Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.

B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

OBJECTIVES: During human pregnancy placental extravillous trophoblasts replace the vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling these arteries into distensible low resistance vessels to promote placental perfusion. The present study, determined whether B-flow/ spatio-temporal image correlation (STIC) M-mode ultrasonography provides an in vivo imaging method to digitally quantify spiral artery luminal distensibility, as a physiological index of spiral artery remodeling, during advancing stages of normal human pregnancy. METHODS: A prospective longitudinal observational study was conducted to quantify spiral artery distensibility, i.e. vessel luminal diameter at systole minus diameter at diastole, by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1), growth factors that modulate events important in spiral artery remodeling, were quantified in a subset of the subjects at the first, second and third semesters. RESULTS: Median [first quartile, third quartile] spiral artery distensibility progressively increased (P < 0.0001) between the first trimester (0.17 [0.14, 0.21]), second (0.23 [0.18, 0.28]) and third (0.26 [0.21, 0.35]) trimesters of pregnancy. Spiral artery volume flow (ml/cardiac cycle) progressively increased (P < 0.001) between the first 2.49 [1.38, 4.99], second 3.86 [2.06, 6.91] and third 7.79 [3.83, 14.98] trimesters. Coinciding with the elevation in spiral artery distensibility, the median ratio of serum PlGF/sFlt-1 levels increased (P < 0.001) between the first (7.2 [4.5, 10], second (22.7 [18.6, 42.2]) and third (56.2 [41.9, 92.5] trimesters. CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in vivo imaging technology to digitally quantify structural/physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. This article is protected by copyright. All rights reserved.

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of xenon and gallium sources on the detection and mapping of lithium in Li-containing materials by using ToF-SIMS combined FIB-SEM.

Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy-based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF-SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF-SIMS with a recently launched Xe ion source FIB-SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF-SIMS attached to the FIB-SEM with Ga and Xe ion sources were discussed for Al incorporated Li7 La3 Zr2 O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Low ion contaminated zone, high sputtering yield and low straggling obtained from Monte Carlo simulations are the main advantages of Xe ion sources. The Li detection efficiency for Xe is higher than Ga source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2 Zr2 O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase. LAY DESCRIPTION: Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy-based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF-SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF-SIMS with a recently launched Xe ion source FIB-SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF-SIMS attached to the FIB-SEM with Ga and Xe ion sources were discussed for Al incorporated Li7 La3 Zr2 O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Results were also supported from Monte Carlo simulations of ion-atom interactions. The Li detection resolution of xenon is much higher than gallium source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2 Zr2 O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

Are there possible associations between MnSOD and GPx1 gene variants for laryngeal cancer risk or disease progression?

Laryngeal squamous cell carcinoma (LSCC) is a multifaceted and genomically complex disease and cellular and preclinical studies have demystified wide ranging molecular mechanisms which underpin its development and progression and resistance against wide ranging molecular therapeutics. Oxidative stress is a widely studied molecular mechanism and reportedly involved in carcinogenesis. Increasingly it is being realized that accumulation of Reactive Oxygen Species (ROS) activates defensive mechanism to counteract oxidative stress induced damage. Manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) are important members of defensive machinery. We investigated whether the polymorphisms of MnSOD (Ala-9Val, rs4880) and GPx1 (Pro198Leu, rs1050450) are associated with LSCC and also evaluated possible interactions between these polymorphisms and various lifestyle factors or pathological features of patients. For this purpose, 67 LSCC patients and 73 healty controls were enrolled. Molecular assessment of MnSOD and GPx1 variants were determined with polymerase chain reaction-restriction fragment length polymorphism techniques. We found that the frequency of both heterozygous PL genotype and P allele was considerably higher in patients with advanced tumor stage (T3/T4) than in those with early tumor stage (T1/T2) (OR= 5.106; 95% CI=1.372-19.004; p<0.001, OR=5.787; 95% CI =1.564-21.414; p<0.001 respectively). Although the frequency of ValVal/LL combine genotype was significantly decreased (OR=0.204, 95% CI=0.055-0.760; p=0.021), the frequency of ValAla/PL combine genotypes was higher in patients with stage T3/T4 than in those patients with stage T1/T2 (p=0.027). Consequently, we have concluded that variants of GPx1 and MnSOD should not be considered as a risk factor of LSCC, only may be accepted as a prognostic markers. Use of new technologies such as metabolomics and deep DNA sequencing will prove to be helpful in developing a deeper knowledge related to how cancer cell metabolism adapts and provides a buffer against increased oxidative stress.

