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Background Dysphagia is a geriatric syndrome. Changes in the whole body that occur with aging also affect swallowing functions and cause presbyphagia. This condition may progress to oropharyngeal and/or esophageal dysphagia in the presence of secondary causes that increase in incidence with aging. However, no study has been published that provides recommendations for use in clinical practice that addresses in detail all aspects of the management of dysphagia in geriatric individuals. This study aimed to answer almost all potential questions and problems in the management of geriatric dysphagia in clinical practice. Methods A multidisciplinary team created this recommendation guide using the seven-step and three-round modified Delphi method via e-mail. The study included 39 experts from 29 centers in 14 cities. Results Based on the 5W and 1H method, we developed 216 detailed recommendations for older adults from the perspective of different disciplines dealing with older people. Conclusion This consensus-based recommendation is a useful guide to address practical clinical questions in the diagnosis, rehabilitation, and follow-up for the management of geriatric dysphagia and also contains detailed commentary on these issues.

Objective:To investigate the prognostic value of the magnetic resonance imaging in Bell’s palsy patients.Methods:Patients who were diagnosed and treated with Bell’s palsy between October 2013 and March 2016 retrospectively selected. House–Brackmann grades, pre- and post-treatment pure tone audiograms, stapedial reflexes were analyzed and magnetic resonance imaging (MRI) scans with gadolinium-based contrast agents were evaluated. Contrast-enhanced segments of the facial nerve were determined. MRI findings were compared statistically with pre- and post-treatment grade, recurrence rate of Bell’s palsy, MRI scanning timing, presence of stapes reflexes and posttreatment recovery data.Results:No significant correlation was observed between pretreatment House–Brackmann grades and enhancement (p>0.05). Similarly, there was no significant correlation between clinical recovery and enhancement (p>0.05). Also, no significant correlation was observed between MRI scanning time, the recurrence rate of Bell’s palsy and MRI findings (p>0.05). None of the MRIs showed neoplastic contrast enhancement.Conclusion:The routine use of the contrast-enhanced temporal MRI is not recommended in the diagnosis and monitoring of Bell’s palsy patients, because the contrast enhancement pattern of the facial nerve has no effect on the prognosis of Bell’s palsy. MRI should be used in cases that do not heal despite treatment, for the differential diagnosis of facial nerve tumors and in patients who are candidates for surgical decompression.

Summary: Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pattern formation is reproducibly executed despite these unavoidable fluctuations in gene expression. Here, we studied the transcriptional variability of two paired zebrafish segmentation clock genes (her1 and her7) in multiple genetic backgrounds. Segmentation clock genes establish an oscillating self-regulatory system, presenting a challenging yet beautiful system in studying control of transcription variability. In this study, we found that a negative feedback loop established by the Her1 and Her7 proteins minimizes uncorrelated variability whereas gene copy number affects variability of both RNAs in a similar manner (correlated variability). We anticipate that these findings will help analyze the precision of other natural clocks and inspire the ideas for engineering precise synthetic clocks in tissue engineering.

The aim of this case report is to demonstrate a very rare coincidental existence and management of the Killian- Jamieson diverticulum during thyroid surgery in a patient with dysphagia. An 18-year-old female patient with the complaints of progressive dysphagia and a rapidly growing mass at the anterior cervical region was undergone thyroid lobectomy. Coincidentally, a 2×2 cm Killian-Jamieson diverticulum was observed and simultaneously excised with the thyroid lobe, preserving the recurrent laryngeal nerve. Dysphagia is a frequent symptom, especially in patients with a rapidly growing thyroid mass. Thyroid surgeons should keep in mind that hypopharyngeal and upper esophageal pathologies can mimic the symptoms of a thyroid mass; therefore, detailed imaging techniques should be used for the differential diagnosis.

