High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients.

PURPOSE: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH. METHODS: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by "National Newborn Screening Program" (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET). RESULTS: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34-38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750. CONCLUSION: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

A strong quick-release biointerface in mussels mediated by serotonergic cilia-based adhesion.

The mussel byssus stem provides a strong and compact mechanically mismatched biointerface between living tissue and a nonliving biopolymer. Yet, in a poorly understood process, mussels can simply jettison their entire byssus, rebuilding a new one in just hours. We characterized the structure and composition of the byssus biointerface using histology, confocal Raman mapping, phase contrast-enhanced microcomputed tomography, and advanced electron microscopy, revealing a sophisticated junction consisting of abiotic biopolymer sheets interdigitated between living extracellular matrix. The sheet surfaces are in intimate adhesive contact with billions of motile epithelial cilia that control biointerface strength and stem release through their collective movement, which is regulated neurochemically. We posit that this may involve a complex sensory pathway by which sessile mussels respond to environmental stresses to release and relocate.

Comparison of Bipolar vascular sealing and conventional back-table dissection in terms of post-renal transplant drainage and back-table preparation times.

OBJECTIVE: The usage of vessel sealing devices has been gaining popularity in all surgical specialties. Post-renal transplant drain placement is a common practice among transplant surgeons. However, prolonged drainage accompanied by surgical wound complications and perirenal fluid collections is a frequent complication experienced by the recipients. This study aimed to compare Bipolar vascular sealing with conventional back-table dissection in terms of post-renal transplant drainage duration, amount, surgical wound complication, and back-table preparation time. PATIENTS AND METHODS: A double-blind clinical study randomizes recipients into 2 groups, using Bipolar vascular sealing (Group 1) and conventional ligation (Group 2) back-table dissection. Variables such as recipient age, gender, body mass index (BMI), cause of end-stage renal disease, amount and duration of surgical drainage, back-table time, and cold ischemia time (CIT) were collected prospectively. RESULTS: Ninety-eight consecutive living donor (M/F: 69/29) renal transplant recipients were enrolled in this prospective randomized clinical trial. There were 49 patients in each group. The mean BMI was 26.76±4.57. There was no difference among the groups regarding recipient age, BMI, total drainage, and surgical drainage duration. The surgical site infection rate was not different between the two groups. Group 1 had significantly shorter back-table time, with mean back-table time being 15.26±2.51 minutes in Group 1 and 28.83±6.27 minutes in Group 2 (p<0.001). The CIT was also significantly different between the 2 groups (p<0.001). In Group 1, the recorded CIT was 43.3±11.4, and in Group 2, 57.1±13.3 minutes. CONCLUSIONS: The use of Bipolar vascular sealing to seal lymphatic vessels at the back-table is feasible, safe, and easy to perform. It also expedites the dissection and shortens the time required for back-table graft preparation.

A single-center kidney transplantation experience in children with low weight: is low weight a contraindication?

OBJECTIVE: Kidney transplantation (KT) might be difficult for underweight kids (under 15 kg). Our goal was to convey information on KT in underweight children. PATIENTS AND METHODS: The study's target population consisted of children (age 18) weighing 15 kg or fewer who received KT at our facility between January 2018 and June 2021. A retrospective analysis was performed on demographic and clinical data, including age, gender, primary disease, pretransplant dialysis status, recipient weight, recipient body mass index (BMI), surgical approach type (intraperitoneal/extraperitoneal), complications, graft status (functioning/failed), patient survival, and immunological data. RESULTS: There were 94 pediatric KTs completed. Thirty-three patients were included when the selection criteria were applied. The mean recipient weight was 11.45 [6.7-15] kg, and the average patient age was 3.36 [1-7]. Three (9.9%) patients had kidney transplants from dead adult donors, whereas thirty (90.1%) patients underwent live donor kidney transplantation (LDKT). While the intraperitoneal (IPA) technique was used in 19 cases, the extraperitoneal (KT) strategy was used on 14 patients (EPA). The donor BMI was 28.24 [19.6-42] kg/m2, and the mean donor weight was 78.13 [55-109] kg. Bridectomy was necessary because five individuals experienced ileus. IPA was performed in each of these patients during LDKT. Following IPA, a 2-year-old patient with a BMI of 16 kg/m2 had renal allograft compartment syndrome and required graft nephrectomy. CONCLUSIONS: Pediatric patients weighing 15 kg or fewer can get kidney transplants successfully. Gastrointestinal problems are relatively uncommon with EPA, even though there is no agreement on the best surgical strategy.

From binary AB to ternary ABC supraparticles.

