Whole-exome sequencing analysis reveals co-segregation of a COL20A1 missense mutation in a Pakistani family with striate palmoplantar keratoderma

Abstract

Palmoplantar keratoderma (PPK) is a rare group of excessive skin disorder characterized by thickness over the palms and soles. The striate palmoplantar keratoderma (PPKS) is a form in which hyperkeratotic lesions are restricted to the pressure regions extending longitudinally in the length of each finger to the palm. Dominantly inherited mutations in genes including desmoglein 1, desmoplakin and keratin 1 have been suggested as genetic causes of PPKS. In this study, we investigated a three-generation Pakistani family segregating PPKS phenotype in autosomal dominant fashion to identify genetic cause in this family. We have performed whole-exome and Sanger sequencing followed by in silico bioinformatics analysis to pinpoint candidate mutation associated with PPK. Revealed a novel heterozygous mutation (NM_020882.2, COL20A1 c. 392C > G; p.Ser131Cys) in the loop region close to fibronectin type III-1 domain of the c ollagen 20 α1. This variant was not found in our in-house 219 ethnically matched Pakistani unaffected controls and showed minor allele frequency of 3.4 × 10⁻⁵ in Exome Aggregation Consortium database containing exome data of 59,464 worldwide individuals. It was assigned as "pathogenic" by in silico prediction tools. Previously, association of mutation in the COL14A1, one of the paralogous gene of COL20A1, with PPK was reported in the study with a Chinese family. Our study proposes COL20A1 gene as another potential candidate gene for PPKS which expand the spectrum of collagen proteins in the pathogenicity of PPK.

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Change-of-Direction Biomechanics: Is What’s Best for Anterior Cruciate Ligament Injury Prevention Also Best for Performance?

Abstract

Change-of-direction maneuvers (e.g., side-step cutting) are an important aspect of performance in multi-directional sports, but these maneuvers are also associated with anterior cruciate ligament (ACL) injury. Despite this, the impact of biomechanics on ACL injury risk and performance is often examined in isolation. The purpose of this review was to examine the alignment between biomechanical recommendations for ACL injury prevention and performance with regard to change-of-direction maneuvers. Several studies linking change-of-direction biomechanics to both ACL injury risk and performance were examined. A degree of overlap was identified between biomechanical strategies that could both reduce ACL injury risk and enhance performance during change-of-direction maneuvers. A fore-foot footfall pattern along with trunk rotation and lateral flexion in the intended cutting direction were identified as biomechanical strategies that could both reduce potentially hazardous knee joint moments and enhance change-of-direction speed. Minimizing knee valgus during change-of-direction maneuvers may also reduce ACL injury risk, with this biomechanical strategy found to have no impact on performance. Certain biomechanical strategies proposed to reduce ACL injury risk were linked to reduced change-of-direction performance. A narrow foot placement and "soft" landings with greater knee flexion were identified as ACL injury prevention strategies that could have a negative impact on performance. The findings of this review emphasize the need to consider both ACL injury risk and performance when examining the biomechanics of change-of-direction maneuvers.

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Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency Intubation: A Randomized Clinical Trial.

Related Articles

Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency Intubation: A Randomized Clinical Trial.

JAMA. 2018 May 01;319(17):1790-1801

Authors: Durrmeyer X, Breinig S, Claris O, Tourneux P, Alexandre C, Saliba E, Beuchée A, Jung C, Levy C, Marchand-Martin L, Marcoux MO, Dechartres A, Danan C, PRETTINEO Research Group

Abstract
Importance: Propofol or a combination of a synthetic opioid and muscle relaxant are both recommended for premedication before neonatal intubation but have yet to be compared.
Objective: To compare prolonged desaturation during neonatal nasotracheal intubation after premedication with atropine-propofol vs atropine-atracurium-sufentanil treatment.
Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial (2012-2016) in 6 NICUs in France that included 173 neonates requiring nonemergency intubation. The study was interrupted due to expired study kits and lack of funding.
Interventions: Eighty-nine participants were randomly assigned to the atropine-propofol group and 82 to the atropine-atracurium-sufentanil group before nasotracheal intubation.
Main Outcomes and Measures: The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis using mixed models. Secondary outcomes assessed the characteristics of the procedure and its tolerance.
Results: Of 173 neonates randomized (mean gestational age, 30.6 weeks; mean birth weight, 1502 g; 71 girls), 171 (99%) completed the trial. Of 89 infants, 53 (59.6%) in the atropine-propofol group vs 54 of 82 (65.9%) in the atropine-atracurium-sufentanil group achieved the primary outcome (adjusted RD, -6.4; 95% CI, -21.0 to 8.1; P = .38). The atropine-propofol group had a longer mean procedure duration than did the atropine-atracurium-sufentanil group (adjusted RD, 1.7 minutes; 95% CI, 0.1-3.3 minutes; P = .04); a less frequent excellent quality of sedation rate, 51.7% (45 of 87) vs 92.6% (75 of 81; P < .001); a shorter median time to respiratory recovery, 14 minutes (IQR, 8-34 minutes) vs 33 minutes (IQR, 15-56 minutes; P = .002), and shorter median time to limb movement recovery, 18 minutes (IQR, 10-43 minutes) vs 36 minutes (IQR, 19-65 minutes; P = .003). In the 60 minutes after inclusion, Spo2 was preserved significantly better in the atropine-propofol group (time × treatment interaction P  = .02). Of the atropine-propofol group 20.6% had head ultrasound scans that showed worsening intracranial hemorrhaging (any or increased intraventricular hemorrhage) in the 7 days after randomization vs 17.6% in the atropine-atracurium-sufentanil group (adjusted RD, 1.2; 95% CI, -13.1 to 15.5, P = .87). Severe adverse events occurred in 11% of the atropine-propofol group and in 20% of the atropine-atracurium-sufentanil group.
Conclusions and Relevance: Among neonates undergoing nonemergency nasotracheal intubation, the frequency of prolonged desaturation did not differ significantly between atropine used with propofol or atropine used with atracurium and sufentanil. However, the study may have been underpowered to detect a clinically important difference, and further research may be warranted.
Trial Registration: ClinicalTrials.gov Identifier: NCT01490580, EudraCT number: 2009-014885-25.

