Illusory figures demonstrate the visual system’s ability to infer surfaces under conditions of fragmented sensory input. To investigate the role of midlevel visual area V4 in visual surface ...completion, we used multielectrode arrays to measure spiking responses to two types of visual stimuli: Kanizsa patterns that induce the perception of an illusory surface and physically similar control stimuli that do not. Neurons in V4 exhibited stronger and sometimes rhythmic spiking responses for the illusion-promoting configurations compared with controls. Moreover, this elevated response depended on the precise alignment of the neuron’s peak visual field sensitivity (receptive field focus) with the illusory surface itself. Neurons whose receptive field focus was over adjacent inducing elements, less than 1.5° away, did not show response enhancement to the illusion. Neither receptive field sizes nor fixational eye movements could account for this effect, which was present in both single-unit signals and multiunit activity. These results suggest that the active perceptual completion of surfaces and shapes, which is a fundamental problem in natural visual experience, draws upon the selective enhancement of activity within a distinct subpopulation of neurons in cortical area V4.
Infectious diseases are common causes of morbidity and mortality worldwide. Susceptibility to infection is highly heritable; however, little has been done to identify the genetic determinants ...underlying common infectious diseases. One GWAS was performed using 23andMe information about self-reported infections; we set out to confirm previous loci and identify new ones using medically diagnosed infections.
We used the electronic health record (EHR)-based biobank at Vanderbilt and diagnosis codes to identify cases of 12 infectious diseases in white patients: urinary tract infection, pneumonia, chronic sinus infections, otitis media, candidiasis, streptococcal pharyngitis, herpes zoster, herpes labialis, hepatitis B, infectious mononucleosis, tuberculosis (TB) or a positive TB test, and hepatitis C. We selected controls from patients with no diagnosis code for the candidate disease and matched by year of birth, sex, and calendar year at first and last EHR visits. We conducted GWAS using SAIGE and transcriptome-wide analysis (TWAS) using S-PrediXcan. We also conducted phenome-wide association study to understand associations between identified genetic variants and clinical phenotypes.
We replicated three 23andMe loci (p ≤ 0.05): herpes zoster and rs7047299-A (p = 2.6 × 10
) and rs2808290-C (p = 9.6 × 10
;); otitis media and rs114947103-C (p = 0.04). We also identified 2 novel regions (p ≤ 5 × 10
): rs113235453-G for otitis media (p = 3.04 × 10
), and rs10422015-T for candidiasis (p = 3.11 × 10
). In TWAS, four gene-disease associations were significant: SLC30A9 for otitis media (p = 8.06 × 10
); LRP3 and WDR88 for candidiasis (p = 3.91 × 10
and p = 1.95 × 10
); and AAMDC for hepatitis B (p = 1.51 × 10
).
We conducted GWAS and TWAS for 12 infectious diseases and identified novel genetic contributors to the susceptibility of infectious diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor ...standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.
Time to diagnosis (TTD) concerns teenagers and young adults (TYA) with cancer and may affect outcome.
Healthcare records from 105 TYA in a regional cancer service were assessed to document events ...from 1st symptom to treatment start. Detailed pathway construction was possible for 104 patients and allowed a multidisciplinary panel review of each pathway with assessment of good practice and lessons for the future.
1st presentation was to primary care in 86, and 93% consulted in primary care before diagnosis. Routes to Diagnosis were 45% via urgent 2 Week Wait pathways and 38% as emergency referrals. Total Interval (time from 1st presentation to treatment start) was median 63 (range 1-559) days, varying within/between diagnoses. Patient interval (time from 1st symptom to 1st presentation) was longest for lymphoma, carcinoma and bone tumour (medians: 9, 12, 20 days). Overall, time in primary care was short (median 3, range 0-537 days) compared to secondary care (median 29, range 0-195 days) and longest for lymphoma, carcinoma, brain/CNS (medians: 10, 15, 16 days). Specialist Care interval (time from 1st specialist visit to treatment start) was longest for bone, brain/CNS, lymphoma, carcinoma (medians: 30, 33, 36, 48 days). 40% pathways were rated as showing good/best practice but 16% were less than satisfactory. Continued safety-netting/support was identified from primary care but analysis suggested opportunities for improvement in transition through secondary care.
Previous reports of prolonged TTD have focused on delay in referral from primary care but this study suggests that this might be reduced by optimising management in secondary care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Theta (3–9 Hz) and gamma (30–100 Hz) oscillations have been observed at different levels along the hierarchy of cortical areas and across a wide set of cognitive tasks. In the visual system, the ...emergence of both rhythms in primary visual cortex (V1) and mid-level cortical areas V4 has been linked with variations in perceptual reaction times.1–5 Based on analytical methods to infer causality in neural activation patterns, it was concluded that gamma and theta oscillations might both reflect feedforward sensory processing from V1 to V4.6–10 Here, we report on experiments in macaque monkeys in which we experimentally assessed the presence of both oscillations in the neural activity recorded from multi-electrode arrays in V1 and V4 before and after a permanent V1 lesion. With intact cortex, theta and gamma oscillations could be reliably elicited in V1 and V4 when monkeys viewed a visual contour illusion and showed phase-to-amplitude coupling. Laminar analysis in V1 revealed that both theta and gamma oscillations occurred primarily in the supragranular layers, the cortical output compartment of V1. However, there was a clear dissociation between the two rhythms in V4 that became apparent when the major feedforward input to V4 was removed by lesioning V1: although V1 lesioning eliminated V4 theta, it had little effect on V4 gamma power except for delaying its emergence by >100 ms. These findings suggest that theta is more tightly associated with feedforward processing than gamma and pose limits on the proposed role of gamma as a feedforward mechanism.
•Visual stimulation elicits theta and gamma oscillations in V1 and V4•Theta and gamma oscillations interact in time•Although lesion of V1 eliminates V4 theta oscillations, gamma oscillations survive•Gamma oscillations still contain stimulus information but emerge delayed without V1
Kienitz et al. show that, upon visual stimulation, V1 and V4 show theta and gamma oscillations, which interacted in terms of phase-to-amplitude coupling. Lesion of V1, the major input source to V4, eliminated V4 theta oscillations. In contrast, V4 gamma oscillations were less affected and still contained stimulus information but emerged delayed (>100 ms).
Whatʼs New in Shock, September 2020? Cox, Michael C; Efron, Philip A; Brakenridge, Scott C
Shock (Augusta, Ga.),
2020-September, Letnik:
54, Številka:
3
Journal Article
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid ...(HGA) in AKU but the dose-response relationship has not been previously studied.
Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone.
A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy.
In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range.
EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463.
Mesoblastic nephroma is the most frequent renal tumor in newborns and young infants, and the cellular type is characterized by an ETV6–NTRK fusion, which constitutively activates the ...tropomyosin‐related kinase (TRK) signaling pathway. Larotrectinib is a highly selective TRK inhibitor with activity in adult and pediatric patients who have TRK fusions. We present a rare case of a patient with mesoblastic nephroma metastatic to bone who had a dramatic response to larotrectinib.
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