Control over the assembly and morphology of nanoscale functional building blocks is of great importance to hybrid and porous nanomaterials. In this paper, by combining different types of spherical nanoparticles with different size ratios in a hierarchical assembly process which allows us to control the final structure of multi-component assemblies, we discuss self-assembly of an extensive range of supraparticles, labelled as AB particles, and an extension to novel ternary particles, labelled as ABC particles. For supraparticles, the organization of small nanoparticles is known to be inherently related to the size ratio of building blocks. Therefore, we studied the formation of supraparticles prepared by colloidal self-assembly using small silica nanoparticles (SiO2 NPs) attached on the surface of large polystyrene latex nanoparticles (PSL NPs) with a wide size ratio range for complete and partial coverage, by controlling the electrostatic interactions between the organic and inorganic nanoparticles and their concentrations. In this way hierarchically ordered, stable supraparticles, either fully covered or partially covered, were realized. The partially covered, stable AB supraparticles offer the option to create ABC supraparticles of which the fully covered shell contains two different types of nanoparticles. This has been experimentally confirmed using iron oxide (Fe3O4) nanoparticles together with silica nanoparticles as shell particles on polystyrene core particles. Cryo-electron tomography was used to visualize the AB binary and ABC ternary supraparticles and to determine the three-dimensional structural characteristics of supraparticles formed under different conditions.

Cells Dynamically Adapt to Surface Geometry by Remodeling Their Focal Adhesions and Actin Cytoskeleton.

Cells probe their environment and adapt their shape accordingly via the organization of focal adhesions and the actin cytoskeleton. In an earlier publication, we described the relationship between cell shape and physiology, for example, shape-induced differentiation, metabolism, and proliferation in mesenchymal stem cells and tenocytes. In this study, we investigated how these cells organize their adhesive machinery over time when exposed to microfabricated surfaces of different topographies and adhesive island geometries. We further examined the reciprocal interaction between stress fiber and focal adhesion formation by pharmacological perturbations. Our results confirm the current literature that spatial organization of adhesive sites determines the ability to form focal adhesions and stress fibers. Therefore, cells on roughened surfaces have smaller focal adhesion and fewer stress fibers. Our results further highlight the importance of integrin-mediated adhesion in the adaptive properties of cells and provide clear links to the development of bioactive materials.

Impact of social contacts on SARS-CoV-2 exposure among healthcare workers.

BACKGROUND: Healthcare workers (HCWs) have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. Strict measures generally focus on the patient-to-HCW contacts. However, interactions between the HCWs also pose a high risk for SARS-CoV-2 exposure. AIMS: This study was aimed to investigate the effect of social contacts on the level of SARS-CoV-2 exposure risk among workers by broadening the current risk assessment algorithm. METHODS: Contact tracing records of the workers in a large university hospital between 19th March and 31st December 2020 were analysed. Multivariate conditional logistic regression models were estimated to evaluate factors associated with high-risk exposure for contacts among workers. RESULTS: Of the 329 exposed clusters, 260 (79%) were HCW-to-HCW contacted clusters. High-risk exposure was higher in the HCW-to-HCW contacts (44%), when compared to the patient-to-HCW contacts (5%) (P < 0.001). A total of 1827 HCWs contacted a laboratory-confirmed COVID-19-positive co-worker. Among the HCW-to-HCW contacts, high-risk exposure was higher in the support staff (49%, P < 0.001), in non-patient care settings (47%, P < 0.001) and in the social contacts (57%, P < 0.001). Social contacts between workers increased the high-risk exposure (adjusted odds ratio: 3.50, 95% confidence interval 2.62-4.69) in multivariate analysis. CONCLUSIONS: A significant association between social contacts among workers and high-risk exposure of SARS-CoV-2 was observed. The results of the study emphasize the need for policies regarding the improved protection of HCWs in social settings in addition to patient care services.

TWO OPPOSITE PHENOTYPES OF GLUCOSE DISORDERS IN A FAMILY WITH HETEROZYGOUS P.SER453LEU (C.1358C> T) MUTATION IN THE GLUCOKINASE (GCK) GENE: MATURITY ONSET DIABETES IN YOUNG AND INSULINOMA.

Background: Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while loss-of-function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods: The proband, an 11-year-old male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulin-dependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7µU/mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Post-pancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results: Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion: We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.

Multiscale characterization of pathological bone tissue.