Self-assembly of 13 nm gold nanoparticles (AuNPs) engineered into 2D structures in solution using DNA tiles for their possible use for gene delivery and photothermal therapy is reported. The two different DNA tiles were constructed and the AuNPs coated with oligonucleotides possessing complementary sequence from the free ends were hybridized with the sticky ends of the tiles. The DNA tiles were bind to each other by mixing the tile structures without a heating and cooling step. The constructed nanostructures were 5 to 7 DNA tiles long since heat was not used to elongate them. When the DNA tiles were bound to the AuNPs, it was observed that AuNPs tend to stay in close proximity by filling the gaps between tiles. The stability of the constructed structures was tested against DNase, a DNA cleaving enzyme, for possible applications for gene delivery and photothermal therapy. It was found that the AuNP bound DNA tile structures resist the DNase cleavage up to eighty percent. Due to the presence of the AuNPs in the structure, the enzyme cannot bind to DNA sequences and this increases the DNA tile structures’ stability.

Objetivo: Comparar e investigar los parámetros de la tomografía de coherencia óptica (OCT) de los lados sanos y afectados de pacientes con pérdida auditiva neurosensorial súbita idiopática (PANSI). Método: La evaluación ocular bilateral de los pacientes diagnosticados con PANSI se realizó con OCT. Se registraron los valores de espesor del complejo de células ganglionares (CCG) y de la capa de fibras nerviosas de la retina (CFNR), y se examinaron las diferencias entre los dos ojos. Resultados: Se evaluaron 39 pacientes, con una edad media de 44.82 ± 14.90 años. Se determinó que el grosor de la CFNR de los ojos era una media de 89.87 ± 3.65 μm en el lado afectado y 103.87 ± 3.98 μm en el lado de control sano (p = 0.0001). Se determinó que el CCG medio era 90.46 ± 3.49 μm en el lado afectado y 103.77 ± 3.96 μm en el lado de control sano (p = 0.0001). Conclusiones: Se encontró una diferencia estadísticamente significativa entre los ojos sanos y afectados de pacientes con PANSI con respecto al CCG medio y al espesor medio de la CFNR. La OCT podría ser una técnica útil para medir esta degeneración neuronal.

Abstract Background/Objectives Rare genetic disorders causing specific congenital developmental abnormalities often manifest in single families. Investigation of disease-causing molecular features are most times lacking, although these investigations may open novel therapeutic options for patients. In this study, we aimed to identify the genetic cause in an Iranian patient with severe skeletal dysplasia and to model its molecular function in zebrafish embryos. Results The proband displays short stature and multiple skeletal abnormalities, including mesomelic dysplasia of the arms with complete humero-radio-ulna synostosis, arched clavicles, pelvic dysplasia, short and thin fibulae, proportionally short vertebrae, hyperlordosis and mild kyphosis. Exome sequencing of the patient revealed a novel homozygous c.374G > T, p.(Arg125Leu) missense variant in MSGN1 (NM_001105569). MSGN1, a basic-Helix–Loop–Helix transcription factor, plays a crucial role in formation of presomitic mesoderm progenitor cells/mesodermal stem cells during early developmental processes in vertebrates. Initial in vitro experiments show protein stability and correct intracellular localization of the novel variant in the nucleus and imply retained transcription factor function. To test the pathogenicity of the detected variant, we overexpressed wild-type and mutant msgn1 mRNA in zebrafish embryos and analyzed tbxta (T/brachyury/ntl). Overexpression of wild-type or mutant msgn1 mRNA significantly reduces tbxta expression in the tailbud compared to control embryos. Mutant msgn1 mRNA injected embryos depict a more severe effect, implying a gain-of-function mechanism. In vivo analysis on embryonic development was performed by clonal msgn1 overexpression in zebrafish embryos further demonstrated altered cell compartments in the presomitic mesoderm, notochord and pectoral fin buds. Detection of ectopic tbx6 and bmp2 expression in these embryos hint to affected downstream signals due to Msgn1 gain-of-function. Conclusion In contrast to loss-of-function effects described in animal knockdown models, gain-of-function of MSGN1 explains the only mildly affected axial skeleton of the proband and rather normal vertebrae. In this context we observed notochord bending and potentially disruption of pectoral fin buds/upper extremity after overexpression of msgn1 in zebrafish embryos. The latter might result from Msgn1 function on mesenchymal stem cells or on chondrogenesis in these regions. In addition, we detected ectopic tbx6 and bmp2a expression after gain of Msgn1 function in zebrafish, which are interconnected to short stature, congenital scoliosis, limb shortening and prominent skeletal malformations in patients. Our findings highlight a rare, so far undescribed skeletal dysplasia syndrome associated with a gain-of-function mutation in MSGN1 and hint to its molecular downstream effectors.

