Congenital insensitivity to pain associated with PRDM12 mutation: Two case reports and a literature review

Background:PRDM12 is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known.Methods: The clinical data of two infants diagnosed with CIP associated with PRDM12 mutation were collected. A literature review was performed, and the clinical characteristics of 20 cases diagnosed with a mutation of PRDM12 were summarized and analyzed.Results: Two patients had pain insensitivity, tongue and lip defects, and corneal ulcers. The genomic analysis results showed that variants of PRDM12 were detected in the two families. The case 1 patient carried heterozygous variations of c.682+1G > A and c.502C > T (p.R168C), which were inherited from her father and mother, respectively. We enrolled 22 patients diagnosed with CIP through a literature review together with our cases. There were 16 male (72.7%) and 6 female (27.3%) patients. The age of onset ranged from 6 months to 57 years. The prevalence of clinic manifestation was 14 cases with insensitivity to pain (63.6%), 19 cases with self-mutilation behaviors (86.4%), 11 cases with tongue and lip defects (50%), 5 cases with mid-facial lesions (22.7%), 6 cases with distal phalanx injury (27.3%), 11 cases of recurrent infection (50%), 3 cases (13.6%) with anhidrosis, and 5 cases (22.7%) with global developmental delay. The prevalence of ocular symptoms was 11 cases (50%) with reduced tear secretion, 6 cases (27.3%) with decreased corneal sensitivity, 7 cases (31.8%) with disappeared corneal reflexes, 5.5 cases (25%, 0.5 indicated a single eye) with corneal opacity, 5 cases (22.7%) with corneal ulceration, and 1 case (4.5%) with a corneal scar.Conclusion: The syndrome caused by PRDM12 mutation is a clinically distinct and diagnosable disease that requires joint multidisciplinary management to control the development of the disease and minimize the occurrence of complications

Impact of selected non-steroidal anti-inflammatory pharmaceuticals on microbial community assembly and activity in sequencing batch reactors.

This study covers three widely detected non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX), as NSAIDs pollutants. The objective is to evaluate the impact of NSAIDs at their environmental concentrations on microbial community assembly and activity. The exposure experiments were conducted under three conditions (5 μg L-1 DCF, 5 μg L-1 DCF+5 μg L-1 IBP and 5 μg L-1 DCF+5 μg L-1 IBP+ 5 μg L-1 NPX) in sequencing batch reactors (SBRs) for 130 days. Removals of COD and NH4+-N were not affected but total nitrogen (TN) removal decreased. IBP and NPX had the high removal efficiencies (79.96% to 85.64%), whereas DCF was more persistent (57.24% to 64.12%). In addition, the decreased removals of TN remained the same under the three conditions (p > 0.05). The results of oxidizing enzyme activities, live cell percentages and extracellular polymeric substances (EPS) indicated that NSAIDs damaged the cell walls or microorganisms and the mixtures of the three NSAIDs increased the toxicity. The increased Shannon-Wiener diversity index suggested that bacterial diversity was increased with the addition of selected NSAIDs. Bacterial ribosomal RNA small subunit (16S) gene sequencing results indicated that Actinobacteria and Bacteroidetes were enriched, while Micropruina and Nakamurella decreased with the addition of NSAIDs. The enrichment of Actinobacteria and Bacteroidetes indicated that both of them might have the ability to degrade NSAIDs and thereby could adapt well with the presence of NSAIDs

Correction: Fate of artificial sweeteners through wastewater treatment plants and water treatment processes.

[This corrects the article DOI: 10.1371/journal.pone.0189867.]

Combined Behavioral and Mismatch Negativity Evidence for the Effects of Long-Lasting High-Definition tDCS in Disorders of Consciousness : A Pilot Study

Objective: To evaluate the effects of long-term High-definition transcranial direct current stimulation (HD-tDCS) over precuneus on the level of consciousness (LOC) and the relationship between Mismatch negativity (MMN) and the LOC over the therapy period in patients with Disorders of consciousness (DOCs). Methods: We employed a with-in group repeated measures design with an anode HD-tDCS protocol (2 mA, 20 min, the precuneus) on 11 (2 vegetative state and nine minimally conscious state) patients with DOCs. MMN and Coma Recovery Scale-Revised (CRS-R) scores were measured at four time points: before the treatment of HD-tDCS (T0), after a single session of HD-tDCS (T1), after the treatment of 7 days (T2) and 14 days (T3). A frequency-deviant oddball paradigm with two deviation magnitudes (standard stimulus: 1000 Hz, small deviant stimuli: 1050 Hz, large deviant stimuli: 1200 Hz) was adopted to elicit MMN. Results: Significant improvements of CRS-R score were found after 7-day (T2) and 14-day (T3) treatment compared with baseline (T0). Regarding the MMN, significant improvements of MMN amplitudes were observed after a single session of stimulation (T1), 7-day (T2) and 14-day treatment (T3) compared with baseline (T0). Additionally, there were significant negative correlations between CRS-R scores and MMN amplitudes elicited by both large and small deviant stimuli. Conclusion: Long-term HD-tDCS over precuneus might improve signs of consciousness in patients with DOCs as measured by CRS-R total scores, and MMN could be an assistant assessment in the course of tDCS treatment.peerReviewe

The relative abundances of bacteria in sludge samples of stable stage at phylum level.

<p>The abundance is presented in terms of percentage in total effective bacterial sequences in each sample. The color bar indicates the range of the percentage of a phylum. The sum of all phyla and unclassified phylum is 100%.</p

Pharmaceutical concentrations and mixture in SBRs.

<p>Pharmaceutical concentrations and mixture in SBRs.</p

Relative activities of oxidizing enzymes in activated sludge during the stable stage.

<p>The enzyme activity of the control is regarded as 100%. The relative activity is presented in the percentage of enzyme activity value in samples with enzyme activity value in the control. The relative activity is over 100% indicating an increase of enzyme activity (compared to the control). The relative activity is less 100% indicating a decrease of enzyme activity (compared to the control). asterisks (*) indicating the statistical difference from the control (<i>p</i> < 0.05).</p

Average removals of selected NSAIDs in the stable stage of each reactor.

<p>Average removals of selected NSAIDs in the stable stage of each reactor.</p

Average removal of COD, NH₄⁺–N and TN during stable stage of each reactor.

<p>Average removal of COD, NH₄⁺–N and TN during stable stage of each reactor.</p

Changes of EPS content in each sludge sample.

<p>EPS content is presented by the sum of PN and PS. PN and PS are normalized by volatile solid sludge (VSS). asterisks (*) indicates statistical difference from the control (<i>p</i> < 0.05).</p