PMID: 29715354 [PubMed - in process]

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Estimation of critical end-test torque using neuromuscular electrical stimulation of the quadriceps in humans

Abstract

Characterization of critical power/torque (CP/CT) during voluntary exercise requires maximal effort, making difficult for those with neuromuscular impairments. To address this issue we sought to determine if electrically stimulated intermittent isometric exercise resulted in a critical end-test torque (ETT) that behaved similar to voluntary CT. In the first experiment participants (n = 9) completed four bouts of stimulated exercise at a 3:2 duty cycle, at frequencies of 100, 50, 25 Hz, and a low frequency below ETT (Sub-ETT; ≤ 15 Hz). The second experiment (n = 20) consisted of four bouts at a 2:2 duty cycle—two bouts at 100 Hz, one at an intermediate frequency (15–30 Hz), and one at Sub-ETT. The third experiment (n = 12) consisted of two bouts at 50 Hz at a 3:2 duty* cycle with proximal blood flow occlusion during one of the bouts. ETT torque was similar (p ≥ 0.43) within and among stimulation frequencies in experiment 1. No fatigue was observed during the Sub-ETT bouts (p > 0.05). For experiment 2, ETT was similar at 100 Hz and at the intermediate frequency (p ≥ 0.29). Again, Sub-ETT stimulation did not result in fatigue (p > 0.05). Altering oxygen delivery by altering the duty cycle (3:2 vs. 2:2; p = 0.02) and by occlusion (p < 0.001) resulted in lower ETT values. Stimulated exercise resulted in an ETT that was consistent from day-to-day and similar regardless of initial torque, as long as that torque exceeded ETT, and was sensitive to oxygen delivery. As such we propose it represents a parameter similar to voluntary CT.

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Impact of tumor localization on the outcomes of surgery for an intrahepatic cholangiocarcinoma

Abstract

Background

Intrahepatic cholangiocarcinoma (ICC) shows differing clinical outcomes depending on its localization.

Methods

We reviewed the surgical outcomes of 104 ICC patients who underwent liver resection at our institution. We divided ICC into hilar type (HICC) and peripheral type (PICC) depending on positive contact with the hepatic hilum on preoperative computed tomography (CT).

Results

The survival outcomes were significantly poorer in HICC patients. HICCs showed a larger tumor size and more frequent bile duct invasion, lymph node metastasis, and non-curative resection than PICC. Resections for HICC had greater blood loss and required a longer operation time, larger hepatectomy, and more frequent extrahepatic bile duct resection. HICCs, even if small in size, also showed a greater tendency to metastasize to the lymph nodes of the hepatoduodenal ligament. Univariate analysis of the ICCs in our current cohort revealed that tumor size, multiple tumors, bile duct invasion, lymph node metastasis, non-curative resection, and HICC are associated with a poorer overall survival outcome. Multivariate analysis indicated that multiple tumors and non-curative resection were independent prognostic factors for survival. Among the curative resection cases, however, survival did not differ significantly between HICC and PICC. The accuracy rate of our CT-based classification for the pathological classification was 81.7%.

Conclusions

HICC shows more frequent bile duct invasion and lymph node metastasis, requires more extensive surgery, and has a higher rate of non-curative resection than PICC. However, if curative resection is achieved, the survival outcomes are expected to be equivalent between HICC and PICC.

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Correction to: Identification of novel mutations in FFPE lung adenocarcinomas using DEPArray sorting technology and next-generation sequencing

In the original article, part of Table 1 headings and entries were missing. The correct Table is as shown below. The original article has been corrected.

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Differences in the oral health status and oral hygiene practices according to the extent of post‐stroke sequelae

Journal of Oral Rehabilitation, EarlyView.


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