Abstract Mutations of several genes cause incomplete penetrance and variable expressivity of phenotypes, which are usually attributed to modifier genes or gene-environment interactions. Here, we show stochastic gene expression underlies the variability of somite segmentation defects in embryos mutant for segmentation clock genes her1 or her7. Phenotypic strength is further augmented by low temperature and hypoxia. By performing live imaging of the segmentation clock reporters, we further show that groups of cells with higher oscillation amplitudes successfully form somites while those with lower amplitudes fail to do so. In unfavorable environments, the number of cycles with high amplitude oscillations and the number of successful segmentations proportionally decrease. These results suggest that individual oscillation cycles stochastically fail to pass a threshold amplitude, resulting in segmentation defects in mutants. Our quantitative methodology is adaptable to investigate variable phenotypes of mutant genes in different tissues.

Summary: Taming gene expression variability is critical for robust pattern formation during embryonic development. Here, we describe an optimized protocol for single-molecule fluorescence in situ hybridization and immunohistochemistry in zebrafish embryos. We detail how to count segmentation clock RNAs and calculate their variability among neighboring cells. This approach is easily adaptable to count RNA numbers of any gene and calculate transcriptional variability among neighboring cells in diverse biological settings.For complete details on the use and execution of this protocol, please refer to Keskin et al. (2018),1 Zinani et al. (2021),2 and Zinani et al. (2022).3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Introduction:. The gap junction beta 6 (GJB6) gene encodes connexin 30. This protein plays critical role in tissues and is responsible for the formation of gap junctions, which have a wide variety of physiological functions. Disease-associated variants of GJB6 cause non-syndromic hearing loss (HL) and skin lesions. We herein describe a Turkish girl who was diagnosed with HL and in whom genetic analysis revealed a causal variant of GJB6. Case presentation:. The 1-year-old girl patient was diagnosed with bilateral HL when she was 1 month old. Apart from this, the patient’s motor/mental development and physical examination were normal. As a result of the analysis with the multi-gene panel, the causative genomic change, c.175G>A(p.Gly59Arg) in the GJB6 gene was determined as heterozygous. Segregation analysis proved the same genotype in the patient’s mother and grandfather. The patient’s mother and grandfather had bilateral HL and palmoplantar hyperkeratosis phenotype. The patient was diagnosed with Clouston syndrome, and genetic counseling was provided to her family. Discussion:. Causal variants of GJB6 cause skin manifestations and signs of HL. Molecular diagnosis of these patients is a valuable tool for clinicians in reaching their optimal treatment and clinical management. Conclusion:. In syndromic cases in which many organs are affected, the determination of the causative gene is important in directing the patients to appropriate observation, screening, and treatment strategies.

Introduction Vestibular otolith function plays a major role in balance control. Objective To investigate the saccular and balance functions of children with Down syndrome (DS). Methods In total, 15 children with DS aged between 9 and 11 years were included. An age- and gender-matched control group (CG) composed of 15 normal participants was also included. The subjects with DS had trisomy 21, without hearing or organic problems, and they had independence in stance. The saccular function among the children with DS and among the controls was tested using air-conduction cervical vestibular-evoked myogenic potentials (cVEMPs). In addition, the static and dynamic balance statuses were evaluated using the following assessments; the Pediatric Balance Scale (PBS), the modified Clinical Test of Sensory Interaction on Balance (mCTSIB), the Romberg test, and the Timed Up and Go (TUG) test. Results In the present study, the results of the saccular function test showed that there was a significant difference between children with and without DS (p