Bone is a complex natural material with a complex hierarchical multiscale organization, crucial to perform its functions. Ultrastructural analysis of bone is crucial for our understanding of cell to cell communication, the healthy or pathological composition of bone tissue, and its three-dimensional (3D) organization. A variety of techniques has been used to analyze bone tissue. This article describes a combined approach of optical, scanning electron, and transmission electron microscopy for the ultrastructural analysis of bone from the nanoscale to the macroscale, as illustrated by two pathological bone tissues. By following a top-down approach to investigate the multiscale organization of pathological bones, quantitative estimates were made in terms of calcium content, nearest neighbor distances of osteocytes, canaliculi diameter, ordering, and D-spacing of the collagen fibrils, and the orientation of intrafibrillar minerals which enable us to observe the fine structural details. We identify and discuss a series of two-dimensional (2D) and 3D imaging techniques that can be used to characterize bone tissue. By doing so we demonstrate that, while 2D imaging techniques provide comparable information from pathological bone tissues, significantly different structural details are observed upon analyzing the pathological bone tissues in 3D. Finally, particular attention is paid to sample preparation for and quantitative processing of data from electron microscopic analysis.

Building Reversible Nanoraspberries.

The adsorption mechanism of small positively charged silica nanoparticles (SiO2 NPs) onto larger polystyrene latex nanoparticles (PSL NPs) forming hybrid particles was studied. CryoTEM showed the morphology of these supraparticles to be raspberry-like. After surface modification of the SiO2 NPs, the optimum pH regime to initiate the formation of nanoraspberries was determined. Thereafter, their size evolution was evaluated by dynamic light scattering for different surface charge densities. Reversibility of nanoraspberry formation was shown by cycling the pH of the mixture to make interparticle forces either attractive or repulsive, while their stability was confirmed experimentally. The number of SiO2 NPs on the PSL NPs as determined with cryoTEM matched the theoretically expected maximum number. Understanding and controlling the relevant parameters, such as size and charge of the individual particles and the Debye length, will pave the way to better control of the formation of nanoraspberries and higher-order assemblies thereof.

Self-agglomerated collagen patterns govern cell behaviour.

Reciprocity between cells and their surrounding extracellular matrix is one of the main drivers for cellular function and, in turn, matrix maintenance and remodelling. Unravelling how cells respond to their environment is key in understanding mechanisms of health and disease. In all these examples, matrix anisotropy is an important element, since it can alter the cell shape and fate. In this work, the objective is to develop and exploit easy-to-produce platforms that can be used to study the cellular response to natural proteins assembled into diverse topographical cues. We demonstrate a robust and simple approach to form collagen substrates with different topographies by evaporating droplets of a collagen solution. Upon evaporation of the collagen solution, a stain of collagen is left behind, composed of three regions with a distinct pattern: an isotropic region, a concentric ring pattern, and a radially oriented region. The formation and size of these regions can be controlled by the evaporation rate of the droplet and initial collagen concentration. The patterns form topographical cues inducing a pattern-specific cell (tenocyte) morphology, density, and proliferation. Rapid and cost-effective production of different self-agglomerated collagen topographies and their interfaces enables further study of the cell shape-phenotype relationship in vitro. Substrate topography and in analogy tissue architecture remains a cue that can and will be used to steer and understand cell function in vitro, which in turn can be applied in vivo, e.g. in optimizing tissue engineering applications.

Spontaneous organization of supracolloids into three-dimensional structured materials.

Periodic nano- or microscale structures are used to control light, energy and mass transportation. Colloidal organization is the most versatile method used to control nano- and microscale order, and employs either the enthalpy-driven self-assembly of particles at a low concentration or the entropy-driven packing of particles at a high concentration. Nonetheless, it cannot yet provide the spontaneous three-dimensional organization of multicomponent particles at a high concentration. Here we combined these two concepts into a single strategy to achieve hierarchical multicomponent materials. We tuned the electrostatic attraction between polymer and silica nanoparticles to create dynamic supracolloids whose components, on drying, reorganize by entropy into three-dimensional structured materials. Cryogenic electron tomography reveals the kinetic pathways, whereas Monte Carlo simulations combined with a kinetic model provide design rules to form the supracolloids and control the kinetic pathways. This approach may be useful to fabricate hierarchical hybrid materials for distinct technological applications.

Prediction of vehicle occupants injury at signalized intersections using real-time traffic and signal data.

Intersections are among the most dangerous roadway facilities due to the existence of complex movements of traffic. Most of the previous intersection safety studies are conducted based on static and highly aggregated data such as average daily traffic and crash frequency. The aggregated data may result in unreliable findings because they are based on averages and might not necessarily represent the actual conditions at the time of the crash. This study uses real-time event-based detection records, and crash data to develop predictive models for the vehicle occupants' injury severity. The three-year (2017-2019) data were acquired from the arterial highways in the City of Tallahassee, Florida. Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) classifiers were used to identify the important factors on the vehicle occupants' injury severity prediction. The performance comparison of the two classifiers revealed that the XGBoost has a higher balanced accuracy score than RF. Using the XGBoost classifier, five topmost influential factors on injury prediction were identified. The factors are the manner of the collision, through and right-turn traffic volume, arrival on red for through and right-turn traffic, split failure for through traffic, and delays for through and right-turn traffic. Moreover, the partial dependency plots of the influential variables are presented to reveal their impact on vehicle occupant injury prediction. The knowledge gained from this study will be useful in developing effective proactive countermeasures to mitigate intersection-related crash injuries in real-time.

