The risk factors for silent aspiration: A retrospective case series and literature review.

AIM: Evidence shows that 20%-30% of patients who aspirate do so silently. Research to date has not demonstrated clear evidence to indicate which patients are at higher risk of silent aspiration. Our aim was to use univariate logistic regression analysis of retrospective case review to determine potential patterns of silent aspiration. MATERIALS AND METHODS: We conducted a retrospective analysis of 455 fiberoptic endoscopic evaluation of swallowing (FEES) reports. The patients were divided into four groups: G1 - neurological diseases (n = 93), G2 - head and neck surgery (n = 200), G3 - gastroenterological diseases (n = 94) and G4 - other patients (n = 68). Data included the occurrence or absence of saliva penetration or aspiration, of silent fluid/solid food penetration or aspiration, type of penetration or aspiration, occurrence of cranial nerve paresis, radiotherapy and tracheostomy. Univariate logistic regression was used to evaluate independent risk factors of silent aspiration in the study population. Three models with different independent variables were considered. RESULTS: There is a statistically significant difference in the frequency of occurrence of silent penetration and aspiration within the groups (p < 0.001), with intraglutative being most frequent. Fluid and food penetration and aspiration correlated with saliva penetration and aspiration in all groups (p < 0.001). Cranial nerve paresis (IX and X), radiotherapy and tracheostomy correlate with saliva penetration and aspiration (p = 0.020 for cranial nerve paresis; p = 0.004 for radiotherapy; p < 0.001 for tracheostomy). One hundred and fifteen patients (45.81%) in the subgroup of patients with intraglutative aspiration had cranial nerve paresis (IX, X or IX-X). CONCLUSIONS: Patients who should be prioritised or considered to be at a higher need of instrumental swallowing evaluation are those with IX and X cranial nerve paresis, tracheostomy and those who have had radiotherapy, with saliva swallowing problems, especially after paraganglioma, thyroid and parathyroid glands and middle and posterior fossa tumour surgery. WHAT THIS PAPER ADDS: What is already known on the subject Clinical signs of penetration or aspiration include coughing, throat clearing and voice changes, while silent penetration or aspiration patients aspirate without demonstrating any clinical symptoms. The most common consequences of silent aspiration include aspiration pneumonia, recurrent lower respiratory tract infections and respiratory failure. Additionally, malnutrition and dehydration can be indicators of silent aspiration. Patients may unknowingly reduce their oral intake and lose weight. Retrospective studies have shown that 20%-30% of patients aspirate silently (e.g. patients after stroke, acquired brain injury, head and neck cancer treatment, prolonged intubation). Clinical examination of swallowing can miss up to 50% of cases of silent aspiration. What this paper adds to existing knowledge Currently, silent aspiration is often discussed in neurological literature, but its applications to head and neck surgery are limited. In this study, we identify head and neck surgery patients who should be prioritised or considered to be in higher need of instrumental swallowing evaluation due to a higher risk of silent aspiration. What are the potential or actual clinical implications of this work? Post-treatment structural changes can result in lower cranial nerve paresis (IX, X, XII) and face injury, in which vagus and glossopharyngeal nerves are injured. After tracheostomy and radiotherapy, patients with problems swallowing saliva need careful clinical examination, particularly cranial nerve examination.

Translation and Validation of the Dysphagia Handicap Index in Polish-Speaking Patients.

Dysphagia Handicap Index (DHI) is a self-assessment questionnaire which consists of 25 statements to examine three aspects of dysphagia patients' quality of life (QoL): functional, physical, and emotional. The patient can get a maximum score of 100 points. The study goal was to validate and translate the Polish version of the DHI (PL-DHI). One hundred and seventy-eight (178) individuals with oropharyngeal dysphagia with different etiology and 35 (thirty-five) asymptomatic adults with no history of swallowing disorders filled out the PL-DHI. Internal consistency was determined using Cronbach alpha coefficient, which was high for the total PL-DHI score (0.962). The reproducibility was high (r-Spearman correlation coefficient was 0.97 for total PL-DHI score). The PL-DHI's total score and its subscales were significantly higher in the dysphagia patients study group (SG) than in the healthy controls group (CG) (SG median: 36; CG median: 4). A strong correlation was observed between the PL-DHI score and the self-reported dysphagia severity measure (Spearman's correlation coefficient was 0.859, p < 0.001). The Polish DHI is a reliable and valid questionnaire for assessing dysphagia patients' QoL.