Extended characterization of Corynebacterium pyruviciproducens based on clinical strains from Canada and Switzerland.

The species Corynebacterium pyruviciproducens was described in 2010 based on the features of a single strain. In this report, we describe the chemotaxonomic and phenotypic characteristics of 11 C. pyruviciproducens clinical strains isolated in Switzerland and Canada in comparison to the strain 06-17730(T). Heterogeneities within the type strain were found in the 16S rRNA gene and in biochemical markers. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification of this species could not be achieved since currently this bacterial species is not included in the corresponding database. Reliable identification is obtained only with sequence-based identification tools. Results of antimicrobial susceptibility testing of this species with an extended panel of antimicrobials are presented here for the first time.

First-trimester fetal cardiac examination using spatiotemporal image correlation, tomographic ultrasound and color Doppler imaging for the diagnosis of complex congenital heart disease in high-risk patients.

OBJECTIVE: A four-dimensional (4D) fetal echocardiographic technique utilizing spatiotemporal image correlation, tomographic ultrasound imaging display (STIC-TUI echo) and color Doppler has previously been shown to be effective in displaying the examination planes constituting the extended cardiac examination. The aim of this study was to evaluate the performance of this first-trimester STIC-TUI echo technique in identifying complex congenital heart disease (CHD) in high-risk pregnancies. METHODS: This was a prospective study of patients presenting at first-trimester screening who were at high risk for CHD owing to pregestational diabetes, in-vitro fertilization (IVF), increased nuchal translucency (NT) thickness, first-trimester tricuspid regurgitation or reversed ductus venosus (DV) a-wave, a previous child with CHD or who were on anticonvulsant medication. First-trimester STIC-TUI echo was performed, and the findings were correlated with second-trimester echocardiography and post-delivery echo findings in survivors. RESULTS: One hundred and sixty-four fetuses from 152 patients were enrolled (77 diabetics, 38 IVF, 14 with increased NT, 23 cases of tricuspid regurgitation or reversed a-wave in the DV, 22 with prior CHD and two on anticonvulsants). STIC-TUI echo was abnormal in 20 (12%), showing atrioventricular canal defect (n = 9), hypoplastic left heart (n = 2), pulmonary stenosis (n = 2), right aortic arch (n = 1), interrupted aortic arch (n = 1), tricuspid atresia (n = 1), heterotaxy (n = 1), persistent truncus arteriosus (n = 1), double outlet right ventricle and ventricular septal defect (n = 1) and double inlet ventricle with transposition of the great arteries (n = 1). 85% of these anomalies were evident in the four-chamber view plane of the TUI display, and the remainder were diagnosed in the outflow tract planes with color Doppler imaging. In 13, CHD was isolated while seven had extracardiac anomalies. Thirteen fetuses had aneuploidy and all 13 underwent first-trimester termination of pregnancy. In the remaining seven, second-trimester echocardiography and neonatal echo/postmortem examination confirmed anomalies (two stillborn neonates, one neonatal death, four live births). Two cases of CHD missed by first-trimester STIC-TUI echo were diagnosed on second-trimester echo. Accordingly, first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. CONCLUSIONS: First-trimester 4D echocardiography using a standardized application of STIC, TUI and color Doppler imaging is effective in displaying the imaging planes that are necessary for achieving the diagnosis of complex cardiac anomalies in high-risk patients. Optimal imaging of the four-chamber view with two-dimensional ultrasound is the major determinant of successful volume acquisition.

Semiquantitative classification of ductus venosus blood flow patterns.