Tendon-Derived Biomimetic Surface Topographies Induce Phenotypic Maintenance of Tenocytes In Vitro.

The tenocyte niche contains biochemical and biophysical signals that are needed for tendon homeostasis. The tenocyte phenotype is correlated with cell shape in vivo and in vitro, and shape-modifying cues are needed for tenocyte phenotypical maintenance. Indeed, cell shape changes from elongated to spread when cultured on a flat surface, and rat tenocytes lose the expression of phenotypical markers throughout five passages. We hypothesized that tendon gene expression can be preserved by culturing cells in the native tendon shape. To this end, we reproduced the tendon topographical landscape into tissue culture polystyrene, using imprinting technology. We confirmed that the imprints forced the cells into a more elongated shape, which correlated with the level of Scleraxis expression. When we cultured the tenocytes for 7 days on flat surfaces and tendon imprints, we observed a decline in tenogenic marker expression on flat but not on imprints. This research demonstrates that native tendon topography is an important factor contributing to the tenocyte phenotype. Tendon imprints therefore provide a powerful platform to explore the effect of instructive cues originating from native tendon topography on guiding cell shape, phenotype, and function of tendon-related cells.

Modifying the thickness, pore size, and composition of diatom frustule in Pinnularia sp. with Al3+ ions.

Diatoms are unicellular photosynthetic algae that produce a silica exoskeleton (frustule) which exposes a highly ordered nano to micro scale morphology. In recent years there has been a growing interest in modifying diatom frustules for technological applications. This is achieved by adding non-essential metals to the growth medium of diatoms which in turn modifies morphology, composition, and resulting properties of the frustule. Here, we investigate the frustule formation in diatom Pinnularia sp., including changes to overall morphology, silica thickness, and composition, in the presence of Al3+ ions at different concentrations. Our results show that in the presence of Al3+ the total silica uptake from the growth medium increases, although a decrease in the growth rate is observed. This leads to a higher inorganic content per diatom resulting in a decreased pore diameter and a thicker frustule as evidenced by electron microscopy. Furthermore, 27Al solid-state NMR, FIB-SEM, and EDS results confirm that Al3+ becomes incorporated into the frustule during the silicification process, thus, improving hydrolysis resistance. This approach may be extended to a broad range of elements and diatom species towards the scalable production of silica materials with tunable hierarchical morphology and chemical composition.

Intermolecular channels direct crystal orientation in mineralized collagen.

The mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril.

Anatomic variations associated with antrochoanal polyps.

OBJECTIVE: Although more than a century has passed since antrochoanal polyps (ACPs) were first defined, etiopathogenesis still remains unclear. The aim of this study was to investigate the relationship between ACPs and sinonasal cavity variations. SUBJECTS AND METHODS: One hundred and forty-four patients with ACP on paranasal sinus computed tomography scans (ACP group) and 160 paranasal sinuses without ACP (control group) were included into the study. The study group was evaluated in respect of the presence of retention cyst in the contralateral maxillary sinus and sinus bone wall sclerosis thickening. Both groups were also compared with respect to the frequency of sinonasal anatomic variations, nasal septal deviation, variations of the uncinate process insertion, concha bullosa, paradoxical middle turbinate, and accessory maxillary sinus ostium. In the ACP group, the cases with septal deviation (SD) were also evaluated whether the deviation convexity was towards the polyp side or the opposite side. In addition, the posterior extension of ACPs were evaluated in three groups as middle meatus, nasopharynx, and oropharynx extension. RESULTS: The prevalence of retention cyst, sinus wall sclerosis thickening, SD, and accessory maxillary ostium was significantly higher in the ACP group. A negative directional correlation was determined between the SD side and ACP side. When the ACP extensions were examined, middle meatus extension was seen in 32.6%, nasopharynx in 56.3%, and oropharynx in 11.1%. CONCLUSION: Accessory ostium may be an accelerating factor in the transformation of retention cyst to ACP. Furthermore, the changes in the nasal passage airflow on the opposite side suggest that SD contributes to this process.

Genotype-phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey.

BACKGROUND: Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients. OBJECTIVE: To present genotype-phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2. MATERIALS AND METHODS: Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated. RESULTS: A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty. CONCLUSION: There is no significant genotype-phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.