Impact of Viewing Conditions and Vision Anomalies on Accuracy and Dynamics of Noncycloplegic Autorefraction.

SIGNIFICANCE: This study was conducted to analyze the influence of binocular vision and accommodation anomalies on refraction dynamics. Our results may help to design more accurate autorefractors and to better understand the difficulties in prescribing an optical correction or adaptation to a correction. PURPOSE: This study aimed to verify whether viewing conditions (open- or closed-field) or vision anomalies, such as ocular surface diseases, accommodative dysfunctions, and binocular vision anomalies, influence (1) the differences between subjective refraction and autorefraction and (2) the characteristics of the short-term refractive state variation. METHODS: The subjective refraction of 64 subjects aged 23 to 60 years was measured during a comprehensive optometric examination, and the Ocular Surface Disease Index questionnaire was collected. Twenty successive measurements of automated refraction of each eye were obtained using a conventional autorefractor Nidek ARK-510A and an open-field autorefractor Shin-Nippon NVision-K 5001. Conventional notation of refractive error (sphere, cylinder, axis) was transformed to h-vectors, presented in scatterplots, and analyzed statistically. RESULTS: The three-way analysis of variance tests showed that there is no influence of accommodation dysfunctions (P = .22 for ARK-510A), binocular vision anomalies (P = .97 for ARK-510A), and ocular surface diseases (P = .20 for ARK-510A) on differences between autorefraction and subjective refraction. The binocular vision anomalies affected the results from open-field autorefractor, whereas the accommodation impacted closed-field refraction measurements. Changes in short-term refractive state variation occurred in sphere power, indicating accommodative state changes; however, 30 subjects demonstrated at least one outlier and/or polymodality of refractive state distributions. CONCLUSIONS: The study showed that the presence of accommodative dysfunctions or binocular vision anomalies might increase the range of short-term refractive state variation. The impact of vision anomalies differs between viewing conditions. The polymodal distribution of refractive state variation and the presence of outliers imply that automatic modes used typically in autorefractors with three to five readings may not accurately represent the refractive state of the eye.

The Dysphagia Handicap Index (DHI)-Normative Values. Systematic Review and Meta-Analysis.

As the dysphagia handicap index (DHI) becomes more commonly used in clinical practice as a diagnostic tool, it is essential to establish the normative value of DHI. The main purpose of this study is to determine the normative value of DHI among subjects who had no history of dysphagia or neurological disease as well as no history of head or neck malignancy. A systematic literature search was performed using PubMed, Scopus and ScienceDirect to access relevant databases and to locate outcome studies. Eligibility criteria included type of publication, participant characteristics and report of outcomes. Data analysis were conducted using meta-analysis method. Five articles were included for the final analysis. The normative value of DHI was 2.49 with confidence interval of 0.51-4.48 for a group of 323 subjects, age range of 20-86 years.

Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment.

Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the α-subunit of the neuronal sodium channel Nav1.1. The syndrome is characterized by age-related progression of seizures, cognitive decline and movement disorders. We hypothesized that the distinct neurodevelopmental features in DS are caused by the disruption of molecular pathways in Nav1.1 haploinsufficient cells resulting in perturbed neural differentiation and maturation. Here, we established DS-patient and control induced pluripotent stem cell derived neural progenitor cells (iPSC NPC) and GABAergic inter-neuronal (iPSC GABA) cells. The DS-patient iPSC GABA cells showed a shift in sodium current activation and a perturbed response to induced oxidative stress. Transcriptome analysis revealed specific dysregulations of genes for chromatin structure, mitotic progression, neural plasticity and excitability in DS-patient iPSC NPCs and DS-patient iPSC GABA cells versus controls. The transcription factors FOXM1 and E2F1, positive regulators of the disrupted pathways for histone modification and cell cycle regulation, were markedly up-regulated in DS-iPSC GABA lines. Our study highlights transcriptional changes and disrupted pathways of chromatin remodeling in Nav1.1 haploinsufficient GABAergic cells, providing a molecular framework that overlaps with that of neurodevelopmental disorders and other epilepsies.

Oncological outcomes of CO2 laser cordectomies for glottic squamous cell carcinoma with respect to anterior commissure involvement and margin status.