OBJECTIVES: To identify the range of waveform abnormalities in the ductus venosus (DV) characterized by their timing in the cardiac cycle and to evaluate if they can be categorized into distinct patterns. METHODS: DV velocity ratios were calculated from peak velocities during ventricular systole (S), end-systolic ventricular relaxation (v), early diastole (D) and atrial systole (a) (S/v, S/D, v/D, S/a, v/a and D/a ratios). The ratios were converted to their Z-scores and elevation > 2 SD was assigned as abnormal. Combinations of ratio abnormalities were grouped to define distinct waveform patterns and their distribution was related to the clinical presentation. RESULTS: Five-hundred and forty-two abnormal DV waveforms fell into three principal patterns. In Pattern 1 only the a-wave-related ratios were abnormal (180, 33.2%), in Pattern 2 the v/D ratio was abnormal (143, 26.3%) and in Pattern 3 combinations of a-wave abnormalities in the presence of a normal v/D ratio were normal (94, 17.3%). CONCLUSIONS: Interpretation of venous waveform patterns is complex because the multiphasic waveforms reflect events in the cardiac cycle that may be differentially affected by clinical pathology. We sought to present a classification for the DV flow profile that characterizes abnormal flow confined to atrial systole and occurs during ventricular relaxation or during holodiastole. Further research is warranted to determine the significance of these patterns in specific fetal conditions.

Correlation analysis of ductus venosus velocity indices and fetal cardiac function.

OBJECTIVE: To examine the relationships between the ductus venosus (DV) pulsatility index for veins (PIV), individual DV velocity ratios and diastolic and global myocardial cardiac function. METHODS: Doppler measurements of the DV, atrioventricular (AV) valves and ventricular in- and outflow were analyzed. The DV-PIV and velocity ratios for individual phases (systole (S), end-systolic relaxation (v), early diastole (D), atrial systole (a), and S/v, S/D, S/a, v/D, v/a and D/a ratios) were calculated. The ratio of early and late diastolic peak velocities across AV valves was calculated (E/A ratio). Left modified myocardial performance index (MPI) was calculated from time intervals between valve clicks defining isovolumetric contraction/relaxation and ejection times. All values were transformed to Z-scores. The distributions of DV velocity ratios and DV-PIV were correlated with cardiac Doppler parameters. RESULTS: A total of 1163 examinations from 213 fetuses, most of which were at risk for cardiac dysfunction, were included in the study. In 742 the PIV was normal and in 421 PIV was elevated > 2 SD above the normal mean. The DV-PIV correlated with velocity ratios (P < 0.0001) but not with E/A ratios and the MPI. S/v and v/D ratios were related to tricuspid and mitral E/A ratios and left ventricular MPI. The S/D ratio was only related to both E/A ratios. There was no relationship between a-wave-related velocity ratios and cardiac function. CONCLUSIONS: Velocity ratios of the DV show relationships with cardiac function that are not reflected by the PIV alone. In cases of suspected fetal cardiac dysfunction based on elevated DV-PIV, analysis of velocity ratios or direct cardiac evaluation is suggested to determine the underlying pathophysiology.

Effects of pleural opening on respiratory function tests in cardiac surgery: a prospective study.

PURPOSE: To show the effects on lung function of the opening pleura in patients undergoing cardiac surgery. SUBJECTS AND METHODS: 66 patients were included. Patients were allocated into two groups. In group 1 (n=21) pleura was intact, in group 2 (n=45) pleura was opened. Both groups were compared prospectively in terms of preoperative and on the post-operative 5th day pulmonary function tests (PFT), preoperative, postoperative first and fifth day arterial blood gas analysis, preoperative and postoperative first day mixt venous oxygen saturation, bleeding, operation periods, pulmonary complications, intensive care and hospital stay period and mortality. RESULTS: There was significant decrease in all PFT indicators on 5th post-operative day in group 2 (p < 0.01). Although there was a significant decrease in FEV1 on 5th post-operative day in group 1 (p < 0.001), other pulmonary functions parameters were not change significantly (p > 0.025). In group 2 much more decline in pulmonary function test parameters than group 1 were observed (p < 0.05). There was not statistically significant difference in blood gas analysis and mixed venous oxygen saturation values in group 1 (p > 0.05). But in group 2 except pH and PaCO2, other blood gas measurements were significantly decreased on the postoperative first and fifth day (p < 0.008). In group 2 except pH and PCO2, other parameters were less than the other Group (p < 0.01). The drained amount was still significantly higher in group 2 (p < 0.001). The frequency of the revision due to bleeding was observed much more in group 2. CONCLUSIONS: Protection of the integrity of pleura may have positive effects on pulmonary functions in cardiac surgery.

