effects.
To observe and characterize cone degeneration and regeneration in a selective metronidazole-mediated ablation model of ultraviolet-sensitive (UV) cones in zebrafish using in vivo optical coherence tomography (OCT) imaging.

Twenty-six
zebrafish were imaged with OCT, treated with metronidazole to selectively kill UV cones, and imaged at 1, 3, 7, 14, 28, or 56 days after ablation. Regions 200 × 200 µm were cropped from volume OCT scans to count individual UV cones before and after ablation. Fish eyes were fixed, and immunofluorescence staining was used to corroborate cone density measured from OCT and to track monocyte response.

Histology shows significant loss of UV cones after metronidazole treatment with a slight increase in observable blue cone density one day after treatment (Kruskal, Wallis,
= 0.0061) and no significant change in blue cones at all other timepoints. Regenerated UV cones measured from OCT show significantly lower density than pre-cone-ablation at 14, 28, and 56 days after ablation (analysis of variance,
< 0.01,
< 0.0001,
< 0.0001, respectively, 15.9% of expected nonablated levels). Histology shows significant changes to monocyte morphology (mixed-effects analysis,
< 0.0001) and retinal position (mixed-effects analysis,
< 0.0001).

OCT can be used to observe loss of individual cones selectively ablated by metronidazole prodrug activation and to quantify UV cone loss and regeneration in zebrafish. OCT images also show transient changes to the blue cone mosaic and inner retinal layers that occur concomitantly with selective UV cone ablation.

Profiling cone degeneration and regeneration using in vivo imaging enables experiments that may lead to a better understanding of cone regeneration in vertebrates.
Profiling cone degeneration and regeneration using in vivo imaging enables experiments that may lead to a better understanding of cone regeneration in vertebrates.
To determine whether increased growth differentiation factor 15 (GDF15) in aqueous humor (AH) is associated with worse visual field loss in patients with pseudoexfoliative glaucoma (PXG).

We recruited 12 patients (6 males, 6 females) with primary open-angle glaucoma (POAG) or PXG who were scheduled to undergo glaucoma surgery. AH was obtained from the initial peripheral paracentesis for the planned glaucoma surgery, and GDF15 levels were quantified with enzyme-linked immunosorbent assay by an investigator masked to clinical information. Humphrey visual field testing was performed as a part of routine care; results were obtained by reviewing the medical record.

AH GDF15 was detectable in patients with POAG and PXG. Increased AH GDF15 was significantly associated with worse mean deviation in patients with POAG (
= -0.94; 95% confidence interval [CI], -0.99 to -0.33;
= 0.02) and PXG (
= -0.92; 95% CI, -0.99 to -0.41;
= 0.01).

AH GDF15 is detectable in patients with PXG and POAG. Elevated AH GDF15 is strongly associated with worse mean deviation in both subgroups. These findings suggest that GDF15 may be a molecular marker of glaucoma severity that is generalizable to multiple types of glaucoma regardless of the underlying etiology.

This study provides proof of concept that GDF15, a molecular marker of retinal ganglion stress that was initially identified in rodent models, may have clinical utility as a measure of glaucoma severity not only in POAG but also in PXG.
This study provides proof of concept that GDF15, a molecular marker of retinal ganglion stress that was initially identified in rodent models, may have clinical utility as a measure of glaucoma severity not only in POAG but also in PXG.The rapid spread of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has become a public health emergency of international concern. The outbreak was characterized as a pandemic by the World Health Organization (WHO) in March 2020. The most characteristic symptom of patients with COVID-19 is respiratory distress. Some patients may also show neurologic signs and symptoms ranging from headache, nausea, vomiting, and confusion to anosmia, ageusia, encephalitis, and stroke. Coronaviruses are known pathogens with neuroinvasive potential. There is increasing evidence that coronavirus infections are not always confined to the respiratory tract. CNS involvement can occur in susceptible individuals and may contribute overall morbidity and mortality in the acute setting. In addition, postinfectious, immune-mediated complications in the convalescent period are possible. Awareness and recognition of neurologic manifestations is essential to guide therapeutic decision-making because the current outbreak continues to unfold.Mild cognitive impairment (MCI) is characterized by evidence of cognitive impairment with minimal disruption of instrumental activities of daily living and carries a substantial risk of progression of dementia. Whereas current guidelines support a relatively minimalistic workup to identify reversible or structural causes, the field has witnessed the rapid development of various sophisticated imaging, biomarker, and genetic investigations in the past few years. The role of these investigations in routine practice is uncertain. Similarly, although there are no approved treatments for MCI, neurologists may experience uncertainty about using cholinesterase inhibitors or other medications or supplements that have been studied in MCI with limited success, particularly when patients or families are keen to try pharmacologic options. Given these uncertainties, and the paucity of high-quality data in the literature, we sought expert opinion from around the globe on how to investigate and treat patients with MCI. Similar questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.We present a novel epilepsy fellow-driven transfer clinic model and discuss the challenges experienced in finding sustainability; this is timely as many pioneering transition clinics are dissolving across North America. The goal of this clinic was to improve patient care and satisfaction, as measured by a post-visit telephone survey. Unfortunately, our transfer clinic model proved unsustainable due to several factors, broadly categorized as (1) cultural-societal differences between the pediatric and adult health care environments, (2) staffing issues, (3) lack of an established standardized process for transfer of care, and (4) financial and administrative barriers. We suggest potential solutions to these challenges, but the fate of transition and transfer of care clinics may ultimately depend on implementation of practice, policy, and/or financial guidelines.
To systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.

We searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.

Sixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.

If optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. https://www.selleckchem.com/products/ginsenoside-rg1.html However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.
If optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.