BACKGROUND AND OBJECTIVES: Controversial prognostic factors of primary CO2 laser cordectomy are anterior commissure involvement (ACI) and status of margin. STUDY DESIGN/MATERIALS AND METHODS: Retrospective analysis of oncological outcomes in 102 patients with early glottic cancer undergoing laser cordectomy between 2013 and 2015. RESULTS: The T stages distribution included: 72.6% T1a, 14.7% T1b, and 12.7% T2. The ACI was diagnosed in 26 patients. The primary cordectomy was radical in 72 patients. The 2- and 5-year disease free survival (DFS) for all patients were, respectively, 83.3% and 77.3%.The 2-year DFS rates for T1a, T1b, T2 were, respectively, 91.7%, 66.7%, and 53.9% and the differences were statistically significant (P < 0.001). The 2-year DFS rates according to the ACI and free anterior commissure tumors were, respectively, 65.4% and 89.2%, and the ACI indicated worse prognosis (P = 0.057). The 2-year DFS rates according to margins status were higher for patients with close or positive margins, who had second resection (88.9%) compared with those of negative margins (80.9%) (P = 0.340). Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Laryngeal stroboscopy-Normative values for amplitude, open quotient, asymmetry and phase difference in young adults.

OBJECTIVE: To provide the normative values for laryngeal stroboscopy (LS) concerning amplitude, open quotient, asymmetry and phase difference in healthy, young subjects. STUDY DESIGN: Prospective case-control study. SETTING: Patients treated at a single institute. METHODS: A total of 68 healthy subjects were included in the study (35 women, 33 men), aged 18-35 years. After obtaining LS recordings, image processing was performed to attain parameters of vocal fold vibration. RESULTS: In women, the location of the maximum vibration amplitude is approximately in the 1/3 posterior part of the glottis, while in men, the location is moved to the glottis centre. In males, the relative amplitude vibration of the vocal folds in the 1/3 anterior part of the glottis was significantly higher than in females (P = 0.029). Women showed significantly higher open quotients (OQ) at the posterior part of the glottis than the male subjects (P < 0.001) and men presented significantly higher OQ at the anterior part of the glottis than the females (P < 0.001). The average OQ values for both sexes were almost the same. Females showed significantly higher relative glottal gap area (P = 0.044). Women presented a significantly lower amplitude asymmetry than men (P = 0.002). The weighted absolute left-right phase difference reached up to 24° and remained insignificantly higher in the men than the women (P = 0.142). CONCLUSIONS: The study provides normative values for LS in young adults for the measurement of therapy outcomes in patients with voice disorders and realisation of evidence-based medicine. The LS parametrisation is easy to perform in clinical practice.

Changes in leukocyte profile and C-reactive protein concentration in overweight and obese adolescents after reduction of body weight.

AIM OF THE STUDY: To assess the changes in the leukocyte profile and C-reactive protein (CRP) concentration in adolescents with excess fat mass after 6-12 months of dietary intervention. MATERIAL AND METHODS: The retrospective study included 99 overweight and obese adolescents, aged from 10.0 to 17.5 years, 82 of whom were re-hospitalized 6 to 12 months after dietary counseling. The control group consisted of 42 normal weight peers. Anthropometric measurements and laboratory tests were performed, homeostasis model assessment - insulin resistance (HOMA-IR) and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio were calculated. RESULTS: Obese and overweight adolescents had higher white blood cells (WBC), neutrophil, monocyte counts and CRP concentration. In the backward stepwise regression analysis, body mass index standard deviation score (BMI SDS) and fasting insulin concentration were independent predictors of WBC and neutrophil counts at the baseline. At the follow-up visit in 45 (54.8%) children, who had lost weight, decreases in WBC, neutrophil and monocyte counts and CRP, fasting insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) concentrations were observed. Changes in WBC and neutrophil counts were dependent on changes in HOMA-IR and TG/HDL ratio. Changes in HOMA-IR had a significant impact on changes in the monocyte count. CONCLUSIONS: Adipose tissue promotes systemic inflammation and its intensity depends on the degree of obesity and insulin resistance. This state is reversible. Changes in HOMA-IR were independent predictors of changes in WBC, neutrophil and monocyte counts after reduction of body weight.

Osteoprotegerin, Receptor Activator of Nuclear Factor Kappa B Ligand, and Growth Hormone/Insulin-Like Growth Factor-1 Axis in Children with Growth Hormone Deficiency.

