Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

OBJECTIVE: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL). METHODS: AF samples, which had been obtained in the second trimester from asymptomatic women with short CL (< 15 mm) identified on transvaginal ultrasound, were analyzed. CL, funneling and the presence of AF 'sludge' were assessed in all cases close to the time of amniocentesis. A combination of liquid chromatography coupled with mass spectrometry and proton nuclear magnetic resonance spectroscopy-based metabolomics, as well as targeted proteomics analysis, including chemokines, cytokines and growth factors, was performed on the AF samples. To determine the robustness of the markers, we used six different machine-learning techniques, including deep learning, to predict preterm delivery < 34 weeks, latency period prior to delivery < 28 days after amniocentesis and requirement for admission to a neonatal intensive care unit (NICU). Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) with 95% CI, sensitivity and specificity. RESULTS: Of the 32 patients included in the study, complete omics, demographic and clinical data and outcome information were available for 26. Of these, 11 (42.3%) patients delivered ≥ 34 weeks, while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in CL between these two groups (mean ± SD, 11.2 ± 4.4 mm vs 8.9 ± 5.3 mm, P = 0.31). Using combined omics, demographic and clinical data, deep learning displayed good to excellent performance, with an AUC (95% CI) of 0.890 (0.810-0.970) for delivery < 34 weeks' gestation, 0.890 (0.790-0.990) for delivery < 28 days post-amniocentesis and 0.792 (0.689-0.894) for NICU admission. These values were higher overall than for the other five machine-learning methods, although each individual machine-learning technique yielded statistically significant prediction of the different perinatal outcomes. CONCLUSIONS: This is the first study to report use of AI with AF proteomics and metabolomics and ultrasound assessment in pregnancy. Machine learning, particularly deep learning, achieved good to excellent prediction of perinatal outcome in asymptomatic pregnant women with short CL in the second trimester. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Improved Multiscale Entropy Technique with Nearest-Neighbor Moving-Average Kernel for Nonlinear and Nonstationary Short-Time Biomedical Signal Analysis.

Analysis of biomedical signals can yield invaluable information for prognosis, diagnosis, therapy evaluation, risk assessment, and disease prevention which is often recorded as short time series data that challenges existing complexity classification algorithms such as Shannon entropy (SE) and other techniques. The purpose of this study was to improve previously developed multiscale entropy (MSE) technique by incorporating nearest-neighbor moving-average kernel, which can be used for analysis of nonlinear and non-stationary short time series physiological data. The approach was tested for robustness with respect to noise analysis using simulated sinusoidal and ECG waveforms. Feasibility of MSE to discriminate between normal sinus rhythm (NSR) and atrial fibrillation (AF) was tested on a single-lead ECG. In addition, the MSE algorithm was applied to identify pivot points of rotors that were induced in ex vivo isolated rabbit hearts. The improved MSE technique robustly estimated the complexity of the signal compared to that of SE with various noises, discriminated NSR and AF on single-lead ECG, and precisely identified the pivot points of ex vivo rotors by providing better contrast between the rotor core and the peripheral region. The improved MSE technique can provide efficient complexity analysis of variety of nonlinear and nonstationary short-time biomedical signals.

A reddish plaque in the forehead / Placa rojiza en la frente

No disponible

Novel approaches for quantitative electrogram analysis for intraprocedural guidance for catheter ablation: A case of a patient with persistent atrial fibrillation.

PURPOSE: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that causes stroke affecting more than 2.3 million people in the US and is increasing in prevalence due to ageing population causing a new global epidemic. Catheter ablation with pulmonary vein isolation (PVI) to terminate AF is successful for paroxysmal AF but suffers limitations with persistent AF patients as current mapping methods cannot identify AF active substrates outside of PVI region. Recent evidences in the mechanistic understating of AF pathophysiology suggest that ectopic activity, localized re-entrant circuit with fibrillatory propagation and multiple circuit re-entries may all be involved in human AF. The authors developed novel electrogram analysis methods and validated using optical mapping data from isolated rabbit hearts to accurately identify rotor pivot points. The purpose of this study was to assess the feasibility of generating patient-specific 3D maps for intraprocedural guidance for catheter ablation using intracardiac electrograms from a persistent AF patient using novel electrogram analysis methods. METHODS: A persistent AF patient with clinical appointment for AF ablation was recruited for this study with IRB approval. 1055 electrograms throughout the left and right atrium were obtained for offline analysis with the novel approaches such as multiscale entropy, multiscale frequency, recurrence period density entropy, kurtosis and empirical mode decomposition to generate patient specific 3D maps. 3D Shannon Entropy, Renyi Entropy and Dominant frequency maps were also generated for comparison purposes along with local activation time and complex fractionated electrogram analysis maps. RESULTS: Patient specific 3D maps were obtained for each of the different approach. The 3D maps indicate potential active sites outside the PVI region. However, presence of rotors cannot be confirmed and validation of these approaches is required on a larger dataset. CONCLUSIONS: Conventional catheter mapping system can be used for generating patient specific 3D maps with short time series analysis using the novel approaches.

Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Obstetrical correlates and perinatal consequences of neonatal hypoglycemia in term infants.

OBJECTIVE: To determine independent perinatal and intrapartum factors associated with neonatal hypoglycemia. METHOD: Of singleton pregnancies delivered at term in 2013; 318 (3.8%) neonates diagnosed with hypoglycemia were compared to 7955 (96.2%) neonate controls with regression analysis. RESULTS: Regression analysis showed that independent prenatal factors were multiparity (odds-ratio [OR] = 1.61), gestational age (OR = 0.68), gestational diabetes (OR = 0.22), macrosomia (OR = 4.87), small for gestational age neonate [SGA] (OR = 6.83) and admission cervical dilation (OR = 0.79). For intrapartum factors, only cesarean section (OR = 1.57) and last cervical dilation (OR = 0.92) were independently significantly associated with neonatal hypoglycemia. For biologically plausible risk factors, independent factors were cesarean section (OR = 4.18), gentamycin/clindamycin in labor (OR = 5.35), gestational age (OR = 0.59) and macrosomia (OR = 5.62). Mothers of babies with neonatal hypoglycemia had more blood loss and longer hospital stays, while neonates with hypoglycemia had worse umbilical cord gases, more neonatal hypoxic conditions, neonatal morbidities and NICU admissions. CONCLUSION: Diabetes was protective of neonatal hypoglycemia, which may be explained by optimum maternal glucose management; nevertheless macrosomia was independently predictive of neonatal hypoglycemia. Cesarean section and decreasing gestational age were the most consistent independent risk factors followed by treatment for chorioamnionitis and SGA. Further studies to evaluate these observations and develop preventive strategies are warranted.

Concomitant MAZE procedure during cardiac surgical procedures: is there any survival advantage in conversion to sinus rhythm?

AIM: The MAZE procedure, or concomitant intraoperative ablation, is an effective technique to restore long-term sinus rhythm (SR). The survival benefit of conversion to SR has been questioned recently. METHODS: We retrospectively evaluated the conversion rate to SR and its correlation with long-term survival in 209 patients with chronic AF, who had a MAZE procedure during cardiac surgical procedures between the years 2006 and 2011 at our institution. The mean age was 67.2 ± 12.0 years and 52.2% were female (N. = 109). Perioperative mortality was 5.74% (N. = 12). RESULTS: In univariate analysis, significant risk factors for perioperative mortality were age (P = 0.0033), duration of perfusion time (P = 0.0093), elevated creatinine (≥ 1.6 mg/dL, P = .02), and cross clamp time (P = 0.016). In multivariate analysis age (HR 2.97) and duration of perfusion time (HR 1.48) were the only independent predictors of perioperative mortality. The overall one and five-year survival rates were 88% ± 2.2%, and 76% ± 3.3%, respectively. The one and five-year survival rates for patients who converted and were in sinus rhythm (SR) upon discharge (N. = 154) were 88% ± 2.6% and 80% ± 3.5%, respectively. While the one and five-year survival rates for patients who were still in AF upon discharge (N. = 55) were 94% ± 3% and 82% ± 6.6%, respectively, this survival difference was not statistically significant (P = 0.24). Significant risk factors for long-term mortality included DM (P = 0.023), preoperative MI (P = 0.043), preoperative renal insufficiency (creatinine, ≥ 1.6 mg/dL, P = 0.02) and asthma/COPD (P = 0.040). In multivariate analysis, age (HR 1.048) and preoperative MI (HR 1.948) were the only independent predictors of long-term mortality. CONCLUSION: The surgical MAZE procedure has a high conversion rate, however, our data did not show improved survival in patients who converted to SR prior to discharge.

Direct interaction between NHERF1 and Frizzled regulates ß-catenin signaling.

Although Wnt-Frizzled (Fzd) signaling is critical in the pathophysiology of carcinomas, its role in human breast cancer has been difficult to establish. We show here that the adaptor protein Na(+)/H(+) exchange regulatory factor1 (NHERF1), a protein abundantly expressed in normal mammary epithelium, regulates Wnt signaling, maintaining low levels of ß-catenin activation. NHERF1's effects are mediated by direct interactions between one of its PSD-95/drosophila discs large/ZO-1 (PDZ) domains and the C-terminus of a subset of Fzd receptors. Loss of NHERF1 in breast cancer cell lines enhances canonical Wnt signaling and Wnt-dependent cell proliferation. Furthermore, the mammary glands of NHERF1-knockout mice exhibit increased mammary duct density accompanied by increased proliferation and ß-catenin activity. Finally, we demonstrate a negative correlation between NHERF1 expression and nuclear ß-catenin in human breast carcinomas. Taken together, these results provide a novel insight into the regulation of Wnt signaling in normal and neoplastic breast tissues, and identify NHERF1 as an important regulator of the pathogenesis of breast tumors.

USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23.

Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.

Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Haplogroup analysis supports a pathogenic role for the 7510T>C mutation of mitochondrial tRNA(Ser(UCN)) in sensorineural hearing loss.

We ascertained a large North American family, LMG309, with matrilineal transmission of non-syndromic, progressive sensorineural hearing loss (SNHL). There was no history of aminoglycoside exposure, and penetrance was complete. We sequenced the entire mitochondrial genome and identified the previously reported 7510T>C transition in the tRNA(Ser(UCN)) gene. The 7510T>C was homoplasmic in all affected members. The LMG309 mitochondrial sequence belongs to an unnamed subgroup of mitochondrial haplogroup H. We demonstrate that the previously reported Spanish family S258 carries 7510T>C on a different mitochondrial sub-haplogroup, H1. We did not detect 7510T>C among 79 Caucasian haplogroup H control samples, including 11 from sub-haplogroup H1 and one from the same sub-haplogroup as LMG309. Our results provide strong genetic evidence that 7510T>C is a pathogenic mutation that causes non-syndromic SNHL.

Self-retaining T-incision for difficult tracheotomy.

PROBLEM: To overcome difficulties in complicated tracheotomies through the use of a T-incision. STUDY DESIGN: Retrospective. METHODS: A T-shaped incision allows the wound edges to retract aside spontaneously, without the use of retractors. Four hundred and twelve patients were retrospectively evaluated; 203 received traditional tracheotomy incisions and 209 received a T-incision. RESULTS: Complication rates were similar for the two groups: 3 per cent in the traditional incision group and 4 per cent in the T-incision group (difference non-significant). CONCLUSIONS: The T-incision enables good control of bleeding and better exposure of the trachea. This incision was developed for use in difficult cases, such as patients with a short or thick neck, and complicated needle dilatation procedures. The T-incision is quick and suitable for a solo surgeon. Its cosmetic results are acceptable, and it has the same low complication rate as traditional incisions.

Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa.

In this work, we studied the proband in a small nuclear family of Chinese and Dutch/German descent and identified two novel mutations in the type VII collagen gene leading to recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens variant (HS-RDEB). The maternal mutation is a single base pair deletion of a cytosine nucleotide in exon 26, designated 3472delC, resulting in a frameshift and a premature termination codon (PTC) within the same exon, 7 bp downstream of the site of the mutation. The paternal mutation is a G-->A transition located at the 5' donor splice site within intron 51, designated IVS51 + 1G-->A. This mutation leads to the activation of a cryptic splice site, 32 bp downstream of the mutation site and to subsequent aberrant out-of-frame splicing, resulting in two alternative mRNA transcripts and a downstream PTC. To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family.

A novel missense mutation in the COL7A1 gene underlies epidermolysis bullosa pruriginosa.

Epidermolysis bullosa (EB) pruriginosa is a subtype of dominant dystrophic EB (DDEB), characterized by severe pruritus and blistering localized to the extensor surface of the extremities. EB pruriginosa exhibits extensive clinical heterogeneity with variable expression and delayed age of onset. Mutations in the COL7A1 gene, especially in glycine residues within Gly-X-Y repeats, have been shown to cause this form of DDEB. Here, we report a novel COL7A1 mutation in a Taiwanese pedigree with EB pruriginosa. Using PCR and direct sequence analysis we have identified a G-->T transversion at nucleotide 7097 in exon 92 of COL7A1, converting a glycine residue to valine (G2366V). The mutation resides within a consecutive, uninterrupted stretch of 17 Gly-X-Y residues in the triple-helical domain of type VII collagen. Interestingly, an affected member of this family also displayed elevated IgE levels, previously reported in some patients with this disorder. Our finding further implicates COL7A1 mutation in the pathogenesis of EB pruriginosa and underscores the heterogeneous clinical symptoms of glycine mutations in DDEB.

Hepatitis G virus in clotting factor concentrates.

Blood-borne hepatitis is a well-known complication in patients with bleeding disorders. A recently discovered parentally transmitted virus, hepatitis G [GB virus C (GBV-C)] has an increased prevalence in patients with haemophilia. Clotting factor concentrates derived from pools of human plasma currently undergo viral inactivation techniques known to be effective against hepatitis B, C and HIV; however, the effectiveness of current purification and viral inactivation techniques against newly discovered viruses such as GBV-C is unknown. A total of 37 vials of clotting factor concentrates manufactured in the USA from 1981 to 1995 were tested for the presence of GBV-C virus. All samples that did not undergo a specific viral inactivation step were positive for GBV-C. Viral inactivation techniques that did not uniformly remove GBV-C included vapour heat treatment and dry heat treatments for less than 144 h. All samples treated by pasteurization, solvent detergent or dry heat for 144 h, were negative for the presence of GBV-C.