Factors that Influence Placement of Gastrostomy Tube in Infants with Complex Congenital Heart Disease: A Single Center Study.

BACKGROUND: Factors that determine the need for Gastrostomy tube (G-tube) placement in infants with complex congenital heart defects (CHD) are variable. We aim to identify factors that improve counseling of expectant parents regarding postnatal outcomes and management. METHODS: We performed a retrospective review of medical record of infants with prenatal diagnoses of complex CHD between 2015-2019 in a single tertiary care center and assessed risk factors for G-tube placement with linear regression. RESULTS: Of the 105 eligible infants with complex CHD, 44 infants required G-tube (42%). No significant association was observed between G-tube placement and chromosomal abnormalities, cardiopulmonary bypass time or type of CHD. Median days on noninvasive ventilation (4 [IQR 2-12] vs. 3 [IQR 1-8], p = 0.035), time at which gavage-tube feeds were started postoperatively (3 [IQR 2-8] vs. 2 [IQR 0-4], p = 0.0013), time to reach full-volume gavage-tube feeds (6 [IQR 3-14] vs. 5 [IQR 0-8], p = 0.038) and intensive care unit (ICU) length of stay (LOS) (41 [IQR: 21 - 90] vs. 18 [IQR: 7 - 23], p < 0.01) were associated with G-tube placement. Infants with ICU LOS duration longer than median had almost 7 times the odds of requiring a G-tube (OR: 7.23, 95% CI: 2.71-19.32; by regression). CONCLUSIONS: Delay in initiation and in reaching full-volume gavage-tube feeds after cardiac surgery, increased number of days spent on non-invasive ventilation and in the ICU were found to be significant predictors for G-tube placement. The type of CHD and the need for cardiac surgery were not significant predictors for G-tube placement.

Factors associated with ureteral strictures following ureteroscopy for impacted ureteral stones? A multicenter study by EAU-YAU endourology and urolithiasis working party.

OBJECTIVE: To determine the relation between ureteral stone impaction and ureteral stricture formation and associated factors. MATERIAL AND METHODS: We retrospectively analyzed the medical records of all patients who underwent endoscopic ureteral stone surgery for impacted ureteral stone at three academic institutions in Turkey, United Kingdom and Spain between June 2019 and January 2022. Examined parameters included patient demographics, stone side, size and localization, time between initiation of symptoms and surgery, type of ureteroscopy (rigid/flexible), presence of nephrostomy or double-J stent prior to URS, intraoperative complications (avulsion/perforation, stone-free status, number of procedures required for stone-free status, postoperative imaging results. RESULTS: A total of 41 patients whom 25 were male and 16 were female, from 3 institutions were included the study. The mean age of the patients was 48.2 ±â€¯13.5 years. The median largest diameter of the stones was 9 mm (IQR: 8 mm). Total 14 (34.1%) patients developed ureteral strictures following ureteroscopy. There was no difference between patients who developed ureteral strictures and patients who did not developed strictures in terms of stone laterality, stone location, hydronephrosis and multiplicity, p = 0.58, p = 0.14, p = 0.79 and p = 0.31. Patients who developed ureteral strictures had a higher rate of preoperative urinary diversion such as nephrostomy or DJS, p = 0.000. CONCLUSION: Interruption of urine passage through ureter via urinary diversion such as nephrostomy or DJS stent prior to ureteral stone surgery might lead ureteral stricture formation in the postoperative period.

COVID-19: booster(s) vs. hospitalization and Intensive Care Unit admission.

OBJECTIVE: As the pandemic continues, different vaccine protocols have been implemented to maintain the protection of vaccines and to provide protection against new variants. The aim of this study was to assess hospitalized patients' vaccination status and document the efficacy of boosters. PATIENTS AND METHODS: The patients that were hospitalized due to COVID-19 were enrolled from 28 hospitals in Turkey for five months from September 2021. 5,331 confirmed COVID-19 patients from collaborating centers were randomly enrolled to understand/estimate the distribution of vaccination status in hospitalized patients and to compare the efficacy of vaccination/booster protocols. RESULTS: 2,779 men and 2,552 women of which 2,408 (45.2%) were admitted to Intensive Care Units participated in this study. It was found that the highest risk reduction for all age groups was found in groups that received 4 doses. Four doses of vaccination for every 3.7 people under 50 years of age, for every 5.7 people in the 50-64 age group, and for every 4.3 people over 65 years of age will prevent 1 patient from being admitted to intensive care. Regardless of the type of vaccine, it was found that the risk of ICU hospitalization decreased in those who were vaccinated compared to those who were not vaccinated. Regardless of the type of vaccine, the ICU risk was found to decrease 1.25-fold in those who received 1 or 2 doses of vaccine, 1.18-fold in those who received 3 doses, and 3.26-fold in those who received 4 doses. CONCLUSIONS: The results suggested that the addition of a fourth dose is more effective in preventing intensive unit care even in disadvantaged groups.

Self-assembled peptide nanofiber templated one-dimensional gold nanostructures exhibiting resistive switching.

An amyloid-like peptide molecule self-assembling into one-dimensional nanofiber structure in ethanol was designed and synthesized with functional groups that can bind to gold ions. The peptide nanofibers were used as templates for nucleation and growth of one-dimensional gold nanostructures in the presence of ascorbic acid as reducing agent. We performed multistep seed-mediated synthesis of gold nanoparticles by changing peptide/gold precursor and peptide/reducing agent ratios. Gold nanostructures with a wide range of morphologies such as smooth nanowires, noodle-like one-dimensional nanostructures, and uniform aggregates of spherical nanoparticles were synthesized by use of an environmentally friendly synthesis method. Nanoscale electrical properties of gold-peptide nanofibers were investigated using atomic force microscopy. Bias dependent current (IV) measurements on thin films of gold-peptide nanofiber hybrid revealed tunneling dominated transport and resistive switching. Gold-peptide nanofiber composite nanostructures can provide insight into electrical conduction in biomolecular/inorganic composites, highlighting their potential applications in electronics and optics.

Amyloid inspired self-assembled peptide nanofibers.

Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force-distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies.

When are amniotic fluid viral PCR studies indicated in prenatal diagnosis?

OBJECTIVE: To determine which prenatal ultrasound findings indicate the need to also obtain PCR studies for viral genome in women undergoing midtrimester amniocentesis. METHODS: This was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral PCR testing for history or ultrasound based indication. Amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, Epstein-Barr virus, and parvovirus B19 using multiplex PCR study with multiple appropriate controls. Ultrasound findings were coded as normal or abnormal with 34 categories of ultrasound abnormality stratified into 18 subgroups. Relationships between these subgroups and karyotype/PCR results were tested by Pearson chi-square method or Fisher's exact test and overall logistic regression analysis. RESULTS: Amniotic fluid samples from 1191 patients were obtained for the study. Abnormal karyotype was detected in 5.4% of cases (64/1191), and PCR was positive in 6.5% of cases (77/1191). Abnormal fetal ultrasonographic findings were observed in 28.4% of cases (338/1191). There was an association between intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies or neural tube defects (NTDs), and PCR positivity. NTDs were associated with PCR positivity in fetuses with normal karyotype and nuchal thickening, cardiac or ventral wall defects were specifically associated with aneuploidy. CONCLUSION: Amniotic fluid viral PCR testing should be considered for fetuses with intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies, or NTDs. After aneuploidy is excluded, NTDs are associated with PCR positivity.

C.428_451 dup(24bp) mutation of the ARX gene detected in a Turkish family.

ARX mutations give rise to both syndromic and nonsyndromic forms of mental retardation (MR). We investigated the most common ARX mutations, c.428_451 dup(24bp) and c.333ins (GCG)7 in a series of 370 mentally retarded FMR1 (CGG)n expansion mutation negative Turkish patients using PCR amplification and high resolution MetaPhor agarose gel electrophoresis. Sequence analysis was also performed for confirmation and discrimination of the mutations. One patient representing non-syndromic X-linked MR showed an abnormal band pattern on agarose gel and sequence analysis of exon 2 of the ARX gene revealed that the patient had the c.428_451 dup(24bp) mutation. When we screened the family members, we found that his sister and mother were also carrier for the same mutation. The proband showed mild MR and subtle clinical findings like dysarthria and lack of fine motor functions. In conclusion, the patients with weak fine motor skills and positive family history for X-linked MR should be screened for the most common ARX gene mutations.