The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is involved in the regulation of the receptor activator of nuclear factor kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system, but the exact mechanism of the associations is not fully explained. In this study we investigated the serum OPG and total sRANKL concentrations in short children who had differences in GH secretory status. We also investigated the associations between the GH/IGF-1 and OPG/RANKL systems in GH-deficient children during GH treatment. There were no significant differences in any anthropometric or biochemical parameters evaluated between the GH-deficient and GH-sufficient children. The OPG content and total alkaline phosphatase (ALP) activity increased significantly after the initiation of GH treatment, while total sRANKL remained unchanged. The variables baseline BMI SDS for height-age (ß = 0.42; p < 0.05), baseline ALP activity (ß = 0.36; p < 0.05), weight SDS for height-age at 6 months of GH treatment (ß = 1.86; p < 0.01), and total ALP activity at 6 months of GH treatment (ß = 0.48, p < 0.01) were identified as independent predictors of ΔOPG6-month-baseline. We conclude that OPG and total sRANKL concentrations are independent from GH secretory status in short children. OPG elevation during GH treatment is independently associated with total ALP activity and nutritional status in GH-deficient children.

Thyroid function in children with growth hormone deficiency during long-term growth hormone replacement therapy.

AIM OF THE STUDY: The aim of this study was to investigate the effects of growth hormone (GH) therapy on thyroid function in a group of euthyroid children with isolated idiopathic growth hormone deficiency (GHD). MATERIAL AND METHODS: The study was retrospective and included 117 children treated with GH for 1-4 years. Anthropometric measurements and serum concentrations of insulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) were analysed at baseline and during GH therapy. RESULTS: TSH levels did not change significantly after the initiation of GH treatment, while fT4 levels decreased after the second year of GH treatment (p < 0.01) and remained lower than baseline until the end of observation (p < 0.01, after both the third and fourth year of therapy) in the whole group. Analysis according to baseline pubertal status revealed significant changes in TSH and fT4 levels during GH treatment, but only in the prepubertal children. Multiple regression analysis confirmed that mean GH doses administered in the first two years of GH therapy were independently (R = 0.218, p < 0.05) associated with changes in fT4 levels in this period (∆fT42 years - baseline), even when taking into account changes in height SDS and bone age. CONCLUSIONS: FT4 levels decreased during GH replacement therapy, while TSH levels appeared to be unaffected by GH therapy. Prepubertal children seem to be more predisposed to thyroid function alterations during such therapy in comparison to pubertal children. Changes in fT4 levels during GH replacement therapy are related to GH doses.

The differential diagnosis of parotid gland tumors with high-resolution ultrasound in otolaryngological practice.

The aim of the study is to define the utility of ultrasound (US) in differentiating benign from malignant parotid tumors as well as pleomorphic adenomas (PA) from monomorphic adenoma (MA). Seventy-two consecutive parotid gland tumors were analysed with high-resolution ultrasonography (12 MHz) with color Doppler imagining. The histopathological diagnosis was confirmed after parotidectomy for each lesion. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for the US were established. Receiver operating characteristic curves were constructed to determine the predictive values of echogenicity, heterogeneity, and vascularity on color Doppler. Area under the curve (AUC) was calculated for each parameter considered. The analysed material included 27 MA, 26 PA, 1 basal cell adenoma, 8 inflammatory conditions, and 10 malignant neoplasms. The sensitivity, specificity, and accuracy of US in differentiation of malignant from benign lesions in the parotid gland were 60, 95.2, and 90.3%, respectively. The predictive values were: PPV 66.8% and NPV 93.6%. Differentiating diagnoses between PA and MA with US resulted in a sensitivity of 61.5%, specificity of 81.5%, and accuracy of 73.1%. The predictive values were: PPV 50% and NPV 68.8%, respectively. For distinguishing malignant from benign tumors, the highest AUC values noted were for heterogeneity and vascularization (0.8 and 0.743, respectively). The AUC values were the highest for hypoechogenicity and vascularization in separating PA from MA (0.718 and 0.685, respectively).

The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women.

AIM OF THE STUDY: Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status. MATERIAL AND METHODS: Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. RESULTS: Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (-) tumours. CONCLUSIONS: Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics.

Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia.

Inherited and isolated nail malformations are rare and heterogeneous conditions. We identified two consanguineous pedigrees in which some family members were affected by isolated nail dysplasia that suggested an autosomal-recessive inheritance pattern and was characterized by claw-shaped nails, onychauxis, and onycholysis. Genome-wide SNP array analysis of affected individuals from both families showed an overlapping and homozygous region of 800 kb on the long arm of chromosome 8. The candidate region spans eight genes, and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes and differentiation through several signaling pathways. We expressed the FZD(6) missense mutation and observed a quantitative shift in subcellular distribution from the plasma membrane to the lysosomes, where the receptor is inaccessible for signaling and presumably degraded. Analysis of human fibroblasts homozygous for the nonsense mutation showed an aberrant response to both WNT-3A and WNT-5A stimulation; this response was consistent with an effect on both canonical and noncanonical WNT-FZD signaling. A detailed analysis of the Fzd(6)(-/-) mice, previously shown to have an altered hair pattern, showed malformed claws predominantly of the hind limbs. Furthermore, a transient Fdz6 mRNA expression was observed in the epidermis of the digital tips at embryonic day 16.5 during early claw morphogenesis. Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways.

Intraocular Pressure (IOP) in Patients with Acromegaly versus Healthy Controls: A Systematic Review and Meta-Analysis.

PURPOSE: Acromegaly is an uncommon condition but affects numerous organ systems. It has been found that patients with acromegaly can experience ocular changes, such as raised intraocular pressure (IOP). Numerous studies have since been carried out to determine whether there is a significant difference between IOP in patients with acromegaly and healthy controls and there is much disagreement in the literature. This study aims to perform a systematic review and meta-analysis to establish whether there is a significant difference in IOP between the two groups in a larger population. METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science to access relevant databases and to locate outcome studies. Eligibility criteria included type of publication, participant characteristics, and report of outcomes. Data analysis was conducted with a fixed-effects model. RESULTS: Three articles were included in the final analysis. The mean value of IOP corrected for central corneal thickness (IOPcc) for the group of 102 patients with acromegaly was 15.33 with confidence levels of 13.05-17.62 [mmHg]. The mean difference between the control and acromegaly group was 1.17 with confidence levels of 0.64 to 1.70 [mmHg], which was found to be statistically significant (p < 0.001). CONCLUSION: The results of the meta-analysis indicate that acromegaly is associated with increased IOP. As raised IOP is a risk factor for the development of glaucoma, detailed IOPcc evaluation should be an important procedure in the follow-up visits of patients with acromegaly.

The Rhinoplasty Outcome Evaluation (ROE) Questionnaire in Rhinoplasty: A Systematic Review and Meta-Analysis.

Background/Objectives: This study aims to systematize the ability to use ROE to assess rhinoplasty outcomes in surgical approaches. Methods: The PubMed, Scopus, and Web of Science databases were searched for the following terms: "rhinoplasty and outcome" OR "prognosis" OR "outcomes" OR "satisfaction" OR "quality of life" OR QoL "rhinoplasty outcome evaluation". The timeframe of the included studies is from 2011 to May 2024. Ultimately, 17 papers were included in the conducted meta-analysis of ROE scores between pre- and post-treatment data. Results The mean value of the pre-treatment ROE score was 33.50 with a CI of 29.46 to 37.53 (p < 0.001), while the post-treatment ROE was 69.60 with a CI of 63.07 to 76.14 (t ≤ 6 months). At t = 12 months it was 80.25 with a CI of 75.79 to 84.70 (p < 0.001). The mean difference between pre-treatment and post-treatment scores (t ≤ 6 months) was -36.31 with a CI of -40.93 to -31.69. The mean difference between pre-treatment and post-treatment scores for 6 m < t ≤ 12 m was -47.36 with a CI of -53.89 to -40.83. Conclusions: The result was statistically significant (p < 0.001).

Changes in Maxillary Sinus Volume and Mucosal Thickness Post Bimaxillary Advancement Procedures: A Retrospective Study.

Background: Bimaxillary surgery is an elemental procedure in the field of cranio-maxillofacial surgery. It allows for the correction of even the most challenging cases of maxillomandibular disorders, malocclusion, facial asymmetry, and disproportion. The osteotomies and maneuvers carried out during the procedure result in changes to the surrounding tissues, including the maxillary sinuses (MS). The aim of this study was to assess the change in the maxillary sinus volume and the thickness of the mucosa after maxillomandibular advancement (MMA) surgeries. Methods: A group of 25 patients who underwent MMA surgery were included in the study. Computed tomography (CT) of the head and neck region was performed 2 weeks preoperatively and 6 months postoperatively. Acquired Digital Imaging and Communications in Medicine (DICOM) files were analyzed using different software programs to calculate the medium MS mucosa thickness and MS volume. Results: A statistically significant reduction in MS volume was observed (p = 0.015). The change in the median thickness of the MS mucosa was not statistically significant. The median sella-nasion-A point angle (SNA angle) value of the group increased from 80.2 to 83.4 degrees. A weak negative correlation between the SNA delta and the MS volume delta was observed. Spearman's rank coefficient: (ρ s = -0.381, p = 0.060). Conclusions: The MMA surgery results in a reduction in the MS volume. The amount of forward movement of the maxilla may be correlated with the extent of the MS volume reduction.

Generation of a ZEB2 deficient human iPSC line (KICRi002A-4).

The transcription factor ZEB2 is essential for early embryonic development. Using CRISPR/Cas9, we generated a ZEB2 deficient human iPSC cell line (KICRi002A-4), carrying a homozygous 790 bp deletion in ZEB2 that involves part of exon 5, intron 5 and part of exon 6. The deletion leads to markedly reduced levels of a truncated ZEB2 transcript. No ZEB2 protein was detected by immunopreciptation. The iPSC line expressed pluripotency markers and showed a capacity to differentiate into the three germ layers in vitro. Assessment of genomic integrity revealed a normal karyotype without detectable OFF-target editing. The iPSC line KICRi002A-4 thus offers a valuable resource to study the role of ZEB2 for the commitment and differentiation of various human cell lineages.

The Assessment of Upper Airway Volume Changes Following Bimaxillary Advancement Surgery: A Radiological Evaluation in the Supine Position at Multiple Intervals.

Background: Bimaxillary surgeries (BiMax) are an essential part of the craniomaxillofacial specialty. The osteotomies and subsequent spatial rearrangement of the maxilla and the mandible enable the correction of facial deformities, asymmetry, and malocclusion. Moreover, the movements performed during the procedure affect the morphology of surrounding soft tissues, including the upper airway (UA). Objectives: The objective of this study was to radiologically assess the potential volumetric alterations of the UA in the supine position at various intervals following BiMax advancement surgeries. Methods: A group of 31 patients who underwent BiMax advancement surgery were included in the study. Medical computed tomography (CT) of the head and neck region was performed 2 weeks preoperatively, 1 day postoperatively, and 6 months postoperatively. The UA volumes were calculated and analyzed based on the acquired Digital Imaging and Communications in Medicine (DICOM) files using different software applications. The sella-nasion-A point (SNA) and sella-nasion-B point (SNB) angles were evaluated to measure the achieved maxillomandibular advancement. Results: When comparing the volume of the UA before surgery, post-surgery, and 6 months post-surgery, the p-value was <0.001, indicating statistically significant differences in UA volume between the successive examinations. A statistically significant difference was found between UA volume before surgery and 6 months post-surgery and between UA volume after surgery and 6 months post-surgery, with the obtained p-values being <0.001 and 0.001, respectively. A significantly larger UA volume was observed 6 months post-surgery (mean ± SD: 27.3 ± 7.3) compared to the volume before surgery (mean ± SD: 22.2 ± 6.4), as well as 6 months post-surgery compared to the volume assessed shortly after surgery (mean ± SD: 24.2 ± 7.3). Conclusions: BiMax advancement surgeries result in the significant enlargement of the UA. The volume of the UA does not diminish immediately following the procedure and is not constant; it increases significantly during the postoperative observation period.

Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases. Material and methods: The immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies. Results: All patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes. Conclusions: There is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing.

Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness, which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM-associated haplotype followed by whole exome sequencing. Within the conserved haplotype, we identified a single heterozygous mutation c.1150G>A (p.E384K) in T-cell intracellular antigen-1 (TIA1) in all WDM patients investigated (n = 43). The TIA1 protein regulates splicing, and translation through direct interaction with mRNA and the p.E384K mutation is located in the C-terminal Q-rich domain that interacts with the U1-C splicing factor. TIA1 has been shown to prevent skipping of SMN2 exon 7, and we show that WDM patients have increased levels of spliced SMN2 in skeletal muscle cells when compared with controls. Immunostaining of WDM muscle biopsies showed accumulation of TIA1 and stress granulae proteins adjacent to intracellular inclusions, a typical finding in WDM. The combined findings strongly suggest that the TIA1 mutation causes perturbed RNA splicing and cellular stress resulting in WDM. The selection against the mutation is likely to be negligible and the age of the TIA1 founder mutation was calculated to approximately 1,050 years, which coincides with the epoch of early seafaring across the